\r\n\t1. Emphasizing the unique power of the molecular docking method in new drug discovery; \r\n\t2. Demonstration of how the molecular docking technique has led to the discovery of new molecules in cancer therapy, proteasome, and STAT3 inhibition, and the treatment of Alzheimer's disease; \r\n\t3. Underlining the importance of molecular docking-based modeling methods in the various branches of biotechnology
\r\n
\r\n\tWe hope that this book will be a common point where researchers working in the fields of life sciences and drug development will eventually meet.
",isbn:"978-1-80356-468-5",printIsbn:"978-1-80356-467-8",pdfIsbn:"978-1-80356-469-2",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"8c918a1973786c7059752b28601f1329",bookSignature:"Dr. Erman Salih Istifli",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11451.jpg",keywords:"Protein-Ligand Interaction, Lead Discovery, Molecular Recognition, Enzyme-Ligand Interaction, Mutant Enzymes, Alanine Screening, Proteasome Inhibitors, Signal Transducers, Transcription Activators (STATs), DNA Recognition Motifs, Neoplastic Cells, Amyloid-Beta Proteins",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 3rd 2022",dateEndSecondStepPublish:"May 4th 2022",dateEndThirdStepPublish:"July 3rd 2022",dateEndFourthStepPublish:"September 21st 2022",dateEndFifthStepPublish:"November 20th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A multidisciplinary researcher working in the fields of cytogenetics, molecular genetics, and bioinformatics-based molecular modeling (currently on the structural biology of COVID-19 and the treatment of Alzheimer’s disease). 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1. Introduction
Diabetes is a global threat that affects the quality of life, and it is estimated that it will affect 220 million people by the year 2020 worldwide. Morbidity and mortality in diabetic patients are caused by infections. Evidence suggests that, urinary tract infection (UTI) is the most common bacterial infections among diabetic patients. According to American Diabetes Association (ADA) report, patients suffering from type 2 diabetes are more likely to have a urinary tract infection (UTI) and repeat UTI than patients without diabetes. Symptomatic bacteriuria in patients with diabetes is serious and warrants proper clinical attention for diagnosis and treatment. High glucose concentration in the urine can provide a rich source of nutrients for bacteria. Therefore, bacteria can multiply and make foundation for infection also. High glucose concentration in the urine can allow urinary colonization by microorganisms. Moreover, multiple mechanisms were involved in UTI patients with diabetes. Diabetic female, diabetic overweight, and diabetic obese patients are having the highest risk of UTI. In general diabetic population, other risk factors associated with urinary tract infection were found to be diabetic nephropathy, diabetes with hypertension, and insulin therapy. Emphysematous pyelonephritis, emphysematous cystitis, renal and perinephric abscesses, urosepsis, and bacteremia are the complications of diabetes-associated UTI. Longer hospitalization, recurrence of UTI, relapse and re-infection, bacteremia, azotemia, and septic shock are the outcomes of diabetes-associated UTI [1].
2. Diabetes
Diabetes is a persistent disease. This disease is characterized by increase of blood glucose level. The reasons of increase of blood glucose level may be either insufficient production of insulin, a hormone that regulates the blood glucose level, or the insulin produced cannot be used properly. Frequent urination, increased thirst, and increased hunger are the common symptoms of diabetes. Uncontrolled blood sugar level can cause many complications. These complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the eyes, diabetic ketoacidosis, etc. Diabetes mellitus can be described as group of metabolic disorders causing increase in blood sugar level due to defect in insulin secretion, insulin action, or both [2]. The digestive system breaks carbohydrates, sugars, and starches found in many foods into glucose, which is a type of sugar that enters the bloodstream [3]. By the action of the hormone insulin, cells throughout the body absorb glucose and use it for energy. Diabetes develops when the body does not produce enough insulin or is unable to use insulin effectively or both. Insulin is produced in the pancreas. Clusters of cells found in the pancreas are called islets. Pancreas having islets, which contain beta cells, produces insulin and releases it into the blood.
3. Types of diabetes
Type 1 diabetes also called as insulin-dependent diabetes mellitus (type I diabetes occurs due to β-cell destruction, usually leading to absolute insulin deficiency).
Type 2 diabetes also called as noninsulin-dependent diabetes mellitus (type II diabetes occurs due to a progressive loss of insulin secretion).
Gestational diabetes mellitus (GDM) (diabetes detected in the second or third trimester of pregnancy that is not clearly overt diabetes).
Specific types of diabetes due to other reasons, for example, monogenic diabetes syndromes (such as maturity-onset diabetes of the young [MODY] and neonatal diabetes), diseases associated with exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced diabetes (such as use of glucocorticoid, in the treatment of HIV/AIDS or after organ transplantation).
Type 1 diabetes occurs in childhood, mainly due to destruction of pancreatic β-cell islets through autoimmune-mediated, causing complete insulin deficiency. Type 2 is more associated with adults and elderly people, which are mainly due to insulin resistance or abnormal insulin production. The exact reason of pancreatic failure and insulin resistance is unknown, but they are associated with disease condition, food habit, and environmental impact. Diabetic patients are more susceptible to various type of infection such as skin diseases and carbuncles [4].
Gestational diabetes is other type of diabetes, which is mainly associated with pregnancy. It occurs in the 4% of pregnancies in US, usually during the third trimester. It causes increased perinatal morbidity and mortality unless properly diagnosed or managed. Genetic defects of β-cell function or insulin action is also a type of diabetes mellitus commonly called maturity onset diabetes. Neonatal diabetes mellitus is also a type of diabetes, in which first 3 months of life insulin is required for the maintenance of blood glucose level in. It may be caused by intrauterine growth retardation and defects of chromosome. The heart, blood vessels, eyes, kidneys, and nerves can be damaged by diabetes, leading to disability and premature death.
4. Urinary tract infection in diabetics
Infections are frequent causes of morbidity and mortality in diabetic patients. Evidence suggesting that urinary tract infection (UTI) is the most common bacterial infections among diabetic patients. High glucose concentration in the urine can provide a rich source of nutrients for bacteria [5, 6]. Therefore, bacteria can multiply and make foundation for infection; also, high glucose concentration in the urine can allow urinary colonization by microorganisms. Moreover, some of the immunological defects like impaired neutrophil function, reduced T cell-mediated immune response, low levels of prostaglandin E, thromboxane B2, and leukotriene B4 may contribute to the increased risk for infection. Other conditions such as bladder dysfunction (incomplete bladder emptying) caused by autonomic neuropathy also may contribute to the increased risk for infection [7, 8]. UTI in diabetes can lead to severe complications including bacteremia, renal abscess, and renal papillary necrosis. In some cases, diabetes modifies the genitourinary system and may cause damage to the organ, which leads to pyelonephritis. This type of UTI occurs 15 times more frequently in diabetic patients. Therefore, early diagnosis and correct treatment are very important for diabetes patients with UTI [9, 10]. Molecular reasons for an increased frequency of UTI in diabetic patients include depression in the function of polymorphonuclear leucocytes especially during acidosis, dysfunction of chemotaxis, and phagocytosis [10]. High blood glucose levels may cause nerve damage, affecting the ability of the bladder to sense the presence of urine and thus allowing urine to stay for a long time in the bladder and increasing probability of infection [11].
Various types of UTI in patients with diabetes include
Asymptomatic bacteriuria
Acute cystitis
Complicated lower UTI (including catheter-associated UTI)
Uncomplicated pyelonephritis
Complicated pyelonephritis/urosepsis
5. Pathogenesis of UTI in diabetics
The chance of occurrence of UTIs in diabetic patients used to increase many folds due to several factors. Multiple potential mechanisms unique to diabetes may cause increased risk of UTI in diabetic patients. Elevated renal parenchymal glucose levels create a positive environment for the growth and multiplication of microorganisms, which is one of the precipitating factors of pyelonephritis and renal problem such as emphysematous pyelonephritis. Several problems in the immune system, including humoral, cellular, and innate immunity, may help in the pathogenesis of UTI in diabetic patients [12, 13, 14]. Lower urinary interleukin-6 and interleukin-8 levels were found in diabetic patients with UTI. An outline of process involved in pathogenesis of urinary tract infection in diabetic patients is mentioned in Figure 1.
Figure 1.
Process involved in pathogenesis of UTI in patients with diabetes.
Some suggested host related mechanisms include [15]:
Presence of glycosuria
Increased adherence to uroepithelial cells
Immune dysfunction
5.1. Presence of glycosuria
The presence of glycosuria is responsible for the growth of different microbial strains. Among all E. coli is the major cause for the condition of UTI [15]. The bacteria isolated from diabetic patients with a UTI are similar to the bacteria found in nondiabetic patients with a complicated UTI. As in uncomplicated UTIs, E. coli causes the majority of infections. For example, one study reported E. coli to be the causative uropathogen in 47% of the UTIs in diabetic patients and in 68% of the UTIs in nondiabetic patients. Non-E. coli uropathogens found in patients with diabetes, include Enterobacter spp., Klebsiella spp., Proteus spp., Group B Streptococci, and Enterococcus faecalis [16].
Geerlings et al. [17] in their study reported that urine samples with glucose concentrations between 100 and 1000 mg/dL, which comes in the range of moderate to severe glucosuria, were responsible for enhanced bacterial growth after 6 h, compared with normal urine.
E. coli gain access to the urinary tract by the mechanism which reflects an exceptional ability to adapt to an environment very different from the gut. They need to alter their metabolism [18], ascend against the flow of urine, and adhere to the epithelial layer. E. coli that successfully invade the urinary tract harbor a specific factor that enables them to survive. These strains of E. coli are commonly named uropathogenic E. coli (UPEC). Flagellae are thread-like structures which provide E. coli with the ability to move. It has been found to bind to TLR5 [19] and is of importance for the immune response to E. coli in UTI in mice [20]. A critical step for UPEC is adhesion to avoid being washed out with the urine and the first step in a series of events leading to infection. The type-1 fimbriae are adhesion factors studied in great detail and are critical for adhesion and invasion of UPEC into bladder cells [21, 22]. They are equipped with a protein on the tip called FimH, which is responsible for the interaction with the host cell [23]. It binds to several structures on uroepithelial cells, the most important being uroplakin IA that coats the facet cells of the bladder [24]. They also bind to β-integrin, which triggers cytoskeleton rearrangement leading to bacterial internalization [25]. In renal epithelial cells, complement factor 3, which is secreted by epithelial cells during infection, can link with type 1 fimbriae to form a complex that interacts with CD46 to promote internalization. Other fimbriae like P fimbriae are connected with kidney infection, since they bind to glycosphingolipids on kidney epithelial cells [26].
Flagella provide the bacteria with mobility and may interact with the superficial bladder cell through TLR5. Further adhesion is provided by type 1 fimbriae binding to uroplakin 1A or β1-integrin, which also promote internalization into the cell. Complement secreted upon bacterial infection binds to the bacteria and promotes interaction with the bladder through CD46. In the kidney, P fimbriae of the bacteria bind to glycosphingolipids on the surface of renal epithelial cells. Bacterial invasion is further promoted by TLR4 and TLR5.
5.2. Increased adherence to uroepithelial cells
The uroepithelium is having a very important property of flexibility by which it will allow filling and emptying of the bladder and at the same time impermeable to fluid and able to cope with the varying pH, osmolality, and toxicity, for example, high ammonium concentration. It is composed of different layers of cells with the umbrella or facet cells lining the lumen are multinuclear, large cells with uroplakin facing the urine. Uroplakins are proteins contributing to the impermeability of the epithelium but can also act as a receptor for type 1 fimbriae on the uropathogenic E. coli [27].
The important step in the pathogenesis of UTIs is the adherence of uropathogens to the bladder mucosa. Therefore, adhesins (fimbriae) are important virulence factors. Although virulence factors have been distinguished best in E. coli (the most common uropathogen), many same principles may be applicable to other Gram-negative uropathogens, for example, Klebsiellae. Type 1 fimbriae mediate the adherence of glycoprotein receptors (uroplakins) on the uroepithelial cells to E. coli, whereas P fimbriae bind to glycolipid receptors in the kidney [25].
5.3. Immune dysfunction
It is observed that hyperglycemic environment alters immune function in patients with diabetes. Several aspects of immunity may be affected, including polymorphonuclear leukocyte function and adhesion, phagocytosis, and chemotaxis. This may play a part in the pathogenesis of urinary tract infections in patients with diabetes. Lower urinary concentrations of interleukin-8 and interleukin-6 in women suffering from diabetes have been shown to correlate with a lower urinary WBCs count that may contribute to the increased incidence of UTIs in this patient group [28].
If UPEC comes in contact with the epithelium, within minutes, the antimicrobial peptide cathelicidin is secreted and acts on the bacteria. Within hours, cytokines and chemokines are produced and their signaling will start to fix professional immune cells to the site of infection. The bacteria on the other hand will try to circumvent the immune defense in different ways. One is to enter the cell cytoplasm and form intracellular bacterial communities (IBCs) in order to “hide” from the immune response [29]; another is to down regulate the immune response with different modes of signaling. Depending on the number of bacteria, the host status, and the virulence factors they carry, the bacteria will either survive in the urinary tract or be eliminated and washed out with the urine [29].
If this first line of defense against pathogens entering the urinary tract fails, an inflammatory response is initiated. Attachment to the bladder uroepithelial cells by bacterial fimbriae allows for close contact between host and pathogen. Trans-membrane signaling through TLRs leads to the production of inflammatory mediators such as chemokines with subsequent recruitment of professional immune cells to the infectious focus. Chemokine IL-8 is required for neutrophil recruitment and activation in the urinary tract [30].
When the inflammatory response subsides, bacteria may still be left in the bladder epithelium. Bacteria that form IBCs can escape the different steps in host defense and treatment with antibiotics will be less efficient because of poor antibiotic penetration into the IBCs. From the IBC, bacteria can be expelled from the cells by a TLR4 mediated mechanism or in mature IBCs, and bacteria form filamentous structures and then separate from the cell to colonize adjacent cells. The cells may also be exfoliated, allowing the underlying immature cells to be exposed to further UPEC invasion. Here, they can turn into quiescent intracellular reservoirs (QIRs) for weeks, only to re-emerge to cause recurrent infections. Pyelonephritis may develop if the bacteria ascend further in the urinary tract. In the kidney, bacteria may cause damage of tissue and reach the blood circulation, causing septicemia, commonly called urosepsis. This increases the mortality from 0.3% in pyelonephritis to 7.5–30% in urosepsis [31].
6. Classification of urinary tract infection
UTIs are classified based on laboratory data, clinical symptoms, and microbiological findings. Practically, UTIs have been divided into uncomplicated and complicated UTIs and sepsis. The present guidelines give an outline of a tentative improved system of classification of UTI based on various factors as follows: (Guidelines on Urological Infections by European Association of Urology)
Classification based on grade of severity of infections and symptoms
Classification based on underlying risk factors
Classification based on anatomical level of infection
Classification based on microbiological findings
Classification based on complications
7. Diagnosis of urinary tract infection in diabetics
Upper and lower UTI can be suspected in diabetic patients with most common symptoms. Symptoms vary in upper and lower UTI. Table 1 highlights the symptomatic difference between upper and lower UTI.
Lower UTI
Upper UTI
Frequency
Urgency
Dysuria
Suprapubic pain
Costovertebral angle pain/tenderness fever and chills, with or without lower urinary tract symptoms
Table 1.
Symptomatic difference between upper and lower UTI.
Diagnosis of urinary tract infection can be done by following methods.
Examination of midstream urine specimen: After the symptomatic identification, a midstream urine sample should be examined for the presence of WBCs, as pyuria is present in almost all cases of UTI.
Pyuria detection: Pyuria can be detected either by microscopic examination (defined as >10 leukocytes/mm3) or by dipstick leukocyte esterase test (sensitivity of 75–96% and specificity of 94–98%).
Colonization: An absence of pyuria on microscopic assessment can suggest colonization, instead of infection, when there is bacteriuria [32].
Microscopic examination: Allows for visualizing bacteria in urine.
Dipstick: Tests for the presence of urinary nitrite.
Positive test: Indicates the presence of bacteria in urine.
Negative test: is the product of low count bacteriuria or bacterial species that lack the ability to reduce nitrate to nitrite (mostly Gram-positive bacteria).
Urine culture: Should be done in all cases of suspected UTI in diabetic patients, prior to initiation of treatment (preferred method of obtaining a urine sample for culture is from voided, clean-catch, and midstream urine) [33].
7.1. Diagnosis of UTI in women patients
All women with recurrent UTI should undergo a physical examination to evaluate urogenital anatomy and vaginal tissues estrogenization. Postvoid residual urine volume also should be measured. Diabetes screening is indicated in patients with other risk factors like family history and obesity. Most women do not need extensive urologic investigations. However, women who suffer infection with organisms which is not common causes of UTI, such as Proteus, Klebsiella, Enterobacter, and Pseudomonas, may have structural abnormalities or renal calculi. They would benefit from imaging studies of the upper urinary tract and cystoscopy. Women who have persistent hematuria after recovery of their infection also require a complete urologic workup. Although empirical therapy based on symptoms is generally accurate and cost-effective, women who are thought to be in the early stages of a problem with recurrent UTI should have documented cultures. Urine culture serves as the gold standard for diagnostic accuracy. The standard definition of a UTI on culture is >100,000 colony forming units per HPF. This value has excellent specificity but a sensitivity of only 50% [34].
8. Complications of urinary tract infection in diabetics
Emphysematous pyelonephritis (EPN) is a severe and necrotizing form of multifocal bacterial nephritis along with gas formation within parenchyma of the kidney. So far, more than 200 cases have been reported in literature. Underlying poorly controlled diabetes mellitus is present in up to 90% of affected patients [28].
The commonest offending organisms are Klebsiella and Escherichia coli followed by Proteus. The clinical manifestations are nonspecific and not different from the classic triad of upper UTI (i.e., fever, flank pain and pyuria); due to this, the diagnosis of EPN is often delayed. Disseminated intravascular coagulopathy, acute respiratory distress syndrome, disturbance of consciousness, acute renal failure, and shock can reveal some severe forms. Diabetic ketoacidosis is a very uncommon presentation, and only few cases have been reported so far.
EPN needs a radiological diagnosis. Conventional radiography may indicate gas bubbles overlying the renal fossa. Ultrasonography (US) characteristically shows an enlarged kidney that contains high amplitude echoes within the renal parenchyma. Computed tomography (CT) is the imaging procedure of choice, which confirms the presence and extent of parenchymal gas.
9. Pathogens of UTI in diabetes
A descriptive, cross sectional study was conducted on UTI and antibiotic sensitivity pattern among diabetic patients in National Academy of Medical Sciences (NAMS), Mahabouddha, Kathmandu, Nepal. According to this study, E. coli is the most common organism followed by Klebsiella, Proteus, and Pseudomonas. Most of the urinary isolates were sensitive to Ceftriaxone, Ciprofloxacin, and Cotrimoxazole, whereas resistance was high for ampicillin [35].
A study was conducted to find out the prevalence of UTI in diabetic patients. A total of 1470 diabetic patients (847 women and 623 men) were included in the study, admitted to the Diabetes Clinic of the Emergency Clinical County Hospital Timişoara between January and December 2012. According to this study, 10.7% in overall population had positive urine cultures. In this population, almost 78% of patients were having asymptomatic bacteriuria. The most frequent bacteria involved in UTI are Escherichia coli (68.9%) [9].
About 10.5% of type 2 and 12.8% of type 1 diabetic patients had UTI. There is no significant difference between type 1 and type 2 diabetes (p = 0.45); 4.5% of men and 15.3% of women developed UTI, an extremely significant difference (p < 0.0001)
Chiţă et al. concluded that urinary tract infections are more prevalent in diabetic patients. Because of the high proportion of asymptomatic forms among diabetic patients, the urine culture should be done in all hospitalized patients with diabetes.
The pathogens involved in causing urinary tract infection in diabetic patients and their frequency are mentioned in Table 2.
Gram-negative microorganisms
Frequency (%)
Gram-positive microorganisms
Frequency (%)
Escherichia coli
56.75
Alpha Streptococci
33.33
Klebsiella pneumonia
21.62
Staphylococcus aureus
66.66
Pseudomonas aeruginosa
9.54
S. epidermidis
0
Enterobacter aerogenes
4.05
—
—
Proteus mirabilis
4.05
—
—
Citrobacter freundii
4.05
—
—
Table 2.
Pathogens of UTI in diabetes.
10. Management of urinary tract infections in diabetics
Generally, treatment of UTI is similar in both diabetic patients and nondiabetic patients [5]; however, the choice of antibiotics in UTI patients with diabetes is one of the important considerations in the therapeutic management. Possible drug interactions between antimicrobials and antidiabetics or certain antibiotics may lead to impaired glucose homeostasis.
UTI treatment in diabetes patients depends on various factors including [5];
Presence of symptoms
Presence of infection in the bladder (lower UTI) or also involves the kidney (upper UTI)
Presence of urologic abnormalities
Severity of systemic symptoms
Occur with metabolic alterations and renal function
Moreover, UTI treatment varies based on patient’s age, sex, infecting agent, underlying disease, and whether there is lower or upper urinary tract involvement. Several clinical trials revealed that increasing trends of resistance to many antimicrobials with the increasing trend of antibiotic resistance in E. coli, with limited therapeutic options, the management of urinary tract infections is likely to become complicated.
10.1. Treatment recommendations for UTI in diabetes according to Infectious Diseases Society of America (IDSA)
10.1.1. Acute cystitis management in patients with type II diabetes
Acute cystitis treatment should be tailored according to culture results, if obtained. Apart from proper glucose control, one of the following UTI treatments is mandatory for acute cystitis management [36]. First line treatment management: Nitrofurantoin 100 mg three times daily for 5 days or fosfomycin trometamol 3 g single dose, or trimethoprim-sulfamethoxazole 960 mg twice daily for 3 days (can be used empirically only if resistance prevalence is known to be less than 20% and medication was not used in previous 3 months). Second line management: Quinolones and β-lactams.
10.1.2. Pyelonephritis management in patients with type II diabetes
Hospitalization should be done for the patients with severe symptoms for initial intravenous antibiotic therapy [5, 36]. Empiric antibiotics treatment: broad-spectrum cephalosporins, aminoglycosides, fluoroquinolones, piperacillin-tazobactam, or carbapenems should be started [37]. Severe sepsis presenting patients or those known to harbor-resistant uropathogens or the patients who have received multiple antibiotic courses should receive broad-spectrum coverage, guided by current urinary culture report. Treatment should be tailored when culture reports are available.
11. Antimicrobial agents
There are several types of antimicrobial agents such as antibiotics, antifungals, antivirals, antimalarials, and anthelmintics. Likewise, there are several types of microorganisms such as bacteria, fungi, viruses, and parasites. Microorganisms are responsible for various infectious diseases and sometimes leading to death. Antimicrobial agents play an essential role in decreasing morbidity and mortality associated with infections. Antimicrobial agents increased the life expectancy and quality of life. Different antimicrobial agents and their mechanism of action are mentioned in Table 3.
Different antimicrobial agents and its mechanism of action.
11.1. Benefits of antimicrobial agents
Prevent and treat infection
Increased the expected life spans of human being
Prevent or treat infection after surgery (C section, organ transplants, joint replacements, etc.)
Prevent or treat infection at the time of chemotherapy treatments
Antimicrobial drugs decrease the morbidity and mortality caused by food-borne, water-borne, and other poverty-related infections
12. Antimicrobial resistance
Resistance to antibiotics and other types of antimicrobial agents is growing and represents the single greatest challenge in the treatment of infectious diseases today. According to WHO, “AMR occurs when microorganisms change when they are exposed to antibiotic and antimicrobial drugs.” Due to anti microbial resistance, antimicrobial agents turning ineffective and infections persist in the body, increasing the risk of spread to others. AMR affects the effective prevention, and treatment of infections caused by bacteria, parasites, viruses, and fungi. WHO says that AMR is a growing and alarming threat to global public health that requires lot of action from the government. Moreover, people should get a lot of awareness message regarding antimicrobial resistance. An antimicrobial resistance developing microorganisms are sometimes called as “superbugs” [38].
As per WHO cost analysis data, health care cost of resistant infections is higher than nonresistant infections because of
Longer duration of illness
Additional tests
Use of more expensive drugs
Global WHO statistics says that a total of 480,000 people develop multidrug resistant TB each year, and drug resistance is starting complication in treatment of HIV and malaria as well.
12.1. Emergence of drug-resistant bacteria
Emergence of penicillinase-producing Staphylococcus aureus and emergence and spread of multidrug-resistant S. aureus in the early 1960s, emergence of MRSA in 1961, emergence of PISP in 1967, emergence of penicillinase-producing H. influenzae in 1974, emergence of PRSP in 1977, emergence of BLNAR H. influenzae in 1980, emergence of ESBL-producing Gram-negative bacilli in 1983, emergence of VRE in 1986, increased infections with MRSA, PRSP, BLNAR, etc. and increase of resistant gonococci in 1990s, increase of MDRP, and increase of quinolone-resistant E. coli in 2000s are the emergence of drug resistance bacteria.
Major reasons for increasing antimicrobial resistance:
Ineffective infection-control practices
Noncompliance with infection-control practices
Using sub-optimal dose of antibiotics for prophylaxis and treatment of infection
Multiple comorbidities in hospitalized patients
Prolonged hospitalization
Increased number and duration of intensive care unit stays
Colonized patients transfer from hospital to hospital
Grouping of colonized patients in long-term-care facilities
Major mechanisms for acquired antimicrobial resistance:
Enzyme that degrades the antimicrobial agent
Enzyme that alters the antimicrobial agent
Mutation in the antimicrobial agent’s target which reduces the antimicrobial agent binding.
Posttranslational or posttranscriptional modification of the antimicrobial agent’s target, which reduces binding of the antimicrobial agent
Reduced uptake of the antimicrobial agent
Active efflux of the antimicrobial agent
Antimicrobial agent target overproduction
13. Conclusion
Urinary tract infections are more common in the diabetic patients. Diabetic patients are severely affected with urinary tract infection. Treatment of UTI without proper diagnosis may lead to antimicrobial drug resistance. Treatment with antimicrobial agents should be started on the basis of culture reports. Only bacteriuria with symptoms of UTI should be treated with antibiotics to avoid the spread of drug resistant pathogens in the society. This practice can reduce the morbidity and mortality in diabetic patients suffering from urinary tract infection. The multidrug resistant pathogens are a challenge to society.
\n',keywords:"diabetes mellitus, urinary tract infection, Gram-negative bacilli, antibiotic, antimicrobial resistance",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/64419.pdf",chapterXML:"https://mts.intechopen.com/source/xml/64419.xml",downloadPdfUrl:"/chapter/pdf-download/64419",previewPdfUrl:"/chapter/pdf-preview/64419",totalDownloads:2518,totalViews:2121,totalCrossrefCites:2,totalDimensionsCites:6,totalAltmetricsMentions:7,impactScore:4,impactScorePercentile:90,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"February 19th 2018",dateReviewed:"June 17th 2018",datePrePublished:"November 16th 2018",datePublished:"February 13th 2019",dateFinished:"November 16th 2018",readingETA:"0",abstract:"Diabetes is a metabolic disease with increase blood sugar level. A large population of world is affected by diabetes. The patients suffering from diabetes have many other complications like cardiovascular disease, kidney disease, retinopathy, diabetic foot, diabetic neuropathy, urinary tract infection, etc. The patients with diabetes are more prone to get urinary tract infection due to frequent urination and high blood sugar level. The high sugar level gives favorable growth environment to the pathogens. Early diagnosis and proper medication are necessary for management of urinary tract infection in diabetic patients. The diagnosis of urinary tract infection is dependent on urine culture reports. The treatment should preferably be started after antimicrobial susceptibility reports. The misuse or overuse of antibiotics may lead to antimicrobial resistance. The antimicrobial resistance is another challenge in management of urinary tract infection.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/64419",risUrl:"/chapter/ris/64419",book:{id:"7452",slug:"microbiology-of-urinary-tract-infections-microbial-agents-and-predisposing-factors"},signatures:"Ajay Kumar Prajapati",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Diabetes",level:"1"},{id:"sec_3",title:"3. Types of diabetes",level:"1"},{id:"sec_4",title:"4. Urinary tract infection in diabetics",level:"1"},{id:"sec_5",title:"5. Pathogenesis of UTI in diabetics",level:"1"},{id:"sec_5_2",title:"5.1. Presence of glycosuria",level:"2"},{id:"sec_6_2",title:"5.2. Increased adherence to uroepithelial cells",level:"2"},{id:"sec_7_2",title:"5.3. Immune dysfunction",level:"2"},{id:"sec_9",title:"6. Classification of urinary tract infection",level:"1"},{id:"sec_10",title:"7. Diagnosis of urinary tract infection in diabetics",level:"1"},{id:"sec_10_2",title:"7.1. Diagnosis of UTI in women patients",level:"2"},{id:"sec_12",title:"8. Complications of urinary tract infection in diabetics",level:"1"},{id:"sec_13",title:"9. Pathogens of UTI in diabetes",level:"1"},{id:"sec_14",title:"10. Management of urinary tract infections in diabetics",level:"1"},{id:"sec_14_2",title:"10.1. Treatment recommendations for UTI in diabetes according to Infectious Diseases Society of America (IDSA)",level:"2"},{id:"sec_14_3",title:"10.1.1. Acute cystitis management in patients with type II diabetes",level:"3"},{id:"sec_15_3",title:"10.1.2. Pyelonephritis management in patients with type II diabetes",level:"3"},{id:"sec_18",title:"11. Antimicrobial agents",level:"1"},{id:"sec_18_2",title:"11.1. Benefits of antimicrobial agents",level:"2"},{id:"sec_20",title:"12. Antimicrobial resistance",level:"1"},{id:"sec_20_2",title:"12.1. Emergence of drug-resistant bacteria",level:"2"},{id:"sec_22",title:"13. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Kofteridis DP, Papadimitraki E, Mantadakis E, et al. Effect of diabetes mellitus on the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis. Journal of the American Geriatrics Society. 2009;57(11):2125-2128'},{id:"B2",body:'American Diabetes Association. Diagnosis and classification of diabetes Mellitus. Diabetes Care. 2005;28(Suppl 1):537-542'},{id:"B3",body:'Bastaki S. Review diabetes mellitus and its treatment. International Journal of Diabetes and Metabolism. 2005;13:111-134'},{id:"B4",body:'Ocvirk S, Kistler M, Khan S, Talukder SH, Hauner H. Traditional medicinal plants used for the treatment of diabetes in rural and urban areas of Dhaka: An ethnobotanical survey. Journal of Ethnobiology and Ethnomedicine. 2013;9:43-50'},{id:"B5",body:'Fünfstück R, Nicolle LE, Hanefeld M, Naber KG. Urinary tract infection in patients with diabetes mellitus. Clinical Nephrology. 2012;77(1):40-48'},{id:"B6",body:'Wang MC, Tseng CC, Wu AB, et al. Bacterial characteristics and glycemic control in diabetic patients with Escherichia coli urinary tract infection. Journal of Microbiology, Immunology, and Infection. 2013;46(1):24-29'},{id:"B7",body:'Truzzi JC, Almeida FM, Nunes EC, Sadi MV. Residual urinary volume and urinary tract infection: When are they linked? The Journal of Urology. 2008;180(1):182-185'},{id:"B8",body:'Hosking DJ, Bennett T, Hampton JR. Diabetic autonomic neuropathy. Diabetes. 1978;27(10):1043-1055'},{id:"B9",body:'Chita T, Licker M, Sima A, Vlad A, Timar B, Sabo P, et al. Prevalence of urinary tract infections in diabetic patients. Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2013;20:99-105'},{id:"B10",body:'Saravanan M, Sudha R. Survey on urinary tract infection associated with diabetes mellitus. 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Pathogenesis and management of bacterial urinary tract infections in adult patients with diabetes mellitus. International Journal of Antimicrobial Agents. 2003;22(Suppl 2):S35-S43'},{id:"B16",body:'Lye WC, Chan RKT, Lee EJC, et al. Urinary tract infections in patients with diabetes mellitus. The Journal of Infection. 1992;24:169-174'},{id:"B17",body:'Geerlings SE, Brouwer EC, Gaastra W, et al. Effect of glucose and pH on uropathogenic and nonuropathogenic Escherichia coli: Studies with urine from diabetic and nondiabetic individuals. Journal of Medical Microbiology. 1999;48(6):535-539'},{id:"B18",body:'Alteri CJ, Smith SN, Mobley HL. Fitness of Escherichia coli during urinary tract infection requires gluconeogenesis and the TCA cycle. PLoS Pathogens. 2009;5(5):e1000448'},{id:"B19",body:'Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. 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Intracellular lifestyles and immune evasion strategies of uropathogenic Escherichia coli. Annual Review of Microbiology. 2010;64:203-221'},{id:"B30",body:'Agace WW, Hedges SR, Ceska M, et al. Interleukin-8 and the neutrophil response to mucosal gram-negative infection. The Journal of Clinical Investigation. 1993;92(2):780-785'},{id:"B31",body:'Mysorekar IU, Hultgren SJ. Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(38):14170-14175'},{id:"B32",body:'Little P, Turner S, Rumsby K, et al. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technology Assessment. 2009;13(19):iii-iv. ix–xi, 1-73'},{id:"B33",body:'Bennett JE, Doli R, Blaser, Mandell MJ. Douglas, and Bennetts Principles and Practice of Infectious Diseases. 8th ed. Elsevier Inc; 2015'},{id:"B34",body:'Guido et al. The diagnosis of urinary tract infection: A systematic review. Deutsches Ärzteblatt International. 2010;107(21):361-367'},{id:"B35",body:'Simkhada R. Urinary tract infection and antibiotic sensitivity pattern among diabetics. Nepal Medical College Journal. 2013;15(1):1-4'},{id:"B36",body:'Gupta K, Hooton TM, Naber KG, et al. Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases. 2011;52(5):e103-e120'},{id:"B37",body:'Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. The Urologic Clinics of North America. 2008;35(1):1-12'},{id:"B38",body:'Antibiotic Resistance Questions & Answers. Get Smart: Know When Antibiotics Work. Centers for Disease Control and Prevention, USA. June 30, 2009. Retrieved March 20, 2013'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ajay Kumar Prajapati",address:"ajay_prajapati2000@yahoo.co.in",affiliation:'
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1. Introduction
The use of biomaterials in the reconstruction of injured body parts and skeletal healing is unavoidable. Diverse biomaterials including ceramics, metals, polymers, hydrogels, and composites are explored and have achieved clinical success as well [1, 2, 3]. For bone restoration applications ceramic biomaterials are well recognized by biomaterial engineers and medical experts due to their biocompatibility and osteoconductivity. Each bioceramic has its unique properties, and they can be divided into three categories based on the properties: [1] bioactive ceramics: capable of establishing chemical interaction with the cell surface, [2] bio-inert ceramics: fully unreactive to the living ecosystem, [3] resorbable bioceramics: undergoes in vivo deficiency for phagocytosis or dissolution of the biomaterials in human body fluids [4]. The standard bioactive ceramics used for bone-regeneration applications are bio-glasses and calcium phosphate-based resources, such as beta-tricalcium phosphate, hydroxyapatite, and biphasic calcium phosphate (mixture of beta-tricalcium phosphate and hydroxyapatite). However, alumina and zirconia oxide are the well-established bio-inert ceramics used in classic bone-regeneration applications [5]. Each bioceramics are widely used in the various human parts restoration applications based on the needs and capabilities. Excellent mechanical stability and biocompatibility brand zirconia as a potential dental restoration and bone scaffold material for load-bearing applications [6]. Hence, rigorous efforts were concentrated on zirconia-based ceramics in recent times by medical and research experts for dental and biomedical applications.
1.1 Overview of zirconia
Zirconia is a polycrystalline dioxide ceramic of the transition metal zirconium [3, 7]. It was originally documented in 1789 by Martin Heinrich Klaproth, a German chemist [8]. Zirconia exists in three distinct crystal structures depending on the pressure and temperature: monoclinic, tetragonal, and cubic structures [9]. The monoclinic crystal structure is more constant from room temperature to 1170°C, but it has inferior mechanical properties compared to the other two structures [10]. It is commonly accepted that the monoclinic structure will transform into a tetragonal structure during thermal treatment between 1170°C and 2370°C. This change in crystal structure is accompanied by measurable volume reductions (4–5%) during the cooling period [8]. If the temperature is increased further, the tetragonal structure shrinks to form a cubic structure (between 2370°C and 2680°C, the melting point). During cooling, a noticeable volume expansion of 3–4% was observed, which is attributable to the reversible transformation into the monoclinic crystal structure [9]. During phase transformation, internal stress is induced in the zirconia lattice, which results in crack propagation. To suppress the aforementioned behavior, several metallic oxides or dopants (stabilizing agents such as Y2O3, MgO, CaO, and CeO) are added to stabilize the zirconia structure, and the resultant type of zirconia is known as partially stabilized zirconia (PSZ) [11].
The key features of PSZ are their ability to enhance the transformation toughening mechanism, which inhibits/shields the further propagation of cracks. Therefore, PSZ is considered suitable for biomedical applications in orthopedics and dentistry due to its unique toughening behavior. In the late 1970s, zirconia was widely used as an effective substitute material for metals and alumina in biomedical and dental applications. This was due to its long-lasting mechanical behaviors, such as good flexural strength and fracture resistance, admirable biocompatibility, chemical permanency, corrosion resistance, and esthetics [12, 13]. Nevertheless, the aging process of zirconia ceramic is stimulated by low-temperature degradation, which has unfavorable impacts on the mechanical strength of prostheses and subsequent growth of external flaws. The presence of microcracks may compromise the performance in the long term in biological fluids [14].
To date, zirconia-based materials have been used in numerous areas in the engineering (energy and aerospace), medicine (orthopedics), and dental (crowns and implants) fields [15]. Common categories of zirconia-based materials existing on the market for biomedical applications are yttrium tetragonal zirconia polycrystal (Y-TZP), glass-infiltrated zirconia-toughened alumina (ZTA), and magnesia partially stabilized zirconia (Mg-PSZ). The properties of these zirconia-based bioceramics are listed in Table 1.
In general, zirconia-based ceramics are manufactured using conventional fabrication techniques, such as injection molding [17], hot and cold isostatic pressing, and slip casting [18]. Digital techniques such as computer-aided design (CAD) and computer-aided manufacturing (CAM) are extensively used to fabricate dental restorations [7, 19], as well as in subtractive manufacturing techniques, such as machining and milling. However, these techniques have limitations such as material wastage, difficulties in producing complex structures, being time consuming, and wearing of milling and cutting tools. Recently, additive manufacturing (AM) techniques have been increasingly used for the fabrication of high-potential complex ceramic parts with high precision and at reduced cost [20, 21]. Developments in AM technology for the fabrication of zirconia-based ceramic parts and their applications are discussed in the following section.
1.2 Additive manufacturing techniques
AM is one of the most widely used techniques in recent times, and it is capable of building three-dimensional (3D) complex geometric structures with high dimensional precision and within a short manufacturing time. 3D objects with high levels of complexity and structural architectures are fabricated by stacking up the materials layerwise using simulated design files [22, 23]. AM is also known as 3D printing, solid free-form fabrication, and rapid prototyping. The materials used for AM processes are in the form of powders, liquids, or solids. According to the ISO/ASTM 17296 standard, AM technology is mainly characterized into two types based on the degree of consolidation [24].
1.2.1 Single-step process or direct process
As the name suggests, the combined bulk product is manufactured with a basic/specified geometric shape in a single operation by melting and solidification or multi-pass welding (such as powder bed fusion, selective laser melting (SLM), or directed energy deposition), which is mostly used in metal AM.
1.2.2 Multistep or indirect process
It produces the products in multiple steps. First, the green body parts are constructed with the basic geometric shape by binding the powder particles with help of a polymer or binder. Subsequent steps include shape modification/densification, consolidation of the material, or modification of the material properties (such as binder jetting (BJ) and material extrusion). AM ceramics parts are typically formed using multistep progression [25].
For biomedical and dental applications, the 3D printing process principally comprises the following steps (precisely for clinical applications): 1. procurement of 3D models, 2. designing (CAD), 3. slicing, 4. 3D printing, and 5. postprocessing. Briefly, the AM process starts with the sorting of precise medical records (images) of the patients, which are obtained using computed tomography or magnetic resonance imaging. The procured data conforming to digital imaging and communications in medicine standards are transformed into digital models using materialise interactive medical image control system (MIMICS) or 3D DOCTOR software and formed into design files using 3D CAD software. The CAD file is converted to a standard tessellation language (.STL) file, and it is practically sliced to print patterns as per the specific needs of the implant. To acquire the desired print pattern of the products, numerous processing constraints such as printing speed, alignment, printing temperature, layer height, infill, laser condition, and environmental aspects are verified, based on experience or a literature review. The sliced file can be imported into the AM machine for printing/stacking the material in a layer, forming the 3D implant. Finally, the printed parts are exposed to washing, removal of sacrificial layer/support, and heat treatment [25, 26]. The detailed scheme of additive manufacturing process is displayed in Figure 1.
Figure 1.
Illustration of additive manufacturing process.
The most common AM technologies for the construction of high-strength ceramics are selective laser sintering/melting (SLS/SLM), stereolithography (SLA), digital light processing (DLP), binder jetting (BJ), fused deposition modeling (FDM), and direct ink writing (DIW) [27, 28]. Each AM technology has great commercial potential as well as limitations [29]. Likewise, additively manufactured zirconia-based ceramics have inferior mechanical properties due to the persistent porosity and flaw-sensitive properties of zirconia ceramics. Thus, acquiring mechanical properties equivalent to those of ceramics fabricated with more conventional approaches is a big challenge for ceramic AM [30]. However, the technology is still at an early stage, compared with conventional ceramic processing techniques [29]. It is widely recognized that ceramic materials possess a high melting point, high sinterability, and high vulnerability to thermal shock. Therefore, it is challenging to achieve fully consolidated parts, without shortcomings, using AM-based techniques that directly produce sintered objects [25]. To overcome these shortcomings, each AM technology adapts scientific strategies to construct zirconia-based ceramics with high accuracy and quality. In the following section, the formulation strategies of each AM technology are discussed. Figure 2, demonstrate the AM technologies used for the fabrication of zirconia parts.
Figure 2.
The schematic illustration of different types of AM technologies used for the fabrication of 3D zirconia-based ceramics.
2. Formulation and general properties of zirconia directed to biomedical applications
2.1 Powder bed method
2.1.1 Selective laser sintering/melting (SLS/SLM)
SLS technology uses a high-powered laser beam to sinter/fire the ceramics at an elevated temperature. The laser is aimed at specific areas of the aggregate powdered particles using the distribution to create solid objects [31, 32, 33]. The SLM is principally similar to SLS; however, SLM completely melts and fuses the powder particles using a high-powered laser beam to form a solid object [34, 35]. SLS/SLM is an AM technique that uses a laser and is based on the powder bed method that produces 3D solid structures either by sintering or melting the powder materials layerwise following an architecture based on CAD data. (Obtaining high-strength and high-density parts with a laser without debinding/sintering processes can facilitate effective and rapid fabrication, enabling the mass production of ceramic parts (direct AM process) [36, 37].
However, zirconia ceramic is difficult to handle with SLS/SLM, as it has a higher melting point than other bioceramics. In addition, reaching full densification and realizing crack-free final products made of ceramics-based materials using this process are still challenging. Therefore, several studies are investigating the effect of powder properties and processing parameters [21, 35, 38]. Researchers describe the effectiveness of pre-heating the powdered bed, which could improve the mechanical properties of the final ceramic object by reducing the thermal stress, which alleviates crack formation during printing [39, 40]. Most of the zirconia particles use 3–8 mol% yttria-stabilized zirconia (YSZ) to preserve the desired mechanical properties of a tetragonal phase at room temperature. Alternative approaches were also found to be effective in improving the mechanical properties of the zirconia. For example, composites comprising zirconia and alumina are also found to retain the tetragonal phase [40, 41, 42]. To improve the mechanical properties of the final zirconia part and prevent cracking, an indirect method in SLS/SLM has been developed and documented [42, 43, 44]. Specifically, ceramic powder particles are mixed/coated with a sacrificial polymer binder (which has a lower melting point than the ceramic) and the laser is targeted towards the powder, which melts and fuses the ceramic particles. The fused ceramic particles are then subjected to postprocessing (debinding and sintering) to attain the dense zirconia ceramic scaffolds [42]. The summary of zirconia-based ceramics printing configurations used in SLS/SLM methods is presented in Table 2.
Summary of zirconia-based configurations used in SLS/SLM methods [34].
2.1.2 Binder jetting (BJ)
BJ is also based on the powder bed fusion technique, where a binder (binding agent) is selectively deposited to link powder materials. In this technique, a thin layer of ceramic material in powder form is evenly spread over the building platform with the help of a roller [48]. A binding ink is then sprayed onto the ceramic powder particles using the jetting head. The result is the ceramic powders and binders adhering together to form a solid structure. This is repeated multiple times and the layers are printed on top of each other to form the preferred 3D scaffolds. During printing, green ceramic parts are reinforced by boundless powder particles [24]. The BJ process can eliminate the internal residual stresses that evolve during building [1]. Moreover, the postprocessing steps such as the removal of unbound powders and sintering are conducted to consolidate the dense ceramic parts. The effective production of numerous ceramics such as hydroxyapatite, tricalcium phosphate, ZTA, and Al2O3 structures with the required porosity using the BJ process have been reported in the literature for biomedical applications [49, 50]. However, obtaining the necessary shrinkage and density in the final product after sintering is still critical. Therefore, many researchers sought to address these issues by integrating nanoparticles into the liquid binder. Recently Huang et al. [32] studied the use of an inorganic colloidal binder (decomposable binder) as a binding agent for the construction of 3Y-ZrO2 ceramic structures using BJ technology. They selected zirconium basic carbonate as a precursor, and it was dispersed in the colloidal solvent to produce decomposable inorganic colloidal binder because it can be easily decomposed upon sintering and can form zirconia 3D parts with no residue [48]. It was established that the inorganic colloidal binder-based zirconia scaffolds exhibited superior surface quality and density compared to the conventional polymer binder. Conversely, Zhao et al. [32] ***attempted to print zirconia samples using a liquid binder containing zirconia nanoparticles (10 wt%). The density was increased by approximately 86.8%, whereas shrinkage was reduced by approximately 10.6% after sintering the printed parts [51].
2.2 Stereolithography
Among the AM technologies using zirconia, SLA technology is the most well-known and popular method. A photocurable resin comprising photopolymerizable monomers, a photoinitiator, and ceramic particles is molded into a slurry and selectively cured by ultraviolet (UV) radiation in sequential layers to build the 3D object with the desired shape [52]. The geometrical accuracy of the manufactured parts produced using SLA technology is dependent on the laser power, layer thickness, cure depth, and energy dose. The key steps in fabricating ceramic parts with complex geometries and high resolution using SLA are preparing a suitable photocurable ceramic suspension, building the ceramic part, and debinding and sintering [53]. One of the most important factors in this process is the properties of the ceramic suspension. Homogeneous dispersion of zirconia ceramic materials with raw resin is essential for establishing photocurable ceramic resins. The introduction of ceramic materials negatively impacts the properties of raw resin by increasing the viscosity and immobilizing the ceramic/resin suspension. To initiate a matrix around the ceramic materials during photopolymerization, a combination of monomers and oligomers is blended with the ceramic suspension as a binder [54]. It is essential to include a dispersant to prevent agglomerations and retain the resin stability. The dense ceramic parts fabrication is primarily dictated by the volume fraction of the ceramics. Increases in volume fraction improve the final properties of the product (porosity reduction, shrinkage reduction, strength improvement, crack/deformation suppression) [28]. Due to this unique characteristic, SLA-based printers are commercially available in different forms. Hence, design and materials engineers recommend altering the design and printing parameters to the finest quality using state-of-the-art techniques and materials. Many studies have been focused on advancing a suitable photocurable ceramic suspension for the fabrication of zirconia-based ceramic parts (Table 3).
Different formulations and viscosity characteristics for preparation of zirconia suspensions [53].
Acrylate-based monomer.
Acrylamide-based monomer.
Polyethylene glycol.
2.2.1 Oligomers and monomers
The oligomer (prepolymer) applied to the zirconia in AM methods has a chain structure comprising a medium molecular weight monomer. The oligomer regulates the physical properties of the resin. The reactivity between the monomer and the polymer with a low molecular weight number influences the properties of the cured film through molecular bonding triggered by polymerization. The classification is based on the molecular structure and includes polyester, epoxy, urethane, polyether, and polyacrylic. In general, it is difficult to use the oligomers directly for AM due to their high viscosity [60, 61].
A monomer is a reactive diluent added to reduce the viscosity of an oligomer. The polymerization can be categorized into two types, namely, a free radical reaction or a cationic reaction [60, 62]. Acrylates and methacrylate are the most used monomers from free radical reactions [62]. Photopolymerization can be stimulated through a free radical initiator, and when the monomer receives a free radical from the initiator, it transfers the free radical to another monomer to form a polymer. The cationic reactive monomers can induce photopolymerization via cationic initiators. Monomers, such as epoxides, vinyl ethers, propenyl ethers, siloxanes, cyclic acetals, and furfurals, are capable of polymerization under a cationic mechanism. Epoxide is the preferred monomer from the cationic reaction groups [63].
2.2.2 Photoinitiator
Monomers and oligomers cannot independently initiate photopolymerization. Therefore, photoinitiators are added to generate reactive species that can trigger the monomers and oligomers. When polymerization is initiated, the reaction proceeds through a chain reaction of double bonds and forms a three-dimensional cross-linked bond together with reactive monomers and oligomers [64, 65]. Free radical photoinitiators added to certain monomers, such as acrylates and methacrylates, absorb UV light to generate free radicals and incite a double bond reaction of the monomers [66]. Cationic initiators can readily react with the binding of certain monomers, such as vinyl ethers and epoxides, because the absorbed UV light produces acids to induce polymerization of the monomers [63].
2.2.3 Dispersant
Dispersants are copolymers with soluble polymer chains and “fixing groups” that impart affinity to the surface of inorganic pigments such as zirconia [53]. The main mechanism in nonaqueous systems with low polarity is steric stabilization. Polymer chains are attached to the pigment surface by adsorption and form a brush-like layer that prevents re-agglomeration due to osmotic and entropy effects. The polymer chains of the dispersant are adsorbed onto the pigment surface to form a layer that prevents re-agglomeration. An effective layer typically ranges from 5 nm to 20 nm, with a particle diameter in the range of 0.05–1 μm. Because the dispersant effects vary with the monomer and oligomer composition, as well as the properties of the ceramic powder, care must be taken regarding the type and content of the dispersant.
2.3 Material extrusion
The compact ceramic raw material supplied to the extruder is difficult to use as an AM material because it has a high tendency of particle aggregation and, thus, increased resistance to flow [67]. Compatible ceramic powder and additives can guarantee permanency for storage and molding through homogeneous particle dispersion after mixing and, thus, facilitate the minimum pressure and viscosity for flow through the printing nozzle [68, 69].
Additionally, there is a need for good bonding and inhibition of separation between the deposited layers during printing [70, 71]. In addition, the included additives must be removed without defects during the post-treatment process [72, 73].
2.3.1 Wax/thermoplastic base
A study on the composition of multicomponent additives for a wax/thermoplastic base is suggested in Table 4. In addition to the main additives (such as polyethylene), other components such as wax dispersants and plasticizers are also included to provide strength, elasticity, flexibility, plasticity, and lower viscosity [20].
Overview of extrusion processes for zirconia ceramics.
2.3.2 Water base
In the case of a feedstock in which a large amount of polymer is used as a dispersion medium, defects may occur during debinding after manufacturing. To solve this problem, an aqueous ceramic raw material is used. This water-based ceramic raw material enables the accumulation of zirconia powder with high content and decreases defects during degreasing due to the low content of organic matter.
3. Biomedical application of AM zirconia
3.1 Dental applications
The use of zirconia ceramic as a restorative material in the form of dental protheses started in the early 1980s and gained considerable attention in the dental community, thereafter due to its unique properties (such as excellent esthetics including tooth-like color, high fracture toughness, flexural strength, corrosion resistance, and biocompatibility) [8]. Hence, it has become the best alternative for metal-based dental restorations. Zirconia ceramics have been used in dental applications in the form of dental crowns, dental implants, and fixed partial dentures since 1998 [19]. In general, zirconia restorations are fabricated using digital techniques, including subtractive manufacturing techniques such as CAD/CAM, which is the established method for producing fixed prosthetic restorations [79], where the milling machine is controlled by a computer numeric controlled system. The power-driven milling tools were used to mill/remove the material from a block (presintered or fully sintered ceramic block) to achieve the desired prosthesis background [80]. However, it has certain disadvantages during manufacturing, such as material wastage and wear of milling tools. In addition, its precision is limited, limiting object complexity, tooling equipment dimensions, material properties, among other problems [81]. AM incorporates recent advanced and evolving techniques in digital dentistry, which construct the three-dimensional component by layering the material. It is capable of making cost-effective customized dental prostheses with minimal material consumption and high precision [82]. However, research studies on the 3D printing of zirconia crowns and bridges for dental applications are limited. In addition, various issues such as poor geometrical accuracy, high porosity, and poor margins are unresolved. Recently, several research studies on 3D printing of zirconia ceramics using photopolymerization-based printing (SLA-based technologies) improved the effectiveness and accuracy, making the technique favorable.
3.1.1 Restorative applications
The goal of the dentist is to restore the lost tooth as naturally as possible. The most common material types used in the restorative field are metals and ceramics. However, ceramics possess significant advantages over metal/metal ceramics due to their natural appearance (tooth-like color), which satisfies the esthetic demands, making ceramics the material of choice [83, 84].
YSZ is the most widely used all-ceramic material in dental restorations due to its outstanding material properties [85]. It is used for load-bearing applications, such as dental crowns, bridges, veneers, and implant abutments. YSZ restorations have been used in clinical practice over the past two decades. It is used primarily as a core material for the fabrication of dental prosthesis frameworks. The chipping of ceramic veneers and fracture of the framework, when exposed to continuous masticatory load is often reported [86, 87]. For example, the thermal coefficients of the core material and outer veneer cap (porcelain/lithium disilicate) are different and subjected to different heat treatment temperatures that lead to catastrophic failure. Further, several other factors including surface treatment (airborne-particle abrasion/etching) of the framework and bond strength between the ceramics veneer and zirconia frameworks are consequential [9, 88].
The advancement in zirconia with full-contour monolithic zirconia restorations gained attention to address the aforementioned problems. The fabrication of crowns and bridges using monolithic zirconia is faster and cheaper compared to a manually constructed veneered prosthesis. In recent years, CAD/CAM technology (subtractive) has been used for the fabrication of all-ceramic prostheses and abutments. The very attractive flexural strength and toughness of 3 mol% YSZ make it a classic and suitable material for dental use. Despite the promising properties of zirconia, the optical properties (translucency) are poor, i.e., it is opaque. Therefore, the larger esthetic-related issues initiated the demands for monolithic restorations. Dental material researchers and manufacturers have found several ways to increase translucency characteristics. The light transmission can be improved by either reducing the concentration of aluminum oxide or increasing the concentration of yttrium oxide [15]. For instance, the molar concentration of the yttria is varied (3–5%) to improve the translucency of zirconia with optimal mechanical properties. However, when the concentration of yttria is increased, the material exhibits higher translucency (more esthetics) but also exhibits a reduction in mechanical properties because the structural change into cubic phase becomes dominant. Evidently, the cubic phase does not allow transformation in crystal structure and this leads to a reduction in crack resistance. The “gradient technology” has become the modern advancement in the area of translucent zirconium oxide. A material-specific gradient is introduced into the milling block along with the color gradient (highly chromatic at the cervical region and less chromatic at the incisal region). In particular, the high-strength raw material 3Y-TZP is combined with the highly translucent raw material 5Y-TZP to create a continuous, layer-free color and translucent gradient [89]. The development of AM technology has attracted much attention to the fabrication of zirconia-based restoration with a high potential of making customized dental prothesis with minimal waste (Figure 3).
Figure 3.
AM zirconia crowns via DLP technology [56].
In 2009, Ebert et al. [90] built a zirconia dental crown using the direct inkjet printing method. The printing ceramic suspension was loaded with 27 vol% of zirconia ceramics, with a relative density of 96.9%, flexural strength of 763 MPa, and a fracture toughness of 6.7 MPa m1/2. The printed and fired samples showed process-related defects, which were attributed to the clogging of the nozzles during printing that directly affected the mechanical properties. However, the authors demonstrated the potential to print 3D crowns using this technology. Likewise, Özkol et al. [91] attempted to print the zirconia bridge framework using a direct ink printing (DIP) method. The ceramic aqueous ink was prepared with 40 vol% solid content of 3Y-TZP. The printed components were dried and sintered at 1450°C. The relative density of the final product was >96%. Furthermore, finite element analysis was used to determine the stress distribution and the maximum tensile stress of the framework structure. The results of all different loading cases show hot spots on the bottom marginal area of the interdental connectors. The estimated maximum tensile stress values ranged between 250 and 350 MPa. The flexural strength was approximately 843 MPa (Table 5).
Lian et al. [57] reported that complex zirconia bridges were produced using the SLA technique with a high shape precision. They prepared a 40 vol% zirconia suspension and the laser scanning speed of 1200 mm/s was optimized for printing. The density and Vickers hardness of the sintered bridges was 98.58% and 1398 HV, respectively. Nevertheless, the flexural strength (200.14) was very low, and it was not good enough for actual dental applications, because of the internal defects formed during the printing process. The authors, therefore, suggested a study of the further optimization of the parameters of the SLA and sintering process. Additionally, in 2019 Wang et al. [94] conducted an in vitro experiment to investigate the surface trueness at different locations (external, intaglio, marginal, and occlusal) of 3D printed zirconia crowns constructed using SLA 3D printing technology.
The point-to-point difference between the scan data (3D printing) and corresponding CAD model data determines the trueness of the fabricated crown. The comparative color maps could demonstrate the accuracy and inaccuracy between the 3D printing and milling techniques. Meanwhile, Li et al. [95] examined the internal and marginal adaptation of 3D printed zirconia crowns and studied the physical and mechanical properties. The authors achieved a consistent flexural strength of 812 MPa and Weibull modulus of 7.44 by using 45 vol% zirconia suspensions. The mechanical strength is sufficient for dental crowns fabrication. While the cement spaces in occlusal (63.4), axial (134.08), and marginal (169.65) areas were not ideal for clinical applications, this can be attributed to light scattering and anisotropic sintering shrinkage.
However, in 2019 Jang et al. [56] investigated the microstructure and physical properties of zirconia products fabricated via DLP technology. The zirconia suspension was prepared using different volume fractions of the ceramic content from 48 vol% to 58 vol%. Cracks were observed on the zirconia specimens, and these cracks increased in number as the zirconia volume fraction decreased. The 3-point bending strength, relative density, and shrinkage of the printed samples were 674.74 MPa, 83.02%, and 23.81%, respectively. The maximum volume fraction possible for 3D printing was 58 vol%.
More recently in 2021, Zandinejad et al. [96] investigated the fracture resistance of AM zirconia crowns cemented to an implant-supported zirconia abutment. They also compared the AM zirconia crowns with milled zirconia, as well as lithium disilicate crowns. A universal testing machine at a crosshead speed of 2 mm/min was used to determine the fracture resistance, and it was verified that the fracture resistance of AM zirconia is equivalent to milled crowns. Nevertheless, intra-oral simulation research on the AM ceramic crowns should be conducted to authorize AM as a real-world technology for the construction of ceramic restorations in clinical dentistry.
3.1.2 Implant application
The popularity of zirconia-based implants is growing enormously as an alternative to alumina and metal-based endosseous implants [104]. Since the late 1980s, zirconia has been used to build surgical implants for the replacement of total hip prostheses in orthopedic surgery [105]. Zirconia-based ceramics have superior mechanical properties and corrosion resistance [106]. Besides, in vitro and in vivo,clinical studies of zirconia implants revealed excellent biocompatibility, osseointegration and a low affinity for bacterial plaque compared to standard metal implants (titanium implants) [107, 108, 109]. The utilization of AM technology is beneficial for the fabrication of zirconia-based ceramic dental implants as they can produce customized geometrics and complex structures. The technology can also improve bioactivity without any surface alterations, such as sandblasting, etching or coating [104]. Nevertheless, it is essential that the functional surface quality of zirconia-based implants fabricated from conventional techniques be enhanced to improve mechanical functions such as wear resistance and fatigue. Moreover, the surface treatments can improve bioactive functions, such as cell proliferation, adhesion, bonding strength, and bacterial decolonization [110].
For example, Osman et al. [111] fabricated 3D printed zirconia implants using DLP technology and evaluated the dimensional accuracy, surface topography, and flexural strength (Table 6). They showed that custom-designed 3D printed implants revealed satisfactory dimensional precision (root mean square error of 0.1 mm), and the flexural strength (943.2 MPa) is equivalent to that of conservative milled zirconia (800–1000 MPa). The roughness of the surface was found to be 1.59 μm and from the SEM analysis, it was observed that the presence of microporosities with interconnected pores (196 nm to 3.3 μm) and cracks were visible. These flaws were generated during the sintering process or improper dispersion of ceramic particles into the slurry. To enhance the potential microstructure quality of the printed implants, 3D printing parameters need to be optimized.
However, Nakai et al. [82] inspected the microstructure and flexural strength of zirconia-based ceramics formed using SLA (AM technology) and related to CAD/CAM technology (subtractive technology). In their study, the authors compared the commercially available zirconia-based ceramics products. They were two AM 3Y-TZP (LithaCon 3Y 230 and 3D Mix zirconia) products, and one AM ATZ (3DMix ATZ) product, with conventionally fabricated 3Y-TZP (LAVA plus). The experimental outcomes confirmed that the flexural strength and microstructure of AM zirconia are sufficient and close to that of conventionally (subtractive) manufactured zirconia. AM ATZ exhibited higher flexural strength (1108.8 MPa) than 3Y-TZP. Both 3Y-TZP and ATZ are suitable for dental implants. Moreover, variation in the AM process and the impact of building alignment can alter the mechanical properties of AM zirconia. To promote the practical reliability of AM zirconia implants, the relationship between the surface morphology and bioactivity of zirconia needs to be evaluated in a future study. Recently, Magnani et al. [116] presented the potential capability of DLP printing technology to fabricate the dental implants with a new high-performance ATZ composite material (Figure 4).
Figure 4.
Dental implant fabricated using DLP-based additive manufacturing technology. (a) ATZ dental implant-green body, (b) micrograph of the lattice structure [116].
3.2 Bone-regeneration applications
The clinical success of zirconia bioceramics in the human environment in the form of dental posts, teeth, and crowns in the dentistry field encouraged biomedical researchers to exploit the biological and mechanical properties of zirconia bioceramics for bone-regeneration applications. Accordingly, developing zirconia-based scaffolds with high precision and dimensional stability is vital to satisfy increasingly challenging requirements for bone-regeneration requests. At present, there is a lack of a simple commercial approach to construct 3D zirconia structures, however, the proposal of AM in 3D zirconia scaffold construction shows great potential. Biomedical engineers targeted AM-based technologies for the zirconia scaffold preparations (Table 7). Unlike conventional bioceramics, initial attempts to fabricate zirconia bioceramics were mainly concentrated on multi-pass extrusion techniques [44]. The multi-pass extrusion technique is a simple AM technique in which the ethylene-vinyl acetate polymers were blended with zirconia powders to execute extrusion (the extrusion is repeated to construct the scaffold with constant porous core structure). The extrusion proportion, pore-gradient rate, and microstructure are the critical parameters in controlling the final output of the zirconia scaffolds. More importantly, to increase the biocompatibility of zirconia binary mixtures (ZrO2/Al2O3), fabrication of binary scaffolds with alternating ZrO2 and Al2O3 layers with 3D-interconnected micropores are also demonstrated [136]. However, the multi-pass extrusion designs were not controlled using modern numerical methods. In subsequent years, computerized extrusion-based techniques like 3D Bioplotter and FDM were introduced to precisely design the 3D zirconia scaffolds. Zirconia-based scaffolds (β-Ca2SiO4/zirconia scaffolds) fabricated using the 3D-Bioplotter technique were verified to induce bone-regeneration properties in an actual biological atmosphere using a rat model [131]. In FDM, zirconia ceramics are generally blended with polymers such as polycaprolactone to execute a computerized melt mixing process, which can construct a regular grid scaffold [133]. More importantly, biopolymers embedded in zirconia-based scaffolds fabricated using FDM were found to provide additional mechanical support, as well as bioactivity for the zirconia ceramics (Figure 5). Compared to the pristine zirconia-based scaffolds (alginate/gelatine), biopolymer embedded zirconia ceramics were found to exhibit the extracellular matrix (ECM) of the bone tissue, which is essential to imitate the biological environment [74]. Subsequently, considerable research efforts were dedicated to formulating zirconia-based scaffolds using the direct ink writing (DIW) or robocasting method (extrusion-based AM-based technique). 3D zirconia scaffolds fabricated with controlled pore openings and thread dimensions using the DIW method were found to possess high porosity (61% and 75%). More importantly, hydroxyapatite/fluorapatite-based coatings on the DIW derived zirconia-based scaffolds were needed to enhance its bioactivity [135]. Photopolymerization-based AM techniques including DLP and SLS were also studied for the fabrication of zirconia-based scaffolds. Specifically, DLP technology was found to have high accuracy and faster processing ability than other AM-based techniques. The ultraviolet light is irradiated on the zirconia suspensions (prepared by optimizing the solid loading of the zirconia powders, organic monomer, potentiators, and dispersant) to articulate the final design. It is important to perform heat treatment in a high-temperature vacuum furnace to avoid internal cracks and imperfections in the heat-treated zirconia scaffolds [132]. Although SLS-based techniques were widely studied for calcium-based bioceramics, the use of SLS techniques to construct zirconia has been limited due to low zirconia concentration. Mostly, zirconia is blended in minimum volume fraction with other bioactive materials like calcium silicates to avoid the unwanted agglomeration-induced material degradation [124]. In addition, to replicate the nano-to-microscale configuration of the ECM of bone tissue, electrospinning of the zirconia-based scaffolds was experimented with. It is believed that the zirconia scaffolds subjected to electrospinning exhibited high endurance to the inbound load from the bone tissue when compared to conventional more fragile scaffolds [125].
Materials
Fabrication techniques
Composite/coating materials and infiltration/intermediate layer
AM zirconia for bone tissue regeneration applications.
Figure 5.
(a) Scaffold printing using FDM, (b) digital photograph of the printed zirconia scaffold, (d) microscopic images of zirconia scaffold, and (e) polymer embedded zirconia scaffold [74].
4. Outlook and prospective
Zirconia is a classic bioceramic, and its use in the dental and biomedical fields is inevitable. Hence, extensive research efforts have been dedicated to maximizing the potential of AM technologies to formulate the zirconia ceramics into a precise bone or tooth replacement, scaffolds, implants, and crowns. Though, zirconia scaffolds are directly involved in the human environment (in both dental and biomedical fields), the requirements of each field are evidently different. For instance, the zirconia scaffolds should have adequate porosity for bone-regeneration applications and patient-specific design, whereas, zirconia scaffolds for dental restoration and implants need not have a porous structure; instead, they should retain complex shapes with solid/hollow structures. Hence, the scaffold processing via AM also needs to be precise for each application. AM or 3D printing has revolutionized the designing of complex human hard tissues with an excellent surface finish, minimum material wastage, and high fabrication speed compared to conventional techniques. However, AM also suffers from some inherent limitations and challenges. The primary challenges include difficulties in raw material preparation, process control, and immature designs (Figure 6). Research advancements achieved by the metal and polymers-based scaffolds via AM-based techniques both in the laboratory and at clinical levels are far ahead when compared to the practically challenging zirconia-based ceramics due to their inherent challenging properties (brittleness, high melting point, and high density). Hence, it is essential to pinpoint the existing challenges in the research investments and activities that restrict the feasibility of AM-based technologies in fabricating zirconia-based ceramics at the laboratory, clinical, and industrial levels.
Figure 6.
Major challenges of AM zirconia-based ceramics.
4.1 Laboratory challenges
Although different types of AM technologies are available for formulating bioceramics, only a few techniques are effective in the fabrication of zirconia parts with minimal imperfections. Despite the large number of AM technologies suitable for processing ceramics, each technique has its individual advantages and limitations. The primary issue for printing starts from the raw material (feedstock/slurry) preparation itself. For example, in extrusion-based techniques, temperature, pressure, nozzle size, and computer-generated design files (scaffold models) can be fed easily to the computer to accomplish the anticipated requirements. However, poor printability, nozzle blockage, and poor flowability of the feedstock have been major bottlenecks (due to the high density and hardness of zirconia) in designing zirconia-based scaffolds for bone-regeneration applications.
Compared to FDM-based techniques, SLA-based techniques have been extensively explored for the fabrication of zirconia-based ceramics due to the excellent surface finish and precision produced by the technology. Commercial SLA printers are now available for zirconia-based ceramics. However, the uneven distribution and particle aggregation of zirconia particles in the slurry suspension upsetting the light scattering properties (cure depth, curing time, and the energy of the UV light source) is a challenging issue. As a result, geometrical overgrowth is unavoidable due to the high refractive index of the zirconia. (SLA-based techniques are mainly controlled by the light source, refractive index, volume fraction, and particle size.) The most common problem associated with SLA-based techniques for zirconia-based ceramics is the delamination among the layers, which invariably disturbs the physical and mechanical properties of the sintered zirconia parts.
SLS-based techniques, however, can produce scaffolds with high precision, but they are rarely explored for zirconia-based ceramics due to the expensive and complicated control parameters. In particular, the high melting point of zirconia requires pre-heating of the powder bed (>1000°C) to avoid cracks caused by the thermal stress induced by the high-power laser source. Nevertheless, SLS-based techniques have represented a single-step scaffolding process for formulating zirconia scaffolds with full density. The requirement and urgency of developing this technique further for zirconia-based scaffolds are debatable.
For all the above, the major disadvantages of AM-based techniques except direct SLS-based techniques are the low-volume fraction of the zirconia in the feedstock (<60%, in which the polymer occupies the remaining portion). After debinding of polymers, the printed scaffolds can retain only half of the parent zirconia properties, which invariably affects the expected properties of the final sintered zirconia-based scaffolds.
In general, the strength and life of ceramic materials are directly associated with the type and level of residual stress that developed during the AM process. The major issue of any 3D printing system for the fabrication of zirconia parts is the internal (residual) stress, which is formed either during the printing process or during the post-process. The residual stress generated during the post-process includes high-temperature thermal treatment (sintering process) upon cooling or due to the difference in the thermal expansion coefficient (CTE) between the composite material of zirconia/bilayer material [137]. In other words, the mismatch of the CTE of two different materials can induce residual stress (tensile). Correspondingly, it was demonstrated that the selection of slow cooling and firing program of ceramic can potentially reduce the stress, which will also decrease the risk of chipping of porcelain layer in zirconia dental restoration [138]. Moreover, residual stress has a direct effect on the aging process. For instance, the tensile stresses of the zirconia composite can accelerate the aging process of the zirconia parts in body fluids [137]. It can be regulated by the stabilizer material nature and content of the zirconia phase in the composite. The most common diagnostic techniques employed for the residual stress measurements include X-ray diffraction, nanoindentation, Raman spectroscopic analysis, thermal tempering using a two-dimensional (2D) analytical model, and three-dimensional (3D) finite element simulation. However, the magnitude of the residual stress of zirconia parts varies from location to location of geometry. Also, the residual stress distribution is affected by the thickness and geometry of the zirconia parts [139]. Upcoming research should be focused on the residual stress of the AM zirconia parts are need to consider.
4.2 Clinical challenges
Although diverse AM-based research studies claim that zirconia-based scaffolds are practicable, true accomplishments are only determined based on the result of the clinical studies. In this regard, there are many unaddressed areas of applications when applying AM-based zirconia to real-world dental and bone restoration that are unresolved. For example, there are internal defects (cracks, porosity) that are formed during layering/printing or postprinting of the designed zirconia prostheses using AM-based techniques. They could affect the mechanical strength of AM zirconia crowns, bridges, implants, and scaffolds and result in a failure to satisfy the dental and biomedical requirements [57]. Nevertheless, optimum porosity is essential to guide cell adhesion or osteointegration. Hence, the stability among the material properties and biological requests need to be established by optimizing the slurry formulation/feedstock and sintering procedures on whatever AM-based techniques are used. The major challenges of 3D printed dental prostheses for real clinical applications are surface finishing/topography, staircase effects, geometrical overgrowth, and mechanical properties. Specifically, the marginal tolerance requirement (< 0.1 mm) for dental prosthetic applications via AM-based techniques is hard to realize, particularly when material strength and density are also mandatory [54, 140].
Uneven shrinkage is caused by the inbound technical shortage of AM-based techniques. Unresolved accuracy in the z-direction compared to the x and y-directions induces densification of ceramic powders within the layer and related issues (degree of polymerization and layer thickness). Overall, the printing parameters along the z-direction are yet to be optimized in such a way that the dimensional accuracy of the zirconia parts is achieved using AM-based techniques capable of addressing the patient-specific requirements. The technical imperfections in design may lead to plaque accumulation, risk of microleakage, and local inflammation [141, 142]. Thus, the relationship between dimensional precision and clinical adoption is critical to the adoption of any AM-based techniques.
Because the scaffolds need to be in direct contact with biological fluids, parts sterilization is important. Hence, biomedical engineers should be aware of the sterilization requirements while designing zirconia-based parts using AM-based techniques. The scaffolds should not lose their characteristic properties even after sterilization. Limited in vivo studies have been devoted to determining the after-effects of zirconia-based scaffolds on the biological environment. These confirm that the AM-based techniques for zirconia-based ceramics are still in infancy. Hence, biomedical engineers should be conscious of the importance of in vivo studies to realizing the practical applications of zirconia-based scaffolds.
4.3 Industrial (cost and resource) challenges
Leading biomedical implant manufacturing companies including Stryker Corp, ZERAMEX, Straumann ceramic, Nobel Biocare, Zimmer Biomet, Wright Medical, Globus Medical, and Integra Lifesciences focused on developing, manufacturing, and promoting zirconia-based biomedical implants as a material of choice via additive manufacturing technology. Design flexibility, material productivity, and low-volume production feasibility are the prime factors behind the interest in additive manufacturing technology among the leading companies. However, AM-based technologies facing undeniable difficult challenges to fabricate zirconia-based scaffolds. Though adopting AM-based technologies for zirconia implants needs time and determination, the most important challenge lies in the substantial investment on the principal investment cost for the production floor [143]. Investment in the fabrication of zirconia-based biomedical implants from AM-based technologies is not only about equipment cost. It includes the investments in the AM ecosystem as well, which involves material, software, manpower coaching, postprocessing apparatus, documentation, and merging all facilities capable of mass production. More importantly, capital investment and material resources will be added to the above-stated challenges, which is large enough for a corporation to invest in AM as an aggregate. Hence, long-term cost assessment challenges were ahead for any biomedical implant company to unlock the AM-based technology to process zirconia-based scaffolds for wider marketplaces [143].
5. Conclusions
New technologies often mean new construction techniques and material and resource applications. AM has become a potentially vital technology in fabricating zirconia-based materials for various critical-sized applications, including bone scaffolds and dental crowns, bridges, and implants. As both AM-based technology and zirconia-based materials are in their infancy for scaffold application, it is essential to create awareness and sensitization among researchers. For example, among the AM-based technology, very few 3D printing systems (SLA, SLS, and DLP) are successful in manufacturing zirconia-based ceramics as scaffolds in the lab scale itself. This is inadequate when compared to well-established 3D printing systems for the use of metal and polymer materials, hence there is a prolonged difficulty in the clinical accomplishment of zirconia-based scaffolds. Though the mechanical properties of the zirconia parts achieved via 3D printing are comparable to the conventional zirconia parts, still some inbound issues such as internal defects (crack and porosities) and dimensional accuracies need to be enhanced. Moreover, for the enhanced bioactivity of zirconia parts, precise selection of the bioactive material and surface treatment strategies (coating/composite) are still under search. It has to be declared here that the essential printing parameters, materials preparation, and the development of the printer capability are progressively taken care of by the biomedical experts in the recent reports. Hence, collective efforts need to be dedicated in collaboration with academia, AM-machine developers, and clinical end-users to share their materials and design requirements to achieve the expected goals. The collective scientific outcomes, together with materials engineering and manufacturing technology, are extremely important in actualizing any emerging technology. AM-based technology could be utilized for manufacturing zirconia-based ceramics, which would be a milestone for society if all its current limitations can be systematically and creatively addressed.
Acknowledgments
This work was supported by the National Research Foundation of Korea (NRF). Grant funded by the Korean government (MSIT) (No. 2019R1A2C108945613).
Conflict of interest
The authors declare no conflict of interest.
Notes/thanks/other declarations
We thank Pavithra Kumaresan, Karthik Narayanan, and Hariprasath Sekar for their timely help during editing the manuscript.
\n',keywords:"additive manufacturing (AM), zirconia, dental restorations, scaffolds, implants, challenges",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80125.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80125.xml",downloadPdfUrl:"/chapter/pdf-download/80125",previewPdfUrl:"/chapter/pdf-preview/80125",totalDownloads:166,totalViews:0,totalCrossrefCites:1,dateSubmitted:"October 22nd 2021",dateReviewed:"December 12th 2021",datePrePublished:"January 19th 2022",datePublished:null,dateFinished:"January 19th 2022",readingETA:"0",abstract:"Zirconia was established as one of the chief vital ceramic materials for its superior mechanical permanency and biocompatibility, which make it a popular material for dental and orthopedic applications. This has inspired biomedical engineers to exploit zirconia-based bioceramics for dental restorations and repair of load-bearing bone defects caused by cancer, arthritis, and trauma. Additive manufacturing (AM) is being promoted as a possible technique for mimicking the complex architecture of human tissues, and advancements reported in the recent past make it a suitable choice for clinical applications. AM is a bottom-up approach that can offer a high resolution to 3D printed zirconia-based bioceramics for implants, prostheses, and scaffold manufacturing. Substantial research has been initiated worldwide on a large scale for reformatting and optimizing zirconia bioceramics for biomedical applications to maximize the clinical potential of AM. 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Shishkovsky"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Overview of zirconia",level:"2"},{id:"sec_2_2",title:"1.2 Additive manufacturing techniques",level:"2"},{id:"sec_2_3",title:"1.2.1 Single-step process or direct process",level:"3"},{id:"sec_3_3",title:"1.2.2 Multistep or indirect process",level:"3"},{id:"sec_6",title:"2. Formulation and general properties of zirconia directed to biomedical applications",level:"1"},{id:"sec_6_2",title:"2.1 Powder bed method",level:"2"},{id:"sec_6_3",title:"Table 2.",level:"3"},{id:"sec_7_3",title:"2.1.2 Binder jetting (BJ)",level:"3"},{id:"sec_9_2",title:"2.2 Stereolithography",level:"2"},{id:"sec_9_3",title:"2.2.1 Oligomers and monomers",level:"3"},{id:"sec_10_3",title:"2.2.2 Photoinitiator",level:"3"},{id:"sec_11_3",title:"2.2.3 Dispersant",level:"3"},{id:"sec_13_2",title:"2.3 Material extrusion",level:"2"},{id:"sec_13_3",title:"Table 4.",level:"3"},{id:"sec_14_3",title:"2.3.2 Water base",level:"3"},{id:"sec_17",title:"3. Biomedical application of AM zirconia",level:"1"},{id:"sec_17_2",title:"3.1 Dental applications",level:"2"},{id:"sec_17_3",title:"Table 5.",level:"3"},{id:"sec_18_3",title:"Table 6.",level:"3"},{id:"sec_20_2",title:"3.2 Bone-regeneration applications",level:"2"},{id:"sec_22",title:"4. Outlook and prospective",level:"1"},{id:"sec_22_2",title:"4.1 Laboratory challenges",level:"2"},{id:"sec_23_2",title:"4.2 Clinical challenges",level:"2"},{id:"sec_24_2",title:"4.3 Industrial (cost and resource) challenges",level:"2"},{id:"sec_26",title:"5. Conclusions",level:"1"},{id:"sec_27",title:"Acknowledgments",level:"1"},{id:"sec_30",title:"Conflict of interest",level:"1"},{id:"sec_27",title:"Notes/thanks/other declarations",level:"1"},{id:"sec_30",title:"Abbreviations",level:"1"}],chapterReferences:[{id:"B1",body:'Ivanova N, Gugleva V, Dobreva M, Pehlivanov I, Stefanov S, Andonova V. We are IntechOpen, the world’s leading publisher of Open Access books Built by scientists, for scientists TOP 1%. INTECH. 2016;i(tourism):13'},{id:"B2",body:'Dubey N, Ferreira JA, Malda J, Bhaduri SB, Bottino MC. Extracellular matrix/amorphous magnesium phosphate bioink for 3D bioprinting of craniomaxillofacial bone tissue. ACS Applied Materials & Interfaces. 2020;12(21):23752-23763. 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Department of Prosthodontics, Dental Science Research Institute, School of Dentistry, Chonnam National University, Republic of Korea
Chonnam National University Biomedical Evaluation and Research Center, Republic of Korea
Department of Prosthodontics, Dental Science Research Institute, School of Dentistry, Chonnam National University, Republic of Korea
RIS Advanced Center for Biomaterials, School of Dentistry, Chonnam National University, Republic of Korea
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On grounds of above it is implied, the process of solidification constitutes an important aspects in the production of a defect free casting.",book:{id:"10432",slug:"casting-processes-and-modelling-of-metallic-materials",title:"Casting Processes and Modelling of Metallic Materials",fullTitle:"Casting Processes and Modelling of Metallic Materials"},signatures:"Upendra Kumar Mohanty and Hrushikesh Sarangi",authors:[{id:"328540",title:"Prof.",name:"Hrushikesh",middleName:null,surname:"Sarangi",slug:"hrushikesh-sarangi",fullName:"Hrushikesh Sarangi"},{id:"328543",title:"Prof.",name:"Upendra Kumar",middleName:null,surname:"Mohanty",slug:"upendra-kumar-mohanty",fullName:"Upendra Kumar Mohanty"}]},{id:"48856",title:"Silicon Carbide in Microsystem Technology — Thin Film Versus Bulk Material",slug:"silicon-carbide-in-microsystem-technology-thin-film-versus-bulk-material",totalDownloads:2868,totalCrossrefCites:4,totalDimensionsCites:10,abstract:"This chapter looks at the role of silicon carbide (SiC) in microsystem technology. 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Both SiC material forms have played important roles in different microsystem types.",book:{id:"4721",slug:"advanced-silicon-carbide-devices-and-processing",title:"Advanced Silicon Carbide Devices and Processing",fullTitle:"Advanced Silicon Carbide Devices and Processing"},signatures:"Mariana Amorim Fraga, Matteo Bosi and Marco Negri",authors:[{id:"9292",title:"Dr.",name:"matteo",middleName:null,surname:"bosi",slug:"matteo-bosi",fullName:"matteo bosi"},{id:"38456",title:"Dr.",name:"Mariana",middleName:null,surname:"Amorim Fraga",slug:"mariana-amorim-fraga",fullName:"Mariana Amorim Fraga"},{id:"175671",title:"MSc.",name:"Marco",middleName:null,surname:"Negri",slug:"marco-negri",fullName:"Marco Negri"}]},{id:"46237",title:"Corrosion Resistance Through the Application of Anti- Corrosion Coatings",slug:"corrosion-resistance-through-the-application-of-anti-corrosion-coatings",totalDownloads:7361,totalCrossrefCites:11,totalDimensionsCites:32,abstract:null,book:{id:"3817",slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Api Popoola, OE Olorunniwo and OO Ige",authors:[{id:"169258",title:"Dr.",name:"Patricia",middleName:null,surname:"Popoola",slug:"patricia-popoola",fullName:"Patricia Popoola"}]},{id:"46235",title:"Corrosion Detection for Automated Visual Inspection",slug:"corrosion-detection-for-automated-visual-inspection",totalDownloads:3471,totalCrossrefCites:18,totalDimensionsCites:31,abstract:null,book:{id:"3817",slug:"developments-in-corrosion-protection",title:"Developments in Corrosion Protection",fullTitle:"Developments in Corrosion Protection"},signatures:"Francisco Bonnin-Pascual and Alberto Ortiz",authors:[{id:"124589",title:"Prof.",name:"Alberto",middleName:null,surname:"Ortiz",slug:"alberto-ortiz",fullName:"Alberto Ortiz"},{id:"169256",title:"Ph.D. Student",name:"Francisco",middleName:null,surname:"Bonnin-Pascual",slug:"francisco-bonnin-pascual",fullName:"Francisco Bonnin-Pascual"}]}],onlineFirstChaptersFilter:{topicId:"944",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81709",title:"New-Age Al-Cu-Mn-Zr (ACMZ) Alloy for High Temperature-High Strength Applications: A Review",slug:"new-age-al-cu-mn-zr-acmz-alloy-for-high-temperature-high-strength-applications-a-review",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.104533",abstract:"One of the prime challenges with age hardened Al-Cu alloys is the strength degradation at high temperatures (above ∼250°C) due to the coarsening of strengthening θ′ precipitates and associated metastable θ′ → stable θ phase transformation. A recent discovery suggests that micro-alloying with Manganese (Mn) and Zirconium (Zr) can synergistically restrict θ′ precipitate coarsening, thereby rendering an excellent high temperature stability for Al-Cu-Mn-Zr (ACMZ) alloys. The θ′ precipitates are stabilized primarily from the reduction of interfacial energy by preferential solute segregation (Mn & Zr) at θ′ precipitate/α-Al matrix interfaces. The Al-Cu-Mn-Zr alloys thereby exhibit excellent high temperature hardness and tensile properties (yield and ultimate tensile strength) in addition to superior fatigue life and creep resistance. This newly developed Al-Cu-Mn-Zr alloys also showed excellent hot tearing resistance compared to the conventional cast Al-Cu alloys so much so that it meets the industrial standards as well. These alloys also have promising manufacturing possibility by additive route. Overall, Al-Cu-Mn-Zr alloys offer great potential for the automotive industry because of their unprecedented high temperature performance which should enable engineers to build light weight passenger vehicles leading to a safer and greener environment.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Samarendra Roy and Shibayan Roy"},{id:"80372",title:"Application of the Aluminothermic Reduction Process for Magnesium Removal in Aluminum Scrap",slug:"application-of-the-aluminothermic-reduction-process-for-magnesium-removal-in-aluminum-scrap",totalDownloads:16,totalDimensionsCites:0,doi:"10.5772/intechopen.102407",abstract:"Magnesium is considered as impurity element in aluminum recycled for obtaining some cast alloys, with low concentration Mg, because at 0.1 wt% results in fragility, fractures, and defects. This research applies the aluminothermic reduction process to decrease magnesium content in aluminum cans by adding ZnO, to produce reaction products solid-state (Al2O3, MgO and MgAl2O4), and there is a possibility to obtain Al-Zn alloy. The conditions of the process were, melting temperature (750, 800, 850°C) and stirring velocity (200, 250, 300 rpm). The Mg and Zn contents were measured for chemical analysis and scrap generated from every process was analyzed by X-ray diffraction. The results show how the aluminothermic reduction decreased Mg from 0.93 to 0.06 wt% and increased zinc up to 5.52wt % in the molten metal. Therefore, this process can be used to remove Mg and can also prevent the generation of polluting gases into the environment.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Rocio Maricela Ochoa Palacios, Citlaly Castillo Rodriguez, Jesus Torres Torres, Perla Janet Resendiz Hernandez and Alfredo Flores Valdes"},{id:"80920",title:"Drilling of 7075 Aluminum Alloys",slug:"drilling-of-7075-aluminum-alloys",totalDownloads:51,totalDimensionsCites:0,doi:"10.5772/intechopen.102864",abstract:"Aluminum alloy (Al 7075) has been increasingly used as structural components in automotive and aerospace industry due to their low density, high strength and good corrosion resistance compared with other metals. To manufacture and assemble the components, drilling operations are often conducted. However, Al 7075 is ductile and soft, which causes difficulty in drilling, resulting in material adhesion, high tool wear, short tool life and poor hole quality. As a result of the poor hole quality, there is a high percentage of part rejection, which can increase the manufacturing time and cost. This chapter discusses challenges and techniques to drill Al 7075 in terms of the cutting parameters and drilling conditions to prolong the tool life and achieve good hole quality. Drilling experiments on Al 7075-T6 (heat-treated) were conducted using carbide cutting tools at various cutting parameters. Reducing cutting speed and increasing feed rate resulted in reducing tool wear, whereas a reduction in surface roughness, hence improved machined surface finish, was found when both cutting speed and feed rate were reduced in drilling Al 7075-T6. Producing good hole quality is vital during the drilling process to ensure a good assembly and product service performance.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Aishah Najiah Dahnel, Mohamad Noor Ikhwan Naiman, Muhammad Azim Mirza Mohd Farid, Ahmad Faris Abdul Rahman and Nur Munirah Meera Mydin"},{id:"79869",title:"Assisting Liquid Phase Sintering of Pure Aluminum (Al) by the Tin Addition",slug:"assisting-liquid-phase-sintering-of-pure-aluminum-al-by-the-tin-addition",totalDownloads:102,totalDimensionsCites:0,doi:"10.5772/intechopen.101507",abstract:"In the present study, the addition of tin (Sn) to the pure Al system was done, and its effects on the morphology, density, and compressive yield strength of pure Al were analyzed systematically. In this context, the morphology of sintered Al revealed enhanced wettability and sintering response between Al particles with increased Sn content. Moreover, physical characteristics of sintered Al alloys demonstrated oxidation phenomenon (black color specimen) with the lowest Sn content of 1.5 weight percent (wt.%), in which a higher Sn content of 2 and 2.5 wt.% produced silver color specimens, implying a reduction in oxidation. Additionally, densification of sintered Al alloys was greatly promoted with increased Sn contents, suggesting effective wetting as confirmed by the previous morphological observations. Similarly, the compressive yield strength of sintered Al alloys improved with increased Sn content which might be due to the enhanced inter-particle contacts between Al particles and sufficient wetting by molten Sn. Based on the results obtained, the introduction of Sn powder at various contents improved the sintering response of pure Al powder by providing sufficient liquid-phase sintering. Therefore, the sintered Al alloys had enhanced the morphological, densification, physical characteristics, and compressive yield strength.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Nur Ayuni Jamal, Farazila Yusof, Yusilawati Ahmad, Norhuda Hidayah Nordin and Suraya Sulaiman"},{id:"79459",title:"Characteristics of Al-Mg Test Pieces with Fe Impurities Fabricated by Die Casting, Roll Casting, and Hot Forging",slug:"characteristics-of-al-mg-test-pieces-with-fe-impurities-fabricated-by-die-casting-roll-casting-and-h",totalDownloads:64,totalDimensionsCites:0,doi:"10.5772/intechopen.100940",abstract:"The suitability of Al-Mg alloys for recycling was investigated using energy-saving processes. The Al-Mg alloy is a non-heat-treatable alloy and has the advantage of energy saving in comparison with heat-treatable alloys. Al-Mg alloys with Mg contents ranging from 4.5–10% were tested. Die casting, cast-forging, and roll casting were selected as energy-saving processes, as they have the advantage of process saving. A single-roll caster equipped with a scraper was used as the roll-caster. Fe was added to the Al-Mg alloys at contents of 0.2%, 0.4%, 0.6%, and 0.8% to model recycled alloys used in automobile manufacture. In the selected processes, the tensile stress and 0.2% proof stress of the Al-Mg alloys were little influenced by the added Fe content, whereas the elongation tended to decrease as the Fe content increased. The process influenced the degree to which the Fe content affected the elongation, and it was found that a suitable Mg content for recycling depends on the target process.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Toshio Haga"},{id:"79154",title:"Development and Characterization of New Functionally Graded Aluminium Alloys",slug:"development-and-characterization-of-new-functionally-graded-aluminium-alloys",totalDownloads:108,totalDimensionsCites:0,doi:"10.5772/intechopen.101022",abstract:"Nowadays, aluminium alloys are adopted mainly to produce engineering and automotive components. The present investigation aims to design, cast and characterize novel functionally graded materials (FGMs) produced using Al-Mg and Al-Si alloys by gravity casting technique. Alloys were sequentially cast into a mould to obtain an FGM to realizing great mechanical and metallurgical bonding. Zn addition was further performed in FGM to increase the mechanical properties, thanks to the nucleation of the intermetallic phases MgZn2. Castings were subsequently mechanically tested by tensile tests, bending tests, hardness and microhardness measures to assess the products\\' quality. Microstructural characterizations were performed along the FGM to assess the metallurgical bonding and evaluate the microstructures obtained. Fracture, microstructural and compositional analysis will highlight the quality of this new FGM proposed. Possible applications of these materials are suggested, as automotive pistons or structural components.",book:{id:"10847",title:"Aluminium Alloys - Design and Development of Innovative Alloys, Manufacturing Processes and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/10847.jpg"},signatures:"Elisa Fracchia and Mario Rosso"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:320,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"June 25th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). He was the head of the undergraduate program in Biomedical Engineering of the Federal University of Uberlândia (2015 - June/2019) and the head of the Centre for Innovation and Technology Assessment in Health (NIATS/UFU) since 2010. He is the head of the Postgraduate Program in Biomedical Engineering (UFU, July/2019 - to date). He was the secretary of the Parkinson's Disease Association of Uberlândia (2018-2019). Dr. Andrade's primary area of research is focused towards getting information from the neuromuscular system to understand its strategies of organization, adaptation and controlling in the context of motor neuron diseases. His research interests include Biomedical Signal Processing and Modelling, Assistive Technology, Rehabilitation Engineering, Neuroengineering and Parkinson's Disease.",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",isOpenForSubmission:!0,editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",slug:"luis-villarreal-gomez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",biography:"Dr. Luis Villarreal is a research professor from the Facultad de Ciencias de la Ingeniería y Tecnología, Universidad Autónoma de Baja California, Tijuana, Baja California, México. Dr. Villarreal is the editor in chief and founder of the Revista de Ciencias Tecnológicas (RECIT) (https://recit.uabc.mx/) and is a member of several editorial and reviewer boards for numerous international journals. He has published more than thirty international papers and reviewed more than ninety-two manuscripts. His research interests include biomaterials, nanomaterials, bioengineering, biosensors, drug delivery systems, and tissue engineering.",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:23,paginationItems:[{id:"82392",title:"Nanomaterials as Novel Biomarkers for Cancer Nanotheranostics: State of the Art",doi:"10.5772/intechopen.105700",signatures:"Hao Yu, Zhihai Han, Cunrong Chen and Leisheng Zhang",slug:"nanomaterials-as-novel-biomarkers-for-cancer-nanotheranostics-state-of-the-art",totalDownloads:23,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11405.jpg",subseries:{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering"}}},{id:"82184",title:"Biological Sensing Using Infrared SPR Devices Based on ZnO",doi:"10.5772/intechopen.104562",signatures:"Hiroaki Matsui",slug:"biological-sensing-using-infrared-spr-devices-based-on-zno",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hiroaki",surname:"Matsui"}],book:{title:"Biosignal Processing",coverURL:"https://cdn.intechopen.com/books/images_new/11153.jpg",subseries:{id:"7",title:"Bioinformatics and Medical Informatics"}}},{id:"82122",title:"Recent Advances in Biosensing in Tissue Engineering and Regenerative Medicine",doi:"10.5772/intechopen.104922",signatures:"Alma T. Banigo, Chigozie A. Nnadiekwe and Emmanuel M. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. 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Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[{type:"book",id:"11672",title:"Chemokines Updates",subtitle:null,isOpenForSubmission:!0,hash:"c00855833476a514d37abf7c846e16e9",slug:null,bookSignature:"Prof. Murat Şentürk",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",editedByType:null,submissionDeadline:"May 6th 2022",editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:320,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/318353",hash:"",query:{},params:{id:"318353"},fullPath:"/profiles/318353",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()