Change from three times a week on‐line haemodiafiltration (OL‐HDF) to short daily on‐line haemodiafiltration (D‐OL‐HDF): comparison of urea kinetics during the two study periods.
\r\n\tNotably, the book encourages academic scholars and researchers to contribute to the modern concepts of CSR. Fundamentally, it speaks for well-developed literature for entrepreneurs and managers, thus assisting them in the decision-making process.
\r\n\tFurthermore, this book is of great value to policymakers, practitioners, and corporations, thus contributing to various disciplines (e.g., social science and management).
\r\n\tThese proposed themes encourage future researchers and professionals to share their ideas, concepts and work concerning these subject domains. All these suggested topics had recommended under the rubrics of CSR. Perhaps, all the professionals, researchers, and scholars are welcome to submit their piece of work, in particular to the suggested topics.
\r\n\tIndeed, the recommended topics include the following but are not limited to these only.
\r\n\t• Corporate Governance and Sustainability
\r\n\t• Green Innovation and CSR
\r\n\t• Social Entrepreneurship
\r\n\t• Green Economy and Social and Environmental Sustainability
\r\n\t• Sustainable Development and Industrialization
Haemodialysis treatment has changed the lives of millions of patients around the world who have advanced kidney disease. The treatment has advanced considerably since the first treatment on a human, lasting just 15 minutes and performed by George Haas in Giessen, Germany, in October 1924 [1]. It was not until the 1960s when maintenance haemodialysis really started and at present, over 90 years since Haas, there are over 400,000 prevalent users in the USA alone [2]. Dialysis provides a bridge to transplantation for some, and for others, it allows survival when residual kidney function is no longer sufficient to sustain life. While the survival of patients has improved since the early days of its inception, the survival of haemodialysis patients remains unacceptably poor. In the United Kingdom, 18% of those aged 65–74 starting haemodialysis will not survive 1 year [3]. Five‐year survival data has often been compared to those of patients with cancer to make the figures more tangible. With recent figures showing 50% survival at 5.8 years in the 55–64 years group [4], it is not hard to see why this comparison is made. Clearly, one of the key challenges for the nephrology community is to change this unacceptably high mortality rate. In addition to this, there are many other factors that make a large difference to the patient in front of us, and arguably, these are as important to address and considerably improve.
\nThe aim of haemodialysis is to replicate normal physiology as much as possible. Although this may sound straightforward initially, there are a vast array of factors to consider. The ideal treatment should give good survival rates, prevent cardiovascular events and hospitalizations, effectively manage fluid and salt balance and address the anaemia and mineral‐bone disorder associated with chronic kidney disease (CKD). Patient well‐being, cognition, sleep, the ability to work and nutritional status are also hugely important factors which need addressing and the list could continue. For a treatment, which for the majority of patients is performed for 12 hours of the week (just 7% of the week in terms of time), this is an incredibly tall order and it is not entirely surprising that outcomes remain poor.
\nConventional haemodialysis (CHD) is the most common treatment schedule and lasts for 3–4 hours thrice weekly. This treatment mainly takes place in a hospital or in a dedicated dialysis unit. Other treatment regimes include short daily haemodialysis (SDHD), which is performed for 1.5–3 hours 5–7 times per week, long nocturnal daily haemodialysis (LNDHD) which is performed for 6–8 hours 5–7 times per week and long conventional haemodialysis (LHD), which is typically 8 hours 3 times per week.
\nAlthough CHD is the most common treatment regime now, LHD was the most common treatment initially in the 1960s [5]. This treatment came about purely by convention. Home haemodialysis in the United Kingdom was started in London in 1964 by Shaldon and his team [6] and expanded following this. Home haemodialysis was necessary as hospital facilities were sparse, treatment times were lengthy and home dialysis offered both financial and logistical benefit. Prevalence in the United Kingdom peaked in 1982 when 62% of HD patients were at home [3]. As dialysis treatment time shortened and patient numbers increased, haemodialysis practice changed from a predominantly home‐based therapy to a predominantly hospital‐based therapy.
\nThe National Cooperative Dialysis Study (NCDS) (
It would seem therefore that with
Based on all of this, a strong argument can be made to further explore more frequent and extended haemodialysis treatments.
\nThe basic principle behind dialysis is the removal of solutes across a semipermeable membrane. Haemodialysis relies on the process of diffusion where solutes move from an area of high concentration to an area of low concentration. Solutes pass from the patients’ blood to the dialysis fluid across the dialysis membrane in this manner. The concentration gradient is maintained by the countercurrent flow of dialysate and blood and the maintenance of adequate blood and dialysate flow.
\nHaemofiltration allows the clearance of larger molecules through the process of convection. A hydrostatic pressure gradient is used to pass the patient\'s blood across a membrane with a large pore size. Solutes follow water through a process called “solvent drag” [12]. Large volumes of fluid are typically filtered and a replacement fluid is required, which enters the dialysis circuit and is mixed with the patient\'s blood before it is returned.
\nHaemodiafiltration (HDF) combines the techniques of both haemodialysis and haemofiltration. Solutes are cleared by both diffusion and convection, thus allowing more efficient clearance of both small and middle molecules. The replacement fluid can either be obtained from pre‐prepared bags or prepared “online” by the machine (OL‐HDF), which is able to produce ultrapure fluid. This dialysis therapy has a number of potential advantages, which are discussed in more detail later in this chapter.
\nβ‐Trace protein, cystatin‐C and B2M are all middle MW molecules that are freely filtered, resorbed and catabolized in the tubular cells. A study by Lindström et al. [16] has shown clear differences in the clearance of these molecules by different dialysis modalities—CHD did not change the concentrations of any of these proteins while in HDF both cystatin C and B2M were reduced and β‐trace protein was only reduced in HDF. This demonstrates a clear difference between dialysis modalities in terms of clearance and a clear biomarker that could be measured. Moreover, β‐trace protein had been found to be an independent predictor of both death and cardiovascular mortality in haemodialysis patients [17]. The use of such molecules could be part of the way that we assess haemodialysis adequacy in the future and tailor treatment to the patient.
\nThe specifications of dialysis membranes have improved considerably. The use of cellulose‐based membranes were common initially; however, they were associated with complement and leucocyte activation [18] resulting in dialyser reactions. The majority of dialysis membranes in use now are synthetic and are more biocompatible—reactions can still occur however and anaphylactoid reactions have been reported, particularly in patients on ACE inhibitors [19]. More recently, dialysis membranes have been manufactured with larger pore sizes to allow a higher ultrafiltration rate and allow clearance of larger molecules. Membranes can be classified as high flux or low flux and for the purposes of the HEMO study [20] were defined as B2M clearances of <10 ml/min for low flux and >20 ml/min for high flux. High‐flux membranes have been found to lower pre‐dialysis B2M concentrations [21] and may prevent dialysis‐related amyloidosis [22]. Several observational studies have identified a survival benefit with high‐flux dialysers [23, 24]. Although the HEMO study showed no benefit from high‐flux membranes, the study may not have been sufficiently powered to detect a significant benefit [25]. The subsequent European study, the MPO Study [26], showed survival benefit to those patients with a serum albumin of <40 g/l. Several guidelines now recommend high‐flux dialysers including the European Renal Association [27] and practice has also changed considerably.
\nThe production of a high‐quality infusion fluid is of paramount importance in HDF. More than 20 litres of infusion fluid can be administered to the patient during a typical HDF session and thus ultrapure water and dialysis fluid are required. Ultrapure water is defined by the standard for replacement fluid requiring <0.1 colony‐forming units (CFU)/ml and an endotoxin concentration <0.03 endotoxin unit (EU)/ml [28]. The use of ultrapure dialysis fluid is associated with a reduction in inflammatory markers and an improvement in serum albumin, haemoglobin and ferritin [29].
\nThe seminal paper in 1992 by Bernard Charra and his group in Tassin, France, showed hugely impressive survival rates of their haemodialysis patients of 87% at 5 years and 43% at 20 years, which far surpassed matched patients on both European and US registries. All patients received 8 hours of haemodialysis three times per week (LHD). It is likely that the survival association is related to achieving good blood pressure control (antihypertensives were seldom required in the group) through optimized ultrafiltration and the enhanced clearance of uraemic toxins provided by the longer treatment. Their publication sparked interest once again in extended haemodialysis. With the continued increasing demand for renal replacement therapy and limited resources in hospitals, novel ways of providing haemodialysis were required. Home haemodialysis seemed an attractive option and could also accommodate more frequent and extended schedules. The first daily nocturnal haemodialysis programme was set up in Toronto in 1994 [30].
\nThe prescription of home haemodialysis in the United Kingdom remains very variable; however, the most common prescription in 2009 was still 4 hours thrice weekly (51.9% of home HD patients), followed by alternate day dialysis (20.5%), short daily (17.4%) and nocturnal (2.9%) [31]. This is a surprising finding given the benefits of more frequent and extended haemodialysis (which we will now expand on). This does however reflect patient choice and the comfort of both patients and clinicians with a CHD schedule.
\nSeveral benefits have come to light from more frequent and extended haemodialysis and these will be outlined in this section.
\nObservational studies show a significant mortality benefit associated with home haemodialysis, even when adjustments are made for age and comorbidity [32]. These findings are also apparent in studies in Australia and New Zealand [33], which have a higher uptake of home haemodialysis. Figures of 90% survival at 5 years and 45% at 20 years have been quoted [34]. Figure 1 shows a clear survival advantage to home haemodialysis over both peritoneal dialysis and facility‐based HD. These data have to be interpreted with care given the high number of confounders. Patients selected for home haemodialysis are generally younger with a low comorbidity burden. They are usually highly motivated and take an interest in their healthcare.
\nThe frequent haemodialysis network (FHN) trials were setup to give a more definitive answer to the benefits of more frequent and extended haemodialysis [35, 36]. The SDHD arm of the trial randomized 245 patients to either frequent (6 times per week) or conventional haemodialysis and the nocturnal arm randomized 87 patients to either CHD or LDNHD. Two coprimary composite endpoints were used—death or change in LV mass or death or change in physical‐health composite score. There was a favourable outcome with regard to both coprimary endpoints for the SDHD trial but not with the LNDHD trial. Looking purely at survival, there was no significant benefit from either trial. With a 12‐month follow‐up period and the numbers involved with the trials, they were not powered to detect an effect on mortality. The question therefore still remains unanswered as to whether more frequent and extended haemodialysis does have a favourable effect on survival.
\nThe survival of home HD patients in New Zealand compared with facility HD and peritoneal dialysis (PD). Image adapted from Marshall et al. [
There is an associated reduction in cardiovascular‐related admissions in converting patients from CHD to LDNHD [37]. There are also fewer cardiovascular‐associated hospital admissions associated with SDHD compared with matched CHD; however, all‐cause hospitalizations remain unchanged [38]. The FHN studies once again showed no change in the rate of hospitalizations.
\nThere is a strong association between a high ultrafiltration rate (>10 ml/kg/hour) and mortality [39, 40]. Chronic fluid overload contributes to an increased LV mass and congestive cardiac failure [41] and this is likely to be highly significant in terms of cardiovascular morbidity and mortality. Increasing haemodialysis treatment time improves the tolerance of ultrafiltration [42, 43]. There are also many reports of improved blood pressure control both in LNHD and in SDH [44–46] and a regression of left ventricular hypertrophy [47]. It has also been shown that ejection fraction, in those with heart failure, can be improved through more frequent haemodialysis and ultrafiltration [48]. With CHD, it often the case that dry weight is not achieved. Patients that experience hypotension during haemodialysis often have their ultrafiltration stopped, receive saline infusions and thus never achieve their dry weight and in fact can exacerbate the situation further. Extended dialysis allows much lower ultrafiltration rates and thus less haemodynamic disturbance. It is likely the effect that extended dialysis has on blood pressure goes beyond the optimization of volume status. When compared to patients on CHD, some patients with a high extracellular volume (measured by bioimpedance) but on extended haemodialysis achieve normotension [49]. A theory put forward for this phenomenon is that extended haemodialysis may lead to efficient removal of vasoactive factors that contribute to hypertension.
\nIncreasing haemodialysis frequency provides more efficient clearance of small MW molecules. It provides a lower peak urea, lower mean urea and less fluctuation [50]. This provides a lower time‐averaged concentration (TAC). Looking purely at
There is a clear association between raised serum phosphate and adverse cardiovascular outcomes in patients with CKD [51, 52]. Conventional haemodialysis does provide sufficient phosphate removal for western diets, and as a result, there is a net phosphate gain [53]. As a result of this, multiple phosphate binder tablets are often required to reduce the absorption of phosphate from the gut. On average, haemodialysis patients have an average pill burden of 19 pills per day and many of these are phosphate binders [54]. A higher pill burden in this setting is associated with lower quality of life scores [54].
\nPhosphate removal on haemodialysis has been found to be time dependent [55] and thus is significantly enhanced in NHD. Phosphate removal is also increased by SDHD but not to the same extent as NHD [56]. In LNDHD, many patients will discontinue their phosphate binders [57] and some require supplementation that can be added to the dialysate [58].
\nReports are mixed when it comes to more frequent haemodialysis and anaemia management. Reduced erythropoietin doses have been reported when patients switch to SDHD from CHD [59] and in NHD [60]. One of the theories put forward for this change is the control of inflammation and reduction in IL‐6 levels which improve erythropoietin responsiveness [61]. The exact effect that more frequent or extended dialysis has on anaemia, however, is still unclear. Again both FHN studies showed no effect on erythropoietin dose.
\nHome haemodialysis allows patients the independence to fit their dialysis treatment around their lifestyles. One may expect this to bring significantly improvements to quality of life; however, this may be offset by the burden of having to perform the treatment so frequently, which can lead to burnout or the increased burden on carers. While there are many reports of improvements in quality‐of‐life measures from switching to NHD [62] or SDHD [63], some show only small improvements in kidney‐specific measure of quality of life [64], while others show no difference. Larger studies have shown a reduction in depressive symptoms related to increased dialysis frequency [65].
\nData from the recent FHN daily trial showed a significant increase in quality‐of‐life score in the SDHD group [35] with no specific benefit from NHD over CHD at home. In the FHN NHD arm, however, both groups had an increase in their quality‐of‐life score showing the positive effect that the setting of the haemodialysis treatment has on this outcome [36] regardless of prescription. Perceived burden on unpaid carers is high among HD patients [66]; however, the FHN trials did not show a higher perceived burden with either SDHD or LDNHD [67].
\nThe patient‐reported experience on both LDNHD and SDHD has been positive in terms of physical, psychological and lifestyle aspects [68]. There is also an associated faster recovery time with home haemodialysis [69]. Once again, it is fair to say once again that the jury is still with regard to whether these treatments truly impact on quality of life. In general, the effect seems to be positive with a paucity of data suggesting a negative impact.
\nIntensive dialysis has been used very successfully in pregnancy. A case series from Canada [70] shows a markedly improved live birth rate and duration of pregnancy with a dose response between dialysis and pregnancy outcomes. Women who had >36 hours of dialysis per week had significantly improved live birth rates (85 vs. 45% in those who had <20 hours of dialysis per week), which again demonstrates and gives strength to high‐dose dialysis.
\nWhile there are many advantages of home haemodialysis, the treatment is not suitable for all patients and it is not a treatment without disadvantages. Although exceedingly rare, there is always the possibility that human error can occur resulting in significant blood loss through a variety of mechanisms. There are reports of patient deaths from exsanguination while on home haemodialysis [71]. The sophistication of safety mechanisms is continually improving to make this event less likely with blood leak detectors, pressure monitoring and line disconnect detectors featuring on newer machines.
\nA clear finding from the FHN trial was an increase in interventions needed for vascular access with 47% of the frequent dialysis group requiring intervention compared with 29% in the CHD group. Interventions to fistulas were required much more often than in catheters. This was not an entirely surprising finding given the considerably increased use of vascular access form more frequent haemodialysis. A solution to this could be the use of a buttonhole technique for fistula cannulation or using single‐needle haemodialysis to reduce the number of needling events. The evidence, however, is not there to support this practice and a systematic review of buttonhole cannulation in home haemodialysis patients found an increase in infectious events, an increase in staff support required and no reduction in surgical interventions compared with the “rope ladder” technique [72]. The FHN nocturnal trial used single‐needle haemodialysis, and despite this, there was still a trend towards increased vascular interventions in this group.
\nFinally, globally, the uptake of extended higher frequency haemodialysis remains low, despite a range of benefits and favourable health economics. There can be major patient and clinical factors driving modality uptake. A key determinant, however, is patient motivation and choice. Extended time or frequency on home HD may add to patient and carer burden and is therefore often perceived as a barrier limiting its uptake.
\nHaemofiltration allows clearance of solutes of up to 20 kDa through the process of convection as previously described. Large volumes of replacement fluid are required for the treatment, and this can be administered either before the filter (pre‐dilution) or after the filter (post‐dilution). Newer technology also allows a mix of pre‐ and post‐dilution or mid‐dilution in an attempt to gain the advantages of both pre‐ and post‐dilution (largely the anticoagulant requirement) [73].
\nConventional HDF provides enhanced B2M clearance compared with HD [74]. It is associated with a reduction in pro‐inflammatory cytokines such as IL‐6 and TNF‐α [75] and reduced episodes of hypotension during treatment [76]. There does not appear to be a benefit in terms of left ventricular mass, pulse wave velocity or ejection fraction [77]. This could be due to achieving low substitution volumes or large interdialytic fluid shifts induced by conventional thrice‐weekly schedule.
\nThere have been three recent large prospective clinical trials, which have compared HDF with high‐flux HD with contrasting results. The ESHOL study [78], a Spanish study, showed promising results with a 30% lower all‐cause mortality, a 33% lower cardiovascular mortality and 55% lower infection‐related mortality compared with haemodialysis. A Dutch study [79] showed no difference in outcome between HDF and HD and a Turkish [80] study drew the same conclusion. Looking back at these studies, the ESHOL study achieved the highest convective volumes (22.9–23.9 l per session) and
In order to provide HDF with high convection volumes, large volumes of sterile replacement fluid are required (>15 l), which would not be practical with pre‐packaged solutions. Instead of online preparation of fluid, which is the most practical solution, HDF uses an additional 50–80 l of water per session [81] (with a typical haemodialysis session using around 500 l of mains water to generate dialysate [82]). Ultrapure dialysate must be generated by the machine to the standards previously described.
\nThere appears to be a benefit from high convective volume haemodiafiltration. The biggest determinants to achieving a high convective volume are treatment time and blood flow [83]. A blood flow between 360 and 500 ml/min is required to achieve the necessary transmembrane pressure [84]. A well‐functioning vascular access would therefore also be required. Although there are reports of achieving a convective volume of >20 l with a haemodialysis catheter, a well‐functioning AV fistula would allow higher blood flows [84].
\nGiven that treatment time is clearly an important factor in achieving the dose of HDF associated with improved outcomes, the home setting is an ideal place to deliver the treatment. Vascular access would not be a barrier and combining frequent haemodialysis with a convective treatment should maximize middle molecule clearance. Switching patients from a conventional HDF schedule to a short daily schedule has been reported to result in a higher removal of middle and large molecules, a reduction in phosphate binders, the disappearance of post‐dialysis fatigue, an improvement in nutritional status as well as a 30% reduction in left ventricular mass [85]. The improvements in switching to more frequent OL‐HDF are outlined in Table 1.
\n\n | Baseline | \nMonth 3 | \nMonth 6 | \n
---|---|---|---|
sp | \n2.30 ± 0.20 | \n1.13 ± 0.15b | \n1.11 ± 0.11b | \n
e | \n1.96 ± 0.17 | \n0.90 ± 0.12b | \n0.88 ± 0.08b | \n
URR | \n84.3 ± 2.5 | \n64.2 ± 5.3b | \n63.3 ± 4.2b | \n
Weekly sp | \n6.90 ± 0.59 | \n6.78 ± 0.91 | \n6.67 ± 0.64 | \n
Weekly e | \n5.88 ± 0.52 | \n5.39 ± 0.75a | \n5.30 ± 0.50a | \n
EKR | \n19.2 ± 0.5 | \n24.2 ± 2.6b | \n23.8 ± 1.9b | \n
std | \n2.62 ± 0.1 | \n3.87 ± 0.3b | \n3.86 ± 0.2b | \n
Weekly URR | \n253 ± 7.5 | \n385 ± 32b | \n380 ± 25b | \n
Change from three times a week on‐line haemodiafiltration (OL‐HDF) to short daily on‐line haemodiafiltration (D‐OL‐HDF): comparison of urea kinetics during the two study periods.
a:
b:
Adapted from Maduell et al. [85].
Abbreviations: URR, urea reduction ratio; sp
While the technology to provide HDF in the home setting exists, it is not widely used at present and there is very little published literature about HDF as a home therapy. Until recently, there have not been haemodialysis machines specifically manufactured for the home market. As a result, patients have been trained on the machines used in the main dialysis unit. Using the same technology both in the home and in the main dialysis unit makes the logistics of maintenance much easier. The health care team, including the technicians, are often more comfortable and experienced using and providing support for a single machine. As technology has developed and haemodialysis machines have become more advanced, it is important that more user‐friendly technology, specifically for the home market, is developed. This will allow further uptake and expansion of home dialysis programmes.
\nThe ideal home HD machine has been described [86] as one which is fast and easy to setup, allows a range of prescriptions (such as short daily and nocturnal), teaches and interacts with the patient and allows the patient to deliver intravenous fluid at the push of a button. The description suggests the ability of the machine to re‐use blood sets and dialysers, prepare all fluids to a standard beyond ultrapure and have the ability to provide HDF. There are many machines in development and it is likely that this “ideal machine” will be in existence in the near future. There is the potential for HDF machines to be complex given the choice in pre‐dilution, post‐dilution and mixed dilution and the blood and dialysate flow. Technology should strike a balance, remaining simple for safe use with minimal margin for error and fast training times but also allow some flexibility to tailor treatment.
\nAs previously described, providing a high water quality is of great importance given the high volume that is infused into the patient. The body of evidence to support the use of ultrapure water really lies in convective treatments, and thus, an essential requirement for any home HDF programme will be the production of ultrapure dialysate. Water may contain both chemical and microbiological contaminants, and in the home setting, this is likely to vary considerably depending on the local feed water. A variety of contaminants can have clinical consequences, such as chloramines, leading to haemolytic anaemia [87], calcium and magnesium contributing to a “hard water syndrome” [88] and nitrates [89], zinc [90] and fluorides [91] have all been documented to have potential clinical effects. After initial assessment of the feed water and the subsequent installation of the filters and water softeners, a surveillance programme for chemical contaminants, endotoxins and bacteria is important. This logistics of such a programme needs to be considered as the sampling protocol, laboratory protocols and the transport and storage of samples must all be carefully planned.
\nMicrobiological contamination can still theoretically occur. Reverse osmosis units filter out substances with a molecular weight > 200 kDa and thus bacterial fragments and small endotoxins can still pass through [92]. Vigilance must be employed for unexplained febrile episodes or signs of chronic inflammation. This would apply to both home haemodialysis and haemodiafiltration.
\nPortability is an important factor for dialysis patients. Peritoneal dialysis has provided a treatment that can be carried out virtually anywhere making the treatment appealing for patients who work or need to travel. To date, the quantity of water and the size of the water treatment devices has limited the portability of haemodialysis. Increasingly, there are haemodialysis machines that allow portability by utilizing sorbent technology to purify water and thus reduce water requirements [93]. With the high convective volumes required for adequate HDF, water requirements remain high and thus limit portability. Developments in this area are needed allow to make HDF a more appealing home treatment for patients. Water use must be minimized and where possible, water should be recycled. Water rejected from reverse osmosis units can be recycled and used elsewhere in the home or dialysis unit and this is being increasingly utilized [82].
\nAnticoagulation must be a major consideration for any extracorporeal dialysis therapy. Many patients on home haemodialysis manage well with the administration anticoagulation, and unfractionated heparin and low molecular weight heparin are in common use. These strategies can also be used in HDF and should not pose a barrier to home HDF use. HDF may allow dialysis without anticoagulation through the use of pre‐dilution HDF. This may be particularly helpful in patients with prolonged bleeding or intolerances to anticoagulation.
\nToday\'s dialysis technology enables HDF to be delivered in the home setting safely with the production of ultra‐pure dialysate and detection of venous dislodgement. There is a growing experience of centres using this technology [94] with a positive experience. Further details on optimal heparinization regimes, water quality variability and its surveillance in home HDF are necessary to define best clinical practice. It is likely that new technology coupled with increasing HDF uptake in dialysis centres will lead on to increasing use of HDF at home.
\nHaemodialysis treatment in general is very costly, and in the United Kingdom, 1–2% of the National Health Service budget is spent on renal care with only 0.05% with ESRF [95]. After consumables, a large proportion of the cost is made up of direct nursing care and transportation [96] (both of which are considerably less in home haemodialysis). Home haemodialysis has been estimated to cost over a third less than hospital‐based haemodialysis in the United Kingdom [96] and frequent home haemodialysis has been shown to offer a cost saving in both Canada and Australia too [97].
\nIn addition to the reduced transport and nursing costs, savings are also offered from a reduction in hospital admissions [37] and a reduction in medication costs (particularly phosphate binders) [98].
\nThe initial setup costs of home haemodialysis are high due to the cost of training, the equipment and installation. These initial costs are usually paid back by 14 months after which savings occur [99], making home haemodialysis an attractive option not only from the clinical benefits but also from the cost‐saving aspect.
\nCosts of high‐flux dialysers have also reduced considerably over time and high‐flux haemodialysis is now the common standard care. A UK Study looked at the costs of 34 patients switching to OL‐HDF and 44 who remained on high‐flux HD. The cost of the treatment was either more expensive or cheaper depending on the choice of blood lines. There was a cost saving in the OL‐HDF group in terms of phosphate binders. Lebourg et al. [81] looked at >28,000 dialysis treatments in a single centre and once again HDF was found to be either cheaper or more costly (-€1.29 to +€4.58 per session) depending on treatment variables selected. It is clear that from a cost perspective, there is little difference between HDF and high‐flux HD.
\nHome haemodialysis provides a convenient and clinically effective way of providing both frequent and extended haemodialysis treatment. Although the hard outcome data for survival from prospective randomized trials are lacking, it is unlikely that a larger, adequately powered trial with sufficient follow‐up time will be feasible and the answer may need to come from registry data. It is also time to look beyond urea clearance and towards markers, such as convective volume and β‐trace protein, as this may pave the way to further improve haemodialysis care in the future.
\nHowever, it is clear that there are a number of clinical benefits from more frequent and extended haemodialysis and aside from this, home haemodialysis is a treatment preferred by many patients if choices are given [100] and a treatment that is associated with an increased satisfaction [101].
\nHDF is also a feasible treatment in the home setting and is already in use. There is growing evidence from randomized trials that dialysis patient outcomes may be improved by high‐frequency HD and by using HDF with high convective volumes. Combining increased frequency HD with convective treatment would give patients the benefits of both small and middle MW clearance without additional patient burden or cost implications. This may pave the way to further improved patient outcomes; however, further randomized clinical studies will be needed for a more definitive answer.
Since the discovery of epoxy in 1909 by Prileschajew [1], epoxy has become an important part of our daily life and integral to numerous industrial sectors. Epoxy is a plastic that has an epoxy ring, which consists of two carbon atoms that are bonded to a common oxygen atom. Epoxy resins are a class of reactive prepolymers and polymers that contain epoxide groups, which are cured using a wide variety of curing agents (i.e., hardener). Epoxy is one of the most important thermosetting polymers and has wide applications in different areas. The products’ properties largely depend on the structure of the epoxy resins and curing agents used. The excellent mechanical properties, high adhesiveness to many substrates, low shrinkage after curing, and good heat and chemical resistances make epoxy resins remarkably useful across a wide range of fields, where they act as reinforced materials, adhesives, coatings, etc. [2, 3, 4, 5].
Epoxy has been widely used as polymer matrix for composite applications. The properties of composites can be customized by adding functional fibers to endow the functionalities on the composites. For example, the fiber-reinforced epoxy composites have significantly improved mechanical properties. Song et al. [6] developed carbon fiber/epoxy composite laminates with carbon nitride, and their tensile strength and Young’s modulus reached 67 MPa and 58 GPa, respectively. Huang et al. [7] developed continuous bamboo fiber reinforced epoxy composites (i.e., long bamboo fiber as reinforcement rather than chopped fibers through a resin transfer molding process and achieved improved mechanical strain. Epoxy based composites not only have enhanced mechanical properties, they can also feature unique properties, such as electromagnetic interference shielding properties [8], self-healing [9], heat resistance [10], and others [3, 4].
Despite serving as a polymer matrix, epoxy, as a reactive molecule, can be used as fillers (or modifiers) to facilitate reinforce polymer composites. Fillers are typically added to polymers to modify their characteristics and/or reduce their price [11, 12, 13]. For instance, Zhao et al. applied epoxy to functionalize pine fibers that were used to reinforce the polylactic acid (PLA) [11]. Their results suggest that the epoxy modification is beneficial to improve the tensile strengths and Young’s moduli of the composites compared to that of neat PLA owing to the improved fiber/matrix interfacial adhesion. One reason is that the epoxy exhibits high adhesiveness and compatibilization effect. In another study conducted by Sujaritjun et al. [12], epoxidized polybutadiene treated bamboo fibers were used to reinforce PLA and achieved a 10% increase in the tensile strength. Similarly, Kyutoku et al. [13] utilized cellulose fibers coated with epoxy-based agents to reinforce PLA and found that the epoxy treatment improved the interfacial adhesion between cellulose fibers and PLA. Compared with other non-reactive surface functionalization of the nanofiber [14], the high reactivity of the epoxy group in the epoxy modified fibers is beneficial for improving the interfacial interactions between fibers and matrix, and thus can effectively reinforce polymers.
The cured epoxy resins are brittle due to the high degree of cross-linking, which weakens epoxy’s impact strength and other relevant properties [3, 15]. Therefore, chemical modification of epoxy monomers is necessary to improve their flexibility and toughness as well as other properties [16]. Many efforts have been devoted to addressing these challenges through introducing flexible polymers, inorganic solid particles, and elastomers [17, 18, 19]. Despite the brittleness, epoxies also have poor thermal and electrical conductivity [20]. To solve these challenges and improve the properties of the epoxy-based materials, different thermal conductive and electrical conductive materials (fibers), such as carbon nanotubes, graphene, carbon fiber, and others, were added [21]. However, the poor interfacial interaction between the fiber and epoxy led to low interfacial strength and impact toughness. Considerable efforts have been made to solve this issue [6, 7]. Additionally, bio-based epoxy [22] and epoxy-based vitrimer [23] also become new hot topics in this field driven by the desire for sustainability and recyclability [24] of composite materials.
Given the importance of the epoxy-based composites, in this chapter, the recent development of epoxies in polymer composites are summarized based on their roles. The basics of epoxy, such as structure, curing agents, and curing process, are discussed. The role of the epoxy compounds in the composites is discussed from the filler and polymer matrix aspects. Finally, the challenges and future opportunities in the epoxy-based composites are summarized.
Epoxy resin is often regarded as the most valuable polymer. It is widely utilized in numerous modern industries including aerospace [25], electrical encapsulation [26], chemical engineering [27], civil engineering [28], food industry [29], etc. Epoxy resins are part of the family of monomeric or oligomeric materials with excellent electrical insulation properties and extraordinary resistance to corrosion [30]. Epoxy resin has a group of reactive polymers, which contain epoxy or oxirane groups, as presented in Figure 1. According to their structure, characteristic, and functionality, there are three major types of epoxy resins: (i) cycloaliphatic, (ii) epoxidized, and (iii) glycated epoxy resins [31].
Epoxy or oxirane group.
The first two types of resins (cycloaliphatic and epoxidized) are synthesized directly via the corresponding olefin oxidation. Glycidated resins are prepared by glycidation of bisphenol A with epichlorhydrin. Generally, cycloaliphatic epoxy resins provide excellent ultraviolet (UV) stability and electrical properties, as well as good thermal stability due to their fully saturated structure. This feature makes them suitable for structural components under high-temperature situations. Furthermore, these resins are easy to obtain owing to their low viscosities and can be cured at low temperatures. This result is likely because these resins have simple structures, and the low viscosity leads to easy curing. However, they have a short pot life (useable life: the length of time that a system retains a viscosity low enough to be applied), as moisture and other factors easily affect the uncured resins. Bisphenol epoxy resin is a type of commercial resin, commonly composed of a mixture of oligomers. It has a wide variety of viscosities and low molecular weights, resulting in high-performance phenoxy lacquer resins [31].
Epoxy resins are utilized in various applications due to their outstanding properties and versatile nature [25, 29, 31]. Epoxy resins can form into thermoset or photosensitive resins, which are determined by reaction conditions and curing agents [32, 33]. Epoxy-based parts are usually manufactured in the desired shape by typical technologies including but not limited to resin infusion [34], injection molding [35], resin transfer molding [36], and autoclave [37]. Nevertheless, the above processed technologies cause several bottlenecks in terms of slow production, difficulties in producing complex geometries, labor-intensiveness, and high cost of the process, particularly considering thermal energy [31].
One significant characteristic of epoxy resins is that the curing process proceeds through a step-growth reaction without the generation of volatile byproducts. Subsequently, the process produces structures free from voids and bubbles. Therefore, the tailoring of cross-linkers and modifiers are critical in the steady growth rate of epoxy resins considering their further functionality. Because of the poor toughness, researchers explored and developed several strategies to improve the toughness of epoxy resins: (i) change in the chemical structure to make them more flexible [38], (ii) increase in the molecular weight [39], (iii) decrease in the cross-linking density [40], (iv) addition of a tougher phase, and (v) addition of fibers [29].
The desired properties of epoxy resins are generally determined by combining an epoxy resin and a curing agent. Curing agents can be catalysts usually drawn from amines, Lewis acids, or hardeners. Hardeners, identified as curing or cross-linking agents, can break the C-O-C ring at the ends of an epoxy molecule and attach themselves to the molecules to convert the resin into a thermoset network structure. Different curing agents can create composites with different properties because the curing agents have different functional sites that lead to different chemical reactions. A specific hardener should be selected based on processing conditions (viscosity, pot life, mixing ratio, and temperature) and the desired properties of the product (strength, chemical and thermal resistance, toughness, and flexibility). The most common hardeners for epoxy resins are amine types: (i) aliphatic, (ii) aromatic, and (iii) cycloaliphatic. The type, amount, functionality of the hardener, as well as the curing conditions (temperature and curing time), affect the properties of hardened epoxy resins. For example, difunctional epoxy resins are prepolymers with an epoxy group at each end of a molecule. The diglycidyl ether of bisphenol F (DGEBF) has similar molecular structures: the two methyl groups attached to the carbon between the benzene groups in the former are replaced with H atoms in the latter. F-type epoxies have lower viscosity than A-type epoxies. For this reason, A and F types are often mixed to lower the viscosity of a mixture, thus preventing the crystallization of the polymers [41].
Ozkul et al. [41] employed three different epoxy resins, diglycidyl ether of bisphenol A, diglycidyl ether of bisphenol F (DGEBF), and a mixture of the two; six amine type hardeners, four of which are aliphatic and the others are cycloaliphatic; and three glycidyl-ether based reactive diluents to study their effects towards the hardened state properties of epoxy mortars. Three epoxy resins and three types of glycidyl ether-based reactive diluents were used together in epoxy mortars. Six different amine-based hardeners, four aliphatic and two cycloaliphatic, were used in the mixtures. A hardener with a higher functionality (reactive point) led to mortars with higher strength.
Epoxy resins are in liquid form and the curing agent solidifies during the fabrication. During curing, the chemical reaction of the epoxide groups in the epoxy resin is initiated by a curing agent through a step-growth reaction, then form a 3D highly cross-linked network. Curing process conditions impact the properties of the cured resins. For example, the amount of curing agents influences the strength of the cured resin film and the formation time. There are three main methods of curing: (i) room-temperature curing, (ii) thermal curing, and (iii) photocuring [31].
Room temperature curing agents are used to cure epoxy resins at room temperature. These include aliphatic polyamines, low-molecular-weight polyamides, alicyclic polyamines, and modified aromatic amines. This curing system is preferred for higher flexibility, impact resistance, and electrical and thermal shock resistance [31]. The final structure of the cured resin highly depends on the employed temperature.
High temperature curing agents, for example, acid anhydrides, resol resins, aromatic polyamines, dicyandiamides, and hydrazides, are used to cure epoxy resins at elevated temperatures. Generally, high temperature curing is carried out in two stages: (i) precuring stage (gel-status) at a low temperature and (ii) postcuring stage (solid-status) at a high temperature. Epoxy components fabricated at higher temperatures exhibit higher tensile strength, heat resistance, and chemical resistance [31].
Photocuring systems significantly decrease the epoxy curing process time from hours to minutes and save the cost of energy compared to autoclave thermal curing. A wide range of radiation curing wavelengths, such as infrared light, UV light, X-rays, and electron beam irradiations, can be used to cure photosensitive epoxy resins employing photoinitiators. Photocuring is a relatively controllable and consistent process as compared to other curing processes [31].
Two-stage curing systems that combine photocuring and thermal curing enable the use of epoxy resins in additive manufacturing. Traditionally, epoxy resin and its composites are manufactured by curing at high temperatures for several hours. This condition makes epoxy resin impossible to use in additive manufacturing because, curing layer by layer is essential during fabrication. To solve this issue in additive manufacturing the common practice is to use photosensitive epoxy resin. However, this cured resin has poor mechanical properties, low curing rate, and high cost due to photoinitiators. Moreover, it does not meet the need for mechanical parts required in some specified industries. Direct-ink writing is a possible approach to use epoxy or other thermoset resins where the ink can be designed to be viscoelastic with the incorporation of a fiber [31].
Kuang et al. [42] demonstrates additive manufacturing of an epoxy resin using digital light processing. The hybrid ink is prepared by blending a thermally curable resin and a photocurable resin and cures in two stages. During manufacturing, the epoxy resin is exposed to UV-LED light with a wavelength of 385 nm (first-stage curing) to create the designed shape and then cured at 100°C for 2 h and another 2 h at 160°C (second-stage curing). The hybrid ink presents low volume shrinkage, desired mechanical properties and high resolution, enabling use in engineering applications. Griffini et al. [43] customizes a hybrid ink of thermal and photocurable epoxy resins to investigate the possibility of the fabrication of carbon fiber-reinforced composite structures. Carbon fibers with a diameter of 7.2 μm and length of 100–150 μm are added into the ink to develop an increased weight concentration. When the hybrid ink is extruded from the syringe, light from two UV-A torches with a wavelength of 405 nm irradiates the hybrid ink to solidify its shape in the first-stage curing. Then, the printed sample is cured at 220°C for 20 min in a ventilated oven for the second-stage curing. The weight ratio between thermal and photocurable components strongly influenced the printing characteristics. Carbon fibers also affected the efficiency of UV-curing.
Epoxy can be used as a non-matrix component (i.e., filler or minor component) in composites and is usually applied at the fiber and polymer matrix interface. Epoxy can be used to functionalize the surface of fibers with epoxy groups. Thus, the surface of the fibers can be activated to react with other components in the composites. Cheng et al. [44] uses a two-step method to epoxidize the surface of poly-p-phenylene-benzimidazole-terephthalamide (PBIA) fibers with epoxy groups. The PBIA fibers were first fluorinated and grafted with Si-OH groups. The Si-OH groups were then added with 3-glycidoxypropylthrimethoxysilane (GPTMS) for epoxidation. The modified fibers were then incorporated in an epoxy matrix with respect to surface energy and pull-out strength, where both the two properties were improved. The surface energy increased from 13 to 17 mN/m, while the pull-out strength improved from 0.45 to 0.63 N/(tex·mm). Fei et al. [45] used the epoxy group as an activate site to graft polymer chains for functional composites. The bacterial cellulose was first epoxidized with epoxy chloropropane (ECP) at the hydroxyl groups on cellulose. Aniline was then added and grew from the epoxy group to polyaniline (PANI), providing electrical conductivity in the final cellulose-based flexible paper. The electrical conductivity can reach 1.1 S/cm at proper ECP concentrations and can be further improved up to 1.4 S/cm by introducing polyacrylamide via enhancing the interaction between PANI and the fibers.
Another epoxidation was done by Cao et al. [46] on tunicate cellulose nanocrystals (T-CNC), which exhibit a higher aspect ratio than cotton CNC. GPTMS was used to introduce epoxy groups on the surface of T-CNC first. The modified fibers were then blended with carboxylate styrene−butadiene rubber. The covalent bonding between epoxy and carboxyl groups was improved. The tensile strength, modulus, and toughness were improved with more modified T-CNC added. In addition, the resultant rubber could be reprocessed, attributed to the transesterification of the ester bonding formed by epoxy and carboxyl groups. This modification enabled the composites to maintain their original tensile strength even after reprocessing three times. In these methods, epoxy significantly altered the surface chemistry and the interfacial adhesion. However, one issue was that the epoxidation process usually involved highly activate reagents, like ECP, which may bring an uncontrollable by-reaction that will affect the properties of the final product [45].
Epoxy are utilized to adjust the properties of composites. A single domain or phase with an epoxy group is introduced into composites. The properties of the composites change depending on the inherent properties of the epoxy group. Epoxy can also react with other components to bring new bonding. For example, Immonen et al. [47] used epoxidized linseed oil (ELO) as an epoxy phase in a PLA-based composites with bleached softwood kraft pulp (BSKP) as the fiber. At certain concentrations of ELO, the trinary composites exhibited improved tensile strength, modulus, elongation at break, and impact strength compared with neat PLA and BSKP/PLA composites. This result inferred that ELO could react with both PLA and BKSP, thus enhancing the interfacial adhesion between PLA and BSKP. A similar idea was applied by using tannic acid-crosslinked epoxidized soybean oil (TA-ESO) in bamboo fiber (BF)/PLA composites as reported in Liu et al.’s work [48]. In their composite system, BF was the reinforcing fiber that could improve tensile strength and modulus as more incorporated, while decreasing the elongation at break. TA-ESO was introduced by solution-spray onto the BFs and then dried to modify the surface of BF for better interaction with the PLA matrix. TA-ESO was expected to act as a bridge between the two phases to enhance the interfacial adhesion. At a low concentration (0.5 wt%) of TA-ESO, the epoxy phase mainly acted as a compatibilizer between PLA and BF since hydroxyl groups on both PLA and BF could react with epoxy group on EOS, contributing to the force transfer from PLA to BF to improve the tensile strength. As TA-EOS content increased, excessive TA-EOS could be presented as a single phase, which acted as a toughing domain in PLA composites and a compatibilization effect on the interface. However, TA-EOS at higher concentration resulted in poor tensile performance and impact strength due to the large domain area. Nevertheless, TA-EOS could be used to balance the tensile strength and toughness by varying the feeding ratio compared to BF and PLA matrix.
Similarly, Zhao et al. [11] impregnated an epoxy solution to pine fibers to fill and penetrate the voids and hollow channels in the pine fibers. By mixing curing agent (Dicyandiamide) and epoxy resin (Poly(bisphenol A-co-epichlorohydrin), glycidyl end-capped), part of the epoxy cured during the drying process, modifying the surface chemistry. This method benefited the tensile strength, where the tensile strength and Young’s modulus improved by 20% and 82%, respectively, at 1 wt% loading of the epoxy system. The better interfacial adhesion between PLA and pine fibers came from the compatibilization effect of the epoxy. Epoxy curing during the hot pressing for final composites may bridge PLA and pine fibers by a covalent bond. The epoxy enhanced the interaction between polymer matrix and pine fibers increasing the tensile performance. Through this approach, the preparation of the composites was conducted without complex chemical reactions. However, the property of the final products depended on the inherent property and concentration of the epoxy-included phase which should be carefully selected [48].
Epoxies are extensively used as the polymer matrix of composites for their salient features of high specific strength, good dimensional stability, and excellent dielectric properties [1, 30, 49]. Due to the high cross-link density formed during curing, neat epoxy resins are intrinsically brittle and have low fracture toughness, which can limit their application in some specified fields. Moreover, epoxy resins are relatively expensive in comparison with other commonly used thermosetting resins, such as unsaturated polyester and vinyl ester resins. Adding fibers into epoxies could enhance the thermal and durability properties [50]. However, the addition of fibers can impart adverse influence on composites’ physical and mechanical properties alongside the reinforcement on other properties. Therefore, attention needs to be paid to optimizing and balancing different properties and costs when designing composites for specific applications. Table 1 summarizes the general types and fabrication techniques of epoxy-based composites. Some applications and recent developments of high-performance and cost-effective epoxy composites are briefly reviewed herein.
Type | Fiber | Fabrication techniques |
---|---|---|
Conventional composites |
|
|
Nanocomposites |
|
|
Fiber reinforcement is a common strategy for preparing epoxy composites and is widely adopted in the industry [50, 54]. Synthetic fibers, such as glass, carbon, and aramid, offer load bearing capability and enhancement of mechanical properties, while the epoxy functions as a binder that forms an overall solid shape and transfers the stress uniformly onto the fibers inside the matrix. Particularly, epoxies exhibit a low viscosity before curing that helps with fiber wetting and minimizing air voids, aiding in the composite strength. Meanwhile, the low viscosity provides a unique processing versatility such that various options of fabrication techniques can be applied for the industrial manufacture of epoxy composites (see Table 1). These characteristics, alongside outstanding chemical and mechanical properties after being cured, let fiber-reinforced epoxies find a broad range of commercial applications in structural materials, commercial and sporting goods, and civil infrastructures, as well as diverse lightweight engineering applications in automotive, marine, aerospace, and wind turbine construction, for which the high strength-to-weight ratio allows for substantial fuel and energy savings [50].
Glass fibers are readily available and relatively cheap on the commodity market, making them the most used fibers in the composite industry. Glass fibers have high tensile strength and excellent insulating properties [54, 55]. Glass fiber-reinforced epoxy composites are often fabricated by distributing discontinuous or continuous glass fibers, randomly oriented, inside the epoxy matrices. By combining the complementary features of glass fiber and epoxy, the ensuing composite provides a superior material for the replacement of heavier metal and ceramic parts in structural and insulation applications. Being another commonly used reinforcement fiber, carbon fiber is stronger, lighter, and more expensive than glass fiber (see Table 2). Epoxy adheres well to carbon fiber. The manufacturing of carbon fiber composites usually involves the epoxy impregnation of carbon fabric [34, 36]. The strength of laminated composites depends on the weave pattern, orientation, and weight fraction of the carbon fabric, which is generally stronger than that of the glass fiber reinforcement, leading to more advanced applications.
Material | Bulk density (g/cm3) | Tensile strength (MPa) | Young’s modulus (GPa) | Toughness (mJ/mm3) |
---|---|---|---|---|
Glass | 2.5 | 1048 | 62 | 21 |
Carbon | 1.8 | 2302 | 168 | 46 |
Aramid | 1.4 | 2273 | 47 | 92 |
Typical properties of commonly used reinforcement fibers [54].
In addition to synthetic fibers, natural fibers received considerable attention in past decades in view of environmental concerns [56, 57, 58, 59]. Natural fibers are mostly sourced from plants or animals and are biodegradable and renewable [60, 61]. Their replacement of synthetic fibers in composite applications can reduce carbon footprint, improve recyclability, and enhance environmental sustainability. Studies have examined epoxy composites reinforced by natural fibers, such as kenaf, coir, sisal, banana, jute, bamboo, cotton, bagasse, flax, ramie, and luffa. These studies suggest these natural fibers reinforce epoxy’s physical and mechanical properties and are suitable for low-load applications [62, 63]. Despite growing interest, bio-based materials have seen relatively slow market growth in the consumption of natural fibers [64]. This result provides an opportunity for fostering applications of natural fiber reinforced epoxy composites. However, the development of fiber processing and chemical treatment technologies is needed to improve the performance of epoxy composites with natural fibers.
Given the increasing demand of high-performance materials in lightweight construction and renewable energy generation, significant research efforts are devoted to improving the mechanical properties of fiber-reinforced epoxies and extending their functional applications. Poor damage tolerance and fire resistance are significant obstacles that limit the applications of conventional epoxy-based composites [53]. Notably, their anisotropic nature and weak out-of-plane mechanical properties induce low impact resistance for composites with aligned reinforcement fibers. Meanwhile, the debonding between fiber and matrix under transverse and compression loading can cause delamination that significantly deteriorates the mechanical performances and hence, reduces the service life of composite materials. In addition, the cured epoxy matrix decomposes when exposed to high temperatures (300–400 °C), releasing heat, smoke, and toxic volatiles and byproducts [65]. Managing the fire risk and subsequent environmental hazard is thus crucial for broadening the application range of epoxy composites.
Strategies for composite property improvement focus on developing the matrix, fiber, and the interface of composite materials [66]. Toughening of the epoxy matrix is the most effective way to improve the composite impact strength for structural applications [17, 67]. Standard methodologies for the epoxy toughening include the chemical modification of the epoxy and the integration of toughening agents. In the former scenario, reducing the cross-link density (by increasing the segment length between crosslinks), increasing the molecular weight of epoxy monomers, or modifying the rigid backbone structure to be flexible increases the impact toughness. However, these changes impose significant reductions in other properties, e.g., modulus, tensile and flexural strength, as well as decrease the glass transition temperature that affects the thermal stability. Considering this synergistic effect, the industrial formulations of epoxies often reflect the tradeoff of balancing different properties for end applications. In this regard, blending toughening agents (typically, 5–20 wt%) becomes a more facile approach [16, 17].
Typical toughening agents include liquid rubbers, thermoplastics, hyperbranched polymers, block copolymers, and inorganic nanoparticles, among which the liquid rubber is a more common choice for industrial applications as it is more economical and easier to process [68]. Several types of reactive liquid rubbers, namely, carboxyl-terminated poly (butadiene-co-acrylonitrile), amine-terminated poly (butadiene-co-acrylonitrile), and hydroxyl terminated polybutadiene, have been developed to increase the epoxy toughness [27, 69]. However, these polybutadiene derivatives have unsaturated sites along the backbone that are susceptible to degradation in a high-temperature and oxidative environment. To overcome this deficiency, saturated liquid rubbers, such as polyacrylates, polysiloxane, and polyurethane, are introduced as alternatives that offer better oxidative stability [70]. The liquid rubber toughening is found to be effective for difunctional epoxy resins but ineffective for tri and tetrafunctional epoxy resins that have a higher degree of cross-linking, suggesting that the toughening of the matrix increases with increasing the inherent ductility of the epoxy [53, 69].
Thermoplastics constitute another significant type of toughening agents, which enhance the toughness for both difunctional and multifunctional epoxy resins without scarifying other desirable mechanical properties (as is the case for the rubber toughening). Since the early 1980s, several thermoplastics have been applied, including polysulfone, poly (ether imide), poly (ether sulfone), and poly (phenylene oxide) [70, 71]. It is well recognized that the toughening effect of thermoplastic depends on its phase structure inside the matrix. Notably, a co-continuous morphology at a high thermoplastic concentration, in contrast to the discrete morphology, can induce a sharper increase in the fracture toughness with increasing the thermoplastic content [71]. Nevertheless, the manipulation of phase structures (through varying the composition and curing condition) and the optimization of formulations for different applications require additional engineering.
Alongside the development in conventional toughening strategies, block copolymers and nanoparticles emerge as promising additives for epoxy toughening, which gain increasing interest in recent years [17, 19, 72]. Specifically, block copolymers can undergo microphase separation under the thermodynamic driving force. This result imparts a fine-tuning of phase structures at the nanoscale that affects the properties of nanodomains inside the matrix, resulting in stronger enhancement effects compared to conventional agents of larger sizes. Similarly, nanoparticles significantly enlarge the interface between fiber and matrix upon good dispersion inside epoxy. A small amount of nanoparticles can dramatically improve the matrix properties. Moreover, the incorporation of different types of nanoparticles (Table 1), and surface modifications [4], lead to epoxy nanocomposites with enhanced electrical conductivity, thermal conductivity, magnetic, flame retardant, and radiation resistant properties [51, 73], expanding their utility in functional applications.
Overall, considering that different types of agents are associated with different toughening mechanisms (functioning at different length scales), a hybridization strategy can be adopted to prepare fiber-reinforced hybrid epoxy composites that enable synergistic toughening [67, 72, 74, 75]. Given the large degree of freedom of the components, the development of multiscale computer simulations [76, 77], machine learning, and experimental studies are needed to expedite the rational design of advanced epoxy composites.
Epoxy has high adhesiveness and is widely used in industry. However, no systematic study has been performed on using epoxy as a filler or polymer matrix for composite applications. This chapter has systematically reviewed recent research and advances on epoxy-based composites. Discussion includes analysis of the epoxy type, epoxy function, curing agent, curing process, and performance of epoxy-based composites.
Epoxy resin has a group of reactive polymers that contain epoxy or oxirane groups. There are three major types of epoxy resins: cycloaliphatic, epoxidized, and glycated epoxy resins. Epoxy-based materials are manufactured into the desired shape by injection molding, resin transfer molding, or resin infusion. The desired properties of epoxy resins are generally determined by the combination of an epoxy resin and a curing agent. Three main methods of curing are room-temperature curing, thermal curing, and photocuring. During curing, the chemical reaction of the epoxide groups in the epoxy resin is initiated by a curing agent to form a highly cross-linked network.
As a filler, there are two common approaches to utilize epoxy. One is to functionalize the fiber’s surface with epoxy groups so that the fiber’s surface can be activated to react with other components in the composites. The other one is to incorporate epoxy as a single domain or phase in the composites with epoxy groups. However, the composites’ performance will be influenced by the inherent property of the epoxy and the concentration of the epoxy-included phase.
Epoxy is used as a polymer matrix because of its high specific strength, excellent adhesion, and good dimensional stability. Adding fibers into epoxies improves the thermal and durability properties while reducing the cost for composite applications. However, the addition of fibers can adversely influence the mechanical and physical properties of composites. Toughening the epoxy is an effective way to improve the composite’s impact strength for structural applications. Typical toughening agents include thermoplastics, liquid rubbers, block copolymers, and nanoparticles. Liquid rubbers are a more common choice for industrial applications as they are more economical and easier to process.
Challenges and future directions:
As a filler, the epoxy’s inherent property affects the composites’ performance. In addition, the epoxidation process typically involves highly active reagents that can cause uncontrollable side effects that influence the properties of the composites. The selection of appropriate epoxies with a high functionality is a challenge. The epoxy solution concentration, drying process, and advanced epoxy with outstanding mechanical properties can be investigated in the future.
As a polymer matrix, the poor interfacial interaction between the epoxy matrix and fibers is a key challenge. Toughening of the epoxy is an effective pathway to address this challenge. The manipulation of phase structures and the optimization of formulations for different applications require additional engineering.
Bio-based epoxy can be developed towards the sustainability and recyclability of the composites. Environmentally friendly and economically viable bio-based epoxies are needed.
The authors acknowledge the support from the US Department of Energy (DOE) FY 2021 BETO Project under Contract 1.2.1.9 with UT-Battelle LLC, and the US DOE, Office of Energy Efficiency and Renewable Energy, Advanced Manufacturing Office, under CPS Agreement 35714. This book chapter was authored in part by UT-Battelle LLC under contract DE-AC05-00OR22725 with DOE. The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this book chapter, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).
The authors declare no conflict of interest.
BF | Bamboo fiber |
BSKP | Bleached softwood kraft pulp |
DGEBF | Diglycidyl ether of bisphenol F |
ECP | Epoxy chloropropane |
ELO | Epoxidized linseed oil |
GPTMS | 3-glycidoxypropylthrimethoxysilane |
PANI | Polyaniline |
PBIA | Poly-p-phenylene-benzimidazole-terephthalamide |
PLA | Polylactic acid |
T-CNC | Tunicate cellulose nanocrystals |
TA-ESO | Tannic acid-crosslinked epoxidized soybean oil |
UV | Ultraviolet |
Authors are listed below with their open access chapters linked via author name:
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\\n\\nYiqi Luo 2016-18
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\\n\\nAndrea Natale 2017, 2018
\\n\\nAlberto Mantovani 2014-18
\\n\\nMarjan Mernik 2017, 2018
\\n\\nSandra Orchard 2014, 2016-18
\\n\\nMohamed Oukka 2016-18
\\n\\nBiswajeet Pradhan 2016-18
\\n\\nDirk Raes 2017, 2018
\\n\\nUlrike Ravens-Sieberer 2016-18
\\n\\nYexiang Tong 2017, 2018
\\n\\nJim Van Os 2015-18
\\n\\nLong Wang 2017, 2018
\\n\\nFei Wei 2016-18
\\n\\nIoannis Xenarios 2017, 2018
\\n\\nQi Xie 2016-18
\\n\\nXin-She Yang 2017, 2018
\\n\\nYulong Yin 2015, 2017, 2018
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\n\nAbdul Latif Ahmad 2016-18
\n\nKhalil Amine 2017, 2018
\n\nEwan Birney 2015-18
\n\nFrede Blaabjerg 2015-18
\n\nGang Chen 2016-18
\n\nJunhong Chen 2017, 2018
\n\nZhigang Chen 2016, 2018
\n\nMyung-Haing Cho 2016, 2018
\n\nMark Connors 2015-18
\n\nCyrus Cooper 2017, 2018
\n\nLiming Dai 2015-18
\n\nWeihua Deng 2017, 2018
\n\nVincenzo Fogliano 2017, 2018
\n\nRon de Graaf 2014-18
\n\nHarald Haas 2017, 2018
\n\nFrancisco Herrera 2017, 2018
\n\nJaakko Kangasjärvi 2015-18
\n\nHamid Reza Karimi 2016-18
\n\nJunji Kido 2014-18
\n\nJose Luiszamorano 2015-18
\n\nYiqi Luo 2016-18
\n\nJoachim Maier 2014-18
\n\nAndrea Natale 2017, 2018
\n\nAlberto Mantovani 2014-18
\n\nMarjan Mernik 2017, 2018
\n\nSandra Orchard 2014, 2016-18
\n\nMohamed Oukka 2016-18
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Medicine",slug:"cardiology-and-cardiovascular-medicine"},numberOfBooks:6,numberOfSeries:0,numberOfAuthorsAndEditors:154,numberOfWosCitations:62,numberOfCrossrefCitations:52,numberOfDimensionsCitations:104,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"984",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"9060",title:"The Current Perspectives on Coronary Artery Bypass Grafting",subtitle:null,isOpenForSubmission:!1,hash:"cedc3547eae8f66f9440cc35216d7963",slug:"the-current-perspectives-on-coronary-artery-bypass-grafting",bookSignature:"Takashi Murashita",coverURL:"https://cdn.intechopen.com/books/images_new/9060.jpg",editedByType:"Edited by",editors:[{id:"192448",title:"Dr.",name:"Takashi",middleName:null,surname:"Murashita",slug:"takashi-murashita",fullName:"Takashi Murashita"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8819",title:"Cardiac Surgery Procedures",subtitle:null,isOpenForSubmission:!1,hash:"3d84cc6e6750d835e4b86578dfdbbdd9",slug:"cardiac-surgery-procedures",bookSignature:"Andrea Montalto, Antonio Loforte and Cristiano Amarelli",coverURL:"https://cdn.intechopen.com/books/images_new/8819.jpg",editedByType:"Edited by",editors:[{id:"222866",title:"Dr.",name:"Andrea",middleName:null,surname:"Montalto",slug:"andrea-montalto",fullName:"Andrea Montalto"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8218",title:"Aortic Stenosis",subtitle:"Current Perspectives",isOpenForSubmission:!1,hash:"d9a81a576f7026e76fa6d29c27b308a6",slug:"aortic-stenosis-current-perspectives",bookSignature:"Peter Magnusson",coverURL:"https://cdn.intechopen.com/books/images_new/8218.jpg",editedByType:"Edited 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Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/6556.jpg",editedByType:"Edited by",editors:[{id:"64343",title:"Dr.",name:"Michael S.",middleName:null,surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3542",title:"Artery Bypass",subtitle:null,isOpenForSubmission:!1,hash:"6b48ec67e1291ca98f3aded6a9af92ca",slug:"artery-bypass",bookSignature:"Wilbert S. Aronow",coverURL:"https://cdn.intechopen.com/books/images_new/3542.jpg",editedByType:"Edited by",editors:[{id:"164597",title:"Dr.",name:"Wilbert S.",middleName:null,surname:"Aronow",slug:"wilbert-s.-aronow",fullName:"Wilbert S. Aronow"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:6,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"43500",doi:"10.5772/54723",title:"Pharmacology of Arterial Grafts for Coronary Artery Bypass Surgery",slug:"pharmacology-of-arterial-grafts-for-coronary-artery-bypass-surgery",totalDownloads:2976,totalCrossrefCites:9,totalDimensionsCites:19,abstract:null,book:{id:"3542",slug:"artery-bypass",title:"Artery Bypass",fullTitle:"Artery Bypass"},signatures:"Oguzhan Yildiz, Melik Seyrek and Husamettin Gul",authors:[{id:"164299",title:"Prof.",name:"Oguzhan",middleName:null,surname:"Yıldız",slug:"oguzhan-yildiz",fullName:"Oguzhan Yıldız"},{id:"164968",title:"Dr.",name:"Melik",middleName:null,surname:"Seyrek",slug:"melik-seyrek",fullName:"Melik Seyrek"},{id:"164969",title:"Dr.",name:"Husamettin",middleName:null,surname:"Gul",slug:"husamettin-gul",fullName:"Husamettin Gul"}]},{id:"43514",doi:"10.5772/54418",title:"The Role of The Angiosome Model in Treatment of Critical Limb Ischemia",slug:"the-role-of-the-angiosome-model-in-treatment-of-critical-limb-ischemia",totalDownloads:3760,totalCrossrefCites:5,totalDimensionsCites:11,abstract:null,book:{id:"3542",slug:"artery-bypass",title:"Artery Bypass",fullTitle:"Artery Bypass"},signatures:"Kim Houlind and Johnny Christensen",authors:[{id:"165363",title:"Associate Prof.",name:"Kim",middleName:null,surname:"Houlind",slug:"kim-houlind",fullName:"Kim Houlind"},{id:"167383",title:"Dr.",name:"Johnny",middleName:null,surname:"Christensen",slug:"johnny-christensen",fullName:"Johnny Christensen"}]},{id:"43476",doi:"10.5772/54509",title:"Impact of Ischemia on Cellular Metabolism",slug:"impact-of-ischemia-on-cellular-metabolism",totalDownloads:2729,totalCrossrefCites:5,totalDimensionsCites:9,abstract:null,book:{id:"3542",slug:"artery-bypass",title:"Artery Bypass",fullTitle:"Artery Bypass"},signatures:"Maximilien Gourdin and Philippe Dubois",authors:[{id:"164978",title:"Prof.",name:"Philippe",middleName:"E",surname:"Dubois",slug:"philippe-dubois",fullName:"Philippe Dubois"},{id:"164982",title:"Dr.",name:"Maximilien",middleName:null,surname:"Gourdin",slug:"maximilien-gourdin",fullName:"Maximilien Gourdin"}]},{id:"61397",doi:"10.5772/intechopen.76844",title:"The Ethics in Repeat Heart Valve Replacement Surgery",slug:"the-ethics-in-repeat-heart-valve-replacement-surgery",totalDownloads:1154,totalCrossrefCites:3,totalDimensionsCites:6,abstract:"The treatment of patients with intravenous drug use (IVDU) has evolved to include a wide range of medications, psychiatric rehabilitation, and surgical interventions, especially for life-threatening complications such as infective endocarditis (IE). These interventions remain at the discretion of physicians, particularly surgeons, whose treatment decisions are influenced by several medical factors, unfortunately not without bias. The stigma associated with substance use disorder is prevalent, which leads to significant biases, even in the healthcare system. This bias is heightened when IVDU patients require repeat valve replacement surgeries for IE due to continued drug use. Patients who receive a valve replacement and continue to use illicit drugs intravenously often return to their medical providers, months to a few years later, with a reinfection of their bioprosthetic valve; such patients require additional surgeries which are at the center of many ethical discussions due to high mortality rates, for many complex medical and social reasons, associated with continuous chemical dependency after surgical interventions. This chapter examines the ethics of repeat heart valve replacement surgery for patients who are struggling with addiction. Considerations of justice, the fiduciary therapeutic relationship, and guiding ethical principles justify medically beneficial repeat heart valve replacement surgeries for IVDU patient populations.",book:{id:"6556",slug:"advanced-concepts-in-endocarditis",title:"Advanced Concepts in Endocarditis",fullTitle:"Advanced Concepts in Endocarditis"},signatures:"Julie M. Aultman, Emanuela Peshel, Cyril Harfouche and Michael S.\nFirstenberg",authors:[{id:"64343",title:"Dr.",name:"Michael S.",middleName:null,surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"},{id:"227150",title:"Ms.",name:"Emanuela",middleName:null,surname:"Peshel",slug:"emanuela-peshel",fullName:"Emanuela Peshel"},{id:"229719",title:"Dr.",name:"Julie",middleName:"M.",surname:"Aultman",slug:"julie-aultman",fullName:"Julie Aultman"},{id:"232060",title:"Mr.",name:"Cyril",middleName:null,surname:"Harfouche",slug:"cyril-harfouche",fullName:"Cyril Harfouche"}]},{id:"43498",doi:"10.5772/54928",title:"Treatment of Coronary Artery Bypass Graft Failure",slug:"treatment-of-coronary-artery-bypass-graft-failure",totalDownloads:4781,totalCrossrefCites:3,totalDimensionsCites:5,abstract:null,book:{id:"3542",slug:"artery-bypass",title:"Artery Bypass",fullTitle:"Artery Bypass"},signatures:"M.A. Beijk and R.E. Harskamp",authors:[{id:"164896",title:"Dr.",name:"Marcel",middleName:"A.",surname:"Beijk",slug:"marcel-beijk",fullName:"Marcel Beijk"},{id:"165094",title:"Dr.",name:"Ralf",middleName:null,surname:"Harskamp",slug:"ralf-harskamp",fullName:"Ralf Harskamp"}]}],mostDownloadedChaptersLast30Days:[{id:"80213",title:"Evolution of Heart Transplantation Surgical Techniques",slug:"evolution-of-heart-transplantation-surgical-techniques",totalDownloads:222,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Organ transplantation has kindled the human imagination since the beginning of time. Prehistorically, transplantation appeared as mythological stories: from creatures with body parts from different species, the heart transplant between two Chinese soldiers by Pien Ch’iao, to the leg transplant by physician Saints Cosmas and Damian. By 19th century, the transplantation concept become possible by extensive contributions from scientists and clinicians whose works had taken generations. Although Alexis Carrel is known as the founding father of experimental organ transplantation, many legendary names had contributed to the experimental works of heart transplantation, including Guthrie, Mann, and Demikhov. The major contribution to experimental heart transplantation before the clinical era were made by a team lead by Richard Lower and Norman Shumway at Stanford University in the early 1960s. They played the vital role in developing experimental and clinical heart transplantation as it is known today. Using Shumway biatrial technique Christiaan Barnard started a new era of clinical heart transplantation, by performing the first in man human-to-human heart transplantation in 1967. The techniques of heart transplant have evolved since the first heart transplant. This chapter will summarize the techniques that have been used in clinical heart transplantation.",book:{id:"11236",slug:null,title:"Heart Transplantation - New Insights in Therapeutic Strategies",fullTitle:"Heart Transplantation - New Insights in Therapeutic Strategies"},signatures:"Samuel Jacob, Anthony N. Pham and Si M. Pham",authors:null},{id:"70032",title:"Coronary Artery Bypass Grafting: Surgical Anastomosis: Tips and Tricks",slug:"coronary-artery-bypass-grafting-surgical-anastomosis-tips-and-tricks",totalDownloads:1310,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"The definite feature of coronary artery disease is the focal narrowing in the vascular endothelium, and this leads to the decrease in the flow of blood to the myocardium. Atherosclerotic plaque is the main lesion. These patients can present with chest pain (angina or myocardial infarction) and need further workup noninvasively and invasively for the management. The main reasons for myocardial revascularization can be: (1) relief from symptoms of myocardial ischemia; (2) reduce the risks of future mortality; (3) to treat or prevent morbidities such as myocardial infarction, arrhythmias, or heart failure. Coronary artery bypass grafting (CABG) is the surgical technique of cardiac revascularization. In 1910, Dr. Alexis Carrel described a series of canine experiments in which he devised means to treat CAD by creating a “complementary circulation” for the diseased native coronary arteries. No clinical translation occurred at the time, but he was awarded the Nobel Prize in Medicine. Experimental refinements of coronary arterial revascularization, including the use of internal thoracic artery (ITA) grafts, were later reported by Murray and colleagues, Demikhov, and Goetz and colleagues in the 1950s and early 1960s. Dr. Rene Favaloro performed his first coronary bypass operation in May 1967 with an interposed saphenous vein graft (SVG) and shortly thereafter used aortocoronary bypasses sutured proximally to the ascending aorta. The stenosed segment is bypassed using an arterial or venous graft. Left internal thoracic artery is the most commonly used artery, and long saphenous vein is the most commonly used vein for the coronary artery grafting to reestablish the blood flow to the compromised myocardium. This can be performed with or without the help of cardiopulmonary bypass machine and also with or without arresting the heart. These techniques are called as on-pump beating or on-pump arrested and off-pump beating coronary artery bypass grafting surgery. Distal and proximal anastomoses are usually performed in an end-to-side manner, but in the case of doing sequential grafting, side-to-side anastomosis is also performed proximal to the end-to-side anastomosis. In this chapter we are going to discuss the coronary artery bypass grafting tips and tricks in details.",book:{id:"9060",slug:"the-current-perspectives-on-coronary-artery-bypass-grafting",title:"The Current Perspectives on Coronary Artery Bypass Grafting",fullTitle:"The Current Perspectives on Coronary Artery Bypass Grafting"},signatures:"Mohd. Shahbaaz Khan",authors:[{id:"278633",title:"Dr.",name:"Mohd. Shahbaaz",middleName:null,surname:"Khan",slug:"mohd.-shahbaaz-khan",fullName:"Mohd. Shahbaaz Khan"}]},{id:"65984",title:"Low Flow Low Gradient Severe Aortic Stenosis: Diagnosis and Treatment",slug:"low-flow-low-gradient-severe-aortic-stenosis-diagnosis-and-treatment",totalDownloads:2189,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Approximately 40% of patients with aortic stenosis (AS) show discordant Doppler-echocardiographic parameters with aortic valve area (AVA) <1 cm2 and/or index iAVA <0.6 cm2/m2 (consistent with severe AS) and the mean gradient (MG) <40 mmHg, consistent with mild/moderate AS. Accurate diagnosis of true severe low flow low gradient AS versus pseudo-severe aortic stenosis is important for prognosis and optimal timing for intervention. Doppler echocardiography using intravenous low dose dobutamine challenge is widely used for differentiating pseudo-severe from true severe aortic stenosis. However, relying on echocardiography alone may have limitations in accurate diagnosis. Reliable diagnosis using echocardiography is dependent on multiple factors like the angle of interrogation of the aortic jet, the assumption that the LVOT area is circular in cross section, optimal echo windows, the presence of underlying subclinical coronary artery disease prior to dobutamine challenge etc. In this chapter, we describe non-invasive and invasive strategies to assess the aortic valve using dobutamine stress. Direct measurement of gradients across the aortic valve while estimating the change in cardiac output and aortic valve area with increments of dobutamine infusion dose is complementary, safe and useful when conventional echocardiography techniques are inconclusive. Finally, the chapter describes effective strategies of treatment for low gradient severe aortic stenosis, including the role for diagnostic balloon valvuloplasty, in the era of transcatheter valve replacement (TAVR).",book:{id:"8218",slug:"aortic-stenosis-current-perspectives",title:"Aortic Stenosis",fullTitle:"Aortic Stenosis - Current Perspectives"},signatures:"Faeez Mohamad Ali, Vindhya Wilson and Rajesh Nair",authors:[{id:"280651",title:"Dr.",name:"Rajesh",middleName:null,surname:"Nair",slug:"rajesh-nair",fullName:"Rajesh Nair"},{id:"280829",title:"Dr.",name:"Faeez",middleName:null,surname:"Mohamad Ali",slug:"faeez-mohamad-ali",fullName:"Faeez Mohamad Ali"},{id:"290351",title:"Dr.",name:"Vindhya",middleName:null,surname:"Wilson",slug:"vindhya-wilson",fullName:"Vindhya Wilson"}]},{id:"59547",title:"Left Ventricular Assist Device Infections",slug:"left-ventricular-assist-device-infections",totalDownloads:1448,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Left ventricular assist device (LVAD) infections are important causes of morbidity and mortality in patients who receive these mechanical circulatory supports as a bridge to transplantation (BTT) or as destination therapy (DT) (for individuals who are not candidates for cardiac transplant). Infections are more common among persons who received pulsatile flow LVADs as opposed to newer continuous flow (CF) devices. Other risk factors for infection include obesity, renal failure, depression and immunosuppression. An LVAD infection increases the risk of infections in persons who undergo cardiac transplantation. Infections include percutaneous site, driveline, pump pocket and pump/cannula infections; sepsis, bacteremia, mediastinitis and endocarditis. Diagnosis is achieved by monitoring LVAD flow parameters and observing typical clinical and laboratory manifestations of infection. Imaging such as PET-CT or SPECT-CT imaging can be helpful to establish a diagnosis of pump pocket infection. Echocardiography may aid in detecting native valve endocarditis and thrombus associated with the LVAD. The most common pathogens include Staphylococcus, Corynebacterium, Enterococcus, Pseudomonas and Candida spp. Treatment requires targeted antimicrobials plus surgical debridement of infected tissue and device components. In cases of pump/cannula/LVAD endocarditis, especially if fungal pathogens or Mycobacterium chimaera are involved, LVAD removal/reimplantation vs. transplant is necessary, combined with extended antimicrobial therapy.",book:{id:"6556",slug:"advanced-concepts-in-endocarditis",title:"Advanced Concepts in Endocarditis",fullTitle:"Advanced Concepts in Endocarditis"},signatures:"Marion J. Skalweit",authors:[{id:"186717",title:"Associate Prof.",name:"Marion",middleName:null,surname:"Skalweit",slug:"marion-skalweit",fullName:"Marion Skalweit"}]},{id:"60658",title:"Humoral Rejection in Cardiac Transplantation: Management of Antibody-Mediated Rejection",slug:"humoral-rejection-in-cardiac-transplantation-management-of-antibody-mediated-rejection",totalDownloads:1072,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"After a successful heart transplantation, fundamental keys to achieve good results in the long term are to establish immunosuppressive therapy in the postoperative period in an appropriate manner and to ensure continuity of follow-ups. Despite the fact that these stages are maintained perfectly, patients may face one or more rejection episodes. T-cell-mediated acute cellular rejection of the cardiac allograft has well-established treatment algorithms, whereas antibody-mediated rejection (AMR) is challenging to diagnose, and its treatment varies between centers. Investigators reported that AMR is among the most important factors to improving long-term outcomes. Improved understanding of the roles of acute and chronic AMR has evolved in recent years following a major progress in the technical ability to detect and quantify recipient antihuman leukocyte antigen (HLA) antibody production. Recently, a study of the immunobiology of B cells and plasma cells that pertains to allograft rejection and tolerance has emerged. There are some questions regarding the classification of AMR, the diagnostic approaches, and the treatment strategies for managing. In this chapter, we are discuss the effector mechanisms that are used by antibodies to eliminate antigens and clinical experience about AMR and its treatment with a discussion about the latest articles.",book:{id:"6558",slug:"heart-transplantation",title:"Heart Transplantation",fullTitle:"Heart Transplantation"},signatures:"Umit Kervan, Dogan Emre Sert and Nesrin Turan",authors:[{id:"227772",title:"Prof.",name:"Umit",middleName:null,surname:"Kervan",slug:"umit-kervan",fullName:"Umit Kervan"},{id:"243592",title:"Dr.",name:"Dogan Emre",middleName:null,surname:"Sert",slug:"dogan-emre-sert",fullName:"Dogan Emre Sert"},{id:"243593",title:"Dr.",name:"Nesrin",middleName:null,surname:"Turan",slug:"nesrin-turan",fullName:"Nesrin Turan"}]}],onlineFirstChaptersFilter:{topicId:"984",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81437",title:"Pediatric Heart Transplantation",slug:"pediatric-heart-transplantation",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104518",abstract:"Despite advances in medical management, patients submitted for heart transplantation procedures still are at risk to development of complications. This chapter will discuss some specific topics of pediatric heart transplantation, focusing on perioperative care: (i) recipient management, (ii) donor evaluation, (iii) immunosuppression, (iv) early postoperative management, (v) complications, and (vi) conclusions.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Estela Azeka"},{id:"81451",title:"Donor Assessment and Management for Heart Transplantation",slug:"donor-assessment-and-management-for-heart-transplantation",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.104504",abstract:"For many years, heart transplantation has been an established procedure for patients with end-stage heart failure using the so-called “Standard Criteria” for an optimal heart donor. However, annually listed patients for heart transplantation greatly increased worldwide, and the use of extended criteria donor hearts has been utilized as many as possible in many countries. In this chapter, firstly, pathophysiology of brain death is explained. Secondly, donor assessment and issues of extended criteria donors are introduced. Then, donor management to maximize the heart graft availability, and the Japanese donor assessment and evaluation system and its outcome are reviewed.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Norihide Fukushima"},{id:"81057",title:"Induction Therapy in the Current Immunosuppressive Therapy",slug:"induction-therapy-in-the-current-immunosuppressive-therapy",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.103746",abstract:"The current immunosuppressive therapy including calcineurin inhibitors, mycophenolate mofetil, and steroids, has substantially suppress rejections and improved clinical outcomes in heart transplant (HTx) recipients. Nevertheless, the management of drug-related nephrotoxicity, fatal acute cellular rejection (ACR), antibody-mediated rejection and infections remains challenging. Although previous some studies suggested that perioperative induction immunosuppressive therapy may be effective for the suppressing ACR and deterioration of renal function, increased incidence of infection and malignancy was concerned in recipients with induction immunosuppressive therapy. The international society of heart and lung transplantation (ISHLT) guidelines for the care of heart transplant recipients do not recommend routine use of induction immunosuppressive therapy, except for the patients with high risk of acute rejection or renal dysfunction, however, appropriate therapeutic regimen and indication of induction immunosuppressive therapy remains unclear in HTx recipients. We review current evidence of induction immunosuppressive therapy in HTx recipients, and discuss the appropriate therapeutic regimen and indication of induction therapy.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Takuya Watanabe, Yasumasa Tsukamoto, Hiroki Mochizuki, Masaya Shimojima, Tasuku Hada, Satsuki Fukushima, Tomoyuki Fujita and Osamu Seguchi"},{id:"80305",title:"Hepatic and Endocrine Aspects of Heart Transplantation",slug:"hepatic-and-endocrine-aspects-of-heart-transplantation",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.102418",abstract:"End-organ dysfunction is a progression that can often develop in patients with end-stage heart failure. Hepatic abnormalities in advanced systolic heart failure may affect several aspects of the liver function. Hepatic function is dependent on age, nutrition, previous hepatic diseases, and drugs. The hepatic dysfunction can have metabolic, synthetic, and vascular consequences, which strongly influence the short- and long-term results of the transplantation. In this chapter, the diagnostic and treatment modalities of the transplanted patient will be discussed. On the other hand, endocrine abnormalities, particularly thyroid dysfunction, are also frequently detected in patients on the waiting list. Endocrine supplementation during donor management after brain death is crucial. Inappropriate management of central diabetes insipidus, hyperglycemia, or adrenal insufficiency can lead to circulatory failure and graft dysfunction during procurement. Thyroid dysfunction in donors and recipients is conversely discussed.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Andrea Székely, András Szabó and Balázs Szécsi"},{id:"79970",title:"The Role of Large Impella Devices in Temporary Mechanical Circulatory Support for Patients Undergoing Heart Transplantation",slug:"the-role-of-large-impella-devices-in-temporary-mechanical-circulatory-support-for-patients-undergoin",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.101680",abstract:"Large microaxial pump systems (Impella 5.0, or Impella 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) have gained increasing levels of attendance as valuable tools of mechanical circulatory support (MCS). Patients undergoing heart transplantation (HTX) often need temporary MCS in the perioperative course, either as a preoperative bridge or occasionally in the early post-transplant period. Here we present our experience using Impella 5+ support for patients designated to undergo HTX, describe technical aspects of implantation and removal, and further analyze factors influencing the overall patient outcome. Significant factors are discussed in front of the background of contemporary international literature, and current scientific questions are highlighted.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Yukiharu Sugimura, Sebastian Bauer, Moritz Benjamin Immohr, Arash Mehdiani, Hug Aubin, Ralf Westenfeld, Udo Boeken, Artur Lichtenberg and Payam Akhyari"},{id:"80721",title:"Gene Therapy for Cardiac Transplantation",slug:"gene-therapy-for-cardiac-transplantation",totalDownloads:64,totalDimensionsCites:0,doi:"10.5772/intechopen.102865",abstract:"Gene therapy is an advanced treatment approach that alters the genetic composition of cells to confer therapeutic protein or RNA expression to the target organ. It has been successfully introduced into clinical practice for the treatment of various diseases. Cardiac transplantation stands to benefit from applications of gene therapy to prevent the onset of post-transplantation complications, such as primary graft dysfunction, cardiac allograft vasculopathy, and rejection. Additionally, gene therapy can be used to minimize or potentially eliminate the need for immunosuppression post-transplantation. Several animal models and delivery strategies have been developed over the years with the goal of achieving robust gene expression in the heart. However, a method for doing this has yet to be successfully translated into clinical practice. The recent advances in ex vivo perfusion for organ preservation provide potential ways to overcome several barriers to achieving gene therapy for cardiac transplantation into clinical practice. Optimizing the selection of the gene-carrying vector for gene delivery and selection of the therapeutic gene to be conferred is also crucial for being able to implement gene therapy in cardiac transplantation. Here, we discuss the history and current state of research on gene therapy for cardiac transplantation.",book:{id:"11236",title:"Heart Transplantation - New Insights in Therapeutic Strategies",coverURL:"https://cdn.intechopen.com/books/images_new/11236.jpg"},signatures:"Michelle Mendiola Pla, Yuting Chiang, Jun-Neng Roan and Dawn E. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",isOpenForSubmission:!0,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"28",title:"Animal Reproductive Biology and Technology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/28.jpg",isOpenForSubmission:!0,editor:{id:"177225",title:"Prof.",name:"Rosa Maria Lino Neto",middleName:null,surname:"Pereira",slug:"rosa-maria-lino-neto-pereira",fullName:"Rosa Maria Lino Neto Pereira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9wkQAC/Profile_Picture_1624519982291",biography:"Rosa Maria Lino Neto Pereira (DVM, MsC, PhD and) is currently a researcher at the Genetic Resources and Biotechnology Unit of the National Institute of Agrarian and Veterinarian Research (INIAV, Portugal). 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She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. 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He is also Member of the Laboratory of genetic, animal and feed resource and member of Animal science Department of INAT. He graduated from Higher School of Agriculture of Mateur, University of Carthage, in 2002 and completed his masters in 2006. Dr. M’HAMDI completed his PhD thesis in Genetic welfare indicators of dairy cattle at Higher Institute of Agronomy of Chott-Meriem, University of Sousse, in 2011. He worked as assistant Professor of Genetic, biostatistics and animal biotechnology at INAT since 2013.",institutionString:null,institution:null}]},{type:"book",id:"8460",title:"Reproductive Biology and Technology in Animals",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8460.jpg",slug:"reproductive-biology-and-technology-in-animals",publishedDate:"April 15th 2020",editedByType:"Edited by",bookSignature:"Juan Carlos Gardón Poggi and Katy Satué Ambrojo",hash:"32ef5fe73998dd723d308225d756fa1e",volumeInSeries:4,fullTitle:"Reproductive Biology and Technology in Animals",editors:[{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. Dr. Serra\\'s current projects are soil organic matter, soil phosphorus fractions, compositional nutrient diagnosis (CND) and isometric log ratio (ilr) transformation in compositional data analysis.",institutionString:"Brazilian Agricultural Research Corporation",institution:{name:"Brazilian Agricultural Research Corporation",country:{name:"Brazil"}}}]}},subseries:{item:{id:"9",type:"subseries",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11405,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,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",slug:"cecilia-cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",slug:"gil-goncalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",slug:"johann-f.-osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",slug:"mani-t.-valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",slug:"marco-chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"81644",title:"Perspective Chapter: Ethics of Using Placebo Controlled Trials for Covid-19 Vaccine Development in Vulnerable Populations",doi:"10.5772/intechopen.104776",signatures:"Lesley Burgess, Jurie Jordaan and Matthew Wilson",slug:"perspective-chapter-ethics-of-using-placebo-controlled-trials-for-covid-19-vaccine-development-in-vu",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"SARS-CoV-2 Variants - Two Years After",coverURL:"https://cdn.intechopen.com/books/images_new/11573.jpg",subseries:{id:"6",title:"Viral Infectious Diseases"}}}]},publishedBooks:{paginationCount:0,paginationItems:[]},testimonialsList:[{id:"8",text:"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality.",author:{id:"202192",name:"Catrin",surname:"Rutland",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",slug:"catrin-rutland",institution:{id:"134",name:"University of Nottingham",country:{id:null,name:"United Kingdom"}}}},{id:"27",text:"The opportunity to work with a prestigious publisher allows for the possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht University",country:{id:null,name:"Netherlands"}}}}]},submityourwork:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],subseriesList:[],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/51379",hash:"",query:{},params:{id:"51379"},fullPath:"/chapters/51379",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)}()