Merits and demerits of different 3D cell culture techniques.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"5834",leadTitle:null,fullTitle:"Role of Neutrophils in Disease Pathogenesis",title:"Role of Neutrophils in Disease Pathogenesis",subtitle:null,reviewType:"peer-reviewed",abstract:"This book highlights the important role of neutrophils in health as well as in the pathogenesis of various diseases. Section 1 provides a general background information regarding the mechanisms and various triggers of neutrophil extracellular traps (NETs) formation and their role in various infectious and noninfectious diseases (such as postinjury inflammation). Section 2 provides recent evidence regarding the role of neutrophils in the pathogenesis as well as a therapeutic target for selected disease conditions such as periodontal diseases, rheumatoid arthritis, and cystic fibrosis. Section 3 describes the anti-inflammatory properties of neutrophils with focus regarding their role in graft versus host disease. This book provides a wider picture with regard to the importance of this immune cell type in various diseases with focus on one of its recently discovered properties, NETs. Therapeutic targets aimed to modulate neutrophil functions might provide novel approaches in the treatment of various diseases of infectious and noninfectious origin.",isbn:"978-953-51-3196-0",printIsbn:"978-953-51-3195-3",pdfIsbn:"978-953-51-4800-5",doi:"10.5772/65581",price:119,priceEur:129,priceUsd:155,slug:"role-of-neutrophils-in-disease-pathogenesis",numberOfPages:180,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a626ce289341f74b7e3bba3bbcfb2aea",bookSignature:"Maitham Abbas Khajah",publishedDate:"June 7th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5834.jpg",numberOfDownloads:13950,numberOfWosCitations:24,numberOfCrossrefCitations:21,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:77,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 10th 2016",dateEndSecondStepPublish:"October 31st 2016",dateEndThirdStepPublish:"January 27th 2017",dateEndFourthStepPublish:"April 27th 2017",dateEndFifthStepPublish:"June 26th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Kuwait University",institutionURL:null,country:{name:"Kuwait"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1029",title:"Hemorheology",slug:"hemorheology"}],chapters:[{id:"54970",title:"Neutrophil Extracellular Traps in Infectious Human Diseases",doi:"10.5772/intechopen.68443",slug:"neutrophil-extracellular-traps-in-infectious-human-diseases",totalDownloads:2050,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Neutrophils, as the main cells of the first line of host defense against microbial pathogens, are responsible for pathogen recognition, inhibition of pathogen spreading into the host tissue, and finally, killing the invader cells. Neutrophils carry out these functions via numerous mechanisms, including a relatively recently described activity based on a release of neutrophil extracellular traps (NETs), a process called netosis. NETs are structures composed of DNA backbone, decorated with antimicrobial factors, derived from neutrophil granules. The structure of NETs and their enzymatic and microbicidal inclusions enable efficient trapping and killing of microorganisms within the neutrophil extracellular space. However, the efficiency of NETs depends on neutrophil ability to recognize pathogen signals and to trigger rapid responses. In this chapter, we focus on possible pathways involved in the release of NETs and summarize the current knowledge on triggers of this process during bacterial, fungal, protozoan, and viral infections. We also consider the mechanisms used by microorganisms to evade NET-killing activity and analyze the harmful potential of NETs against the host cells and the contribution of NETs to noninfectious human diseases.",signatures:"Marcin Zawrotniak, Andrzej Kozik and Maria Rapala‐Kozik",downloadPdfUrl:"/chapter/pdf-download/54970",previewPdfUrl:"/chapter/pdf-preview/54970",authors:[{id:"198701",title:"Associate Prof.",name:"Maria",surname:"Rapala-Kozik",slug:"maria-rapala-kozik",fullName:"Maria Rapala-Kozik"},{id:"200044",title:"Dr.",name:"Marcin",surname:"Zawrotniak",slug:"marcin-zawrotniak",fullName:"Marcin Zawrotniak"},{id:"200045",title:"Prof.",name:"Andrzej",surname:"Kozik",slug:"andrzej-kozik",fullName:"Andrzej Kozik"}],corrections:null},{id:"55192",title:"Beneficial and Deleterious Effects of Neutrophil Extracellular Traps on Infection",doi:"10.5772/intechopen.68634",slug:"beneficial-and-deleterious-effects-of-neutrophil-extracellular-traps-on-infection",totalDownloads:1542,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Polymorphonuclear neutrophils (PMNs) are the most abundant leukocytes in the blood and are considered as the first line of innate immune defence against infectious diseases. However, PMN cells have a crucial function in both innate and adaptive immune responses. Neutrophils have several mechanisms to control pathogens, and one of them is their capability to form neutrophil extracellular traps (NETs) that may control infection. NETs have the capacity to trap microorganisms, kill them, or avoid their dissemination. The aim of this chapter is to provide a comprehensive review on NETs, the cells that produce them, and some of the mechanisms involved in their formation, their role in the immune response, and the pros and cons of NETs, focusing mainly on infectious diseases.",signatures:"Maximina B. Moreno-Altamirano, Christian E. Cruz-Gómez and\nLluvia E. López-Luis",downloadPdfUrl:"/chapter/pdf-download/55192",previewPdfUrl:"/chapter/pdf-preview/55192",authors:[{id:"197287",title:"D.Sc.",name:"MMaximinaBertha",surname:"Moreno-Altamirano",slug:"mmaximinabertha-moreno-altamirano",fullName:"MMaximinaBertha Moreno-Altamirano"},{id:"206922",title:"Mr.",name:"Christian Eduardo",surname:"Cruz-Gómez",slug:"christian-eduardo-cruz-gomez",fullName:"Christian Eduardo Cruz-Gómez"},{id:"206923",title:"Ms.",name:"Lluvia E",surname:"López-Luis",slug:"lluvia-e-lopez-luis",fullName:"Lluvia E López-Luis"}],corrections:null},{id:"55371",title:"The Role of Neutrophil Extracellular Traps in Post‐Injury Inflammation",doi:"10.5772/intechopen.68906",slug:"the-role-of-neutrophil-extracellular-traps-in-post-injury-inflammation",totalDownloads:1671,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Polymorphonuclear (neutrophil) granulocytes (PMNs) are an essential part of the innate immune responses and key instigators and effectors of the underlying pathological mechanisms (endothelial damage, interstitial histolysis, cytokine production, phagocytosis) leading to post-injury inflammation and secondary tissue injury. In 2004, the formation of neutrophil extracellular traps (NETs) was identified as an additional defence mechanism of PMN against microbes. The understanding of complex regulation of neutrophil functions and NET formation is essential for differentiating between healthy and pathological inflammatory response, which frequently determines if patient recovers uneventfully or develops catastrophic complications. Recent discoveries have revealed the potential role of NETs in the pathogenesis of a wide range of non-infectious diseases, including post-injury sterile inflammation. In such conditions, both spontaneous NET formation and impaired NETosis are documented. In this chapter, we review the evidence for the role of NETs in post-injury inflammation, the key molecular and cellular participants in pathological NET formation, the clinical relevance of NETs in post-injury complications and the therapeutic potential of NET inhibition/clearance.",signatures:"Eszter Tuboly, Gabrielle D. Briggs and Zsolt J. Balogh",downloadPdfUrl:"/chapter/pdf-download/55371",previewPdfUrl:"/chapter/pdf-preview/55371",authors:[{id:"26682",title:"Prof.",name:"Zsolt",surname:"Balogh",slug:"zsolt-balogh",fullName:"Zsolt Balogh"},{id:"205370",title:"Ph.D.",name:"Gabrielle",surname:"Briggs",slug:"gabrielle-briggs",fullName:"Gabrielle Briggs"}],corrections:null},{id:"54543",title:"Neutrophil Role in Periodontal Disease",doi:"10.5772/67789",slug:"neutrophil-role-in-periodontal-disease",totalDownloads:3050,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Oral tissues are constantly exposed to damage from the mechanical effort of eating and from the invasion of foreign microorganisms such as bacteria, fungi, and virus. In healthy oral tissues, there is a balance between symbiotic bacteria and cells from the innate immune system, mainly neutrophils. When this balance is broken, inflammation appears and more immune cells are recruited to the gingiva. Neutrophils form a barrier against dysbiotic bacteria. However, when neutrophils are insufficient, bacteria thrive causing periodontitis, a chronic inflammatory disease that destroys the tooth‐supporting tissues or periodontium. Damage of periodontal tissues leads to tooth loss, and in severe cases, it can also affect systemic health by increasing a person's risk for atherosclerosis, rheumatoid arthritis, diabetes, and even cancer. The mechanisms neutrophil employ to keep a balance with bacteria in order to maintain healthy oral tissues is the focus of this chapter. We discuss how neutrophil antimicrobial functions keep bacteria at check and how some dysbiotic bacteria block neutrophils to promote an inflammatory state. Also, novel therapeutic approaches for periodontitis are discussed.",signatures:"Carlos Rosales and Eileen Uribe‐Querol",downloadPdfUrl:"/chapter/pdf-download/54543",previewPdfUrl:"/chapter/pdf-preview/54543",authors:[{id:"192432",title:"Dr.",name:"Carlos",surname:"Rosales",slug:"carlos-rosales",fullName:"Carlos Rosales"},{id:"198687",title:"Dr.",name:"Eileen",surname:"Uribe-Querol",slug:"eileen-uribe-querol",fullName:"Eileen Uribe-Querol"}],corrections:null},{id:"55356",title:"Neutrophils in Rheumatoid Arthritis: A Target for Discovering New Therapies Based on Natural Products",doi:"10.5772/intechopen.68617",slug:"neutrophils-in-rheumatoid-arthritis-a-target-for-discovering-new-therapies-based-on-natural-products",totalDownloads:2071,totalCrossrefCites:9,totalDimensionsCites:12,hasAltmetrics:0,abstract:"Rheumatoid arthritis (RA) is a systemic autoimmune disorder with an important inflammatory component in joints. Neutrophils are the most abundant leukocytes in inflamed joints, and play an essential role in the initiation and progression of RA. Neutrophil effector mechanisms include the release of proinflammatory cytokines, reactive oxygen and nitrogen species (ROS and RNS), and granules containing degradative enzymes, which can cause further damage to the tissue and amplify the neutrophil response. Therefore, the modulation of neutrophil migration and functions is a potential target for pharmacological intervention in arthritis. The pharmacologic treatment options for RA are diverse. The current treatments are mostly symptomatic and have side effects, high costs, and an increased risk of malignancies. Because of these limitations, there is a growing interest in the use of natural products as therapies or adjunct therapies. Herbal products have attracted considerable interest over the past decade because of their multiple beneficial effects such as their antioxidant, anti-inflammatory, antiproliferative, and immunomodulatory properties. This chapter focuses on the role of neutrophils in the pathogenesis of arthritis and the action of substances from natural products as putative antirheumatic therapies.",signatures:"Elaine Cruz Rosas, Luana Barbosa Correa and Maria das Graças\nHenriques",downloadPdfUrl:"/chapter/pdf-download/55356",previewPdfUrl:"/chapter/pdf-preview/55356",authors:[{id:"64332",title:"Dr.",name:"Maria Das Graças",surname:"Henriques",slug:"maria-das-gracas-henriques",fullName:"Maria Das Graças Henriques"},{id:"197932",title:"Dr.",name:"Elaine",surname:"Rosas",slug:"elaine-rosas",fullName:"Elaine Rosas"},{id:"199677",title:"MSc.",name:"Luana",surname:"Correa",slug:"luana-correa",fullName:"Luana Correa"}],corrections:null},{id:"54594",title:"Role of Neutrophils in Cystic Fibrosis Lung Disease",doi:"10.5772/67798",slug:"role-of-neutrophils-in-cystic-fibrosis-lung-disease",totalDownloads:1700,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Cystic fibrosis (CF) is a genetic syndrome caused by mutations in the CF Transmembrane Conductance Regulator (CFTR) gene. In CF patients, chief morbidity and mortality are due to pulmonary manifestations. CFTR lack/dysfunction brings an altered ion flux through the airway epithelium and ablation of mucociliary clearance, which in turn ensues in colonization and infection by opportunistic bacterial pathogens and subsequent neutrophil‐dominated inflammation. This response eventually leads to the damage of the lung tissue. A host of inflammatory mediators attract, activate, and reprogramme neutrophils to survive (avoiding apoptosis) and produce a wealth of proteases and radical oxygen species. The protease/antiprotease imbalance and oxidative stress have multiple downstream effects, including impaired mucus clearance, increased and self‐perpetuating inflammation, and impaired immune responses, thus facilitating and fostering bacterial infections. On the other hand, CFTR lack or dysfunction is likely responsible for alterations in neutrophils concerning chemotaxis, phagocytosis, oxidative burst, degranulation, and neutrophil extracellular trap (NET) formation. A good opportunity to reveal new and non‐invasive biomarkers of CF lung disease is the evaluation of circulating neutrophils. Indeed, neutrophil responses are now investigated as outcomes of the aetiological therapies in CF, such as hypertonic saline, antiproteases, CFTR correctors and potentiators.",signatures:"Massimo Conese, Stefano Castellani, Susanna D’Oria, Sante Di Gioia\nand Pasqualina Montemurro",downloadPdfUrl:"/chapter/pdf-download/54594",previewPdfUrl:"/chapter/pdf-preview/54594",authors:[{id:"198848",title:"Prof.",name:"Massimo",surname:"Conese",slug:"massimo-conese",fullName:"Massimo Conese"},{id:"199817",title:"Prof.",name:"Stefano",surname:"Castellani",slug:"stefano-castellani",fullName:"Stefano Castellani"},{id:"199818",title:"Dr.",name:"Susanna",surname:"D'Oria",slug:"susanna-d'oria",fullName:"Susanna D'Oria"},{id:"199819",title:"Prof.",name:"Sante",surname:"Di Gioia",slug:"sante-di-gioia",fullName:"Sante Di Gioia"},{id:"199820",title:"Prof.",name:"Pasqualina",surname:"Montemurro",slug:"pasqualina-montemurro",fullName:"Pasqualina Montemurro"}],corrections:null},{id:"54763",title:"Neutrophils Plasticity: The Regulatory Interface in Various Pathological Conditions",doi:"10.5772/68130",slug:"neutrophils-plasticity-the-regulatory-interface-in-various-pathological-conditions",totalDownloads:1866,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:0,abstract:"It is now known that neutrophils make up a population of complex cells with great plasticity, challenging the old view of neutrophil association with tissue damage and early phases of infection. Here, we discuss different contexts in which these cells can induce anti-inflammatory responses. Although distinct surface markers and cytokines profiles were shown, the most reliable characterization of suppressor neutrophil subtypes relies on their functional characteristics. One important example of inhibitory neutrophils generation comes from in vivo treatment with G-CSF, for 5 days, as for hematopoietic-stem-cell-transplantation (HSCT). In this case,donor blood is enriched in degranulated granulocytes harboring a functional regulatory phenotype, characterized by IL-10 production. These cells, when transferred together with HSCT, are able to reduce graft-versus-host-disease, being influenced by Treg cells and influencing them back. Importantly, this protection is long lasting and specific, keeping immunocompetence to other antigens. This regulation is paramount in HSCT, and represents a simple approach to be applied in humans. In summary, we discuss the interaction of neutrophils with other cell types and its consequence in immunomodulation. We believe these features confer an important bridge between innate and adaptive immune system, building a new knowledge for an underestimated cell type.",signatures:"Suelen Martins Perobelli, Triciana Gonçalves Silva and Adriana\nBonomo",downloadPdfUrl:"/chapter/pdf-download/54763",previewPdfUrl:"/chapter/pdf-preview/54763",authors:[{id:"170492",title:"Dr.",name:"Adriana",surname:"Bonomo",slug:"adriana-bonomo",fullName:"Adriana Bonomo"},{id:"205632",title:"Dr.",name:"Suelen",surname:"Perobelli",slug:"suelen-perobelli",fullName:"Suelen Perobelli"},{id:"205633",title:"MSc.",name:"Triciana",surname:"Gonçalves-Silva",slug:"triciana-goncalves-silva",fullName:"Triciana Gonçalves-Silva"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7129",title:"Neutrophils",subtitle:null,isOpenForSubmission:!1,hash:"4f71e75cb45249658d48e765d179ce9f",slug:"neutrophils",bookSignature:"Maitham Khajah",coverURL:"https://cdn.intechopen.com/books/images_new/7129.jpg",editedByType:"Edited by",editors:[{id:"173123",title:"Dr.",name:"Maitham",surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2607",title:"Blood Cell",subtitle:"An Overview of Studies in Hematology",isOpenForSubmission:!1,hash:"7c47fe55b6adb4aaadb74f8e977e46e5",slug:"blood-cell-an-overview-of-studies-in-hematology",bookSignature:"Terry E. 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Hair loss is the most common hair disease and diagnosis of the type of alopecia may sometimes be challenging. Methods commonly used to investigate can be classified as either invasive (e.g., biopsies in scarring alopecia), semi‐invasive (trichogram, unit areatrichogram), or noninvasive (e.g., hair count, weighing shed hair, pull test, global hair counts, dermoscopy, phototrichogram, electron microscopy, laser scanning microscopy) methods. In this chapter, I will try to explain the basics of trichoscopy and trichogram.
Scalp dermoscopy is a simple and noninvasive instrument for appraising a number of hair and scalp disorders. Scalp dermoscopy, which may be defined as “trichoscopy” [1–3] is widely used in dermatology for the evaluation of pigmented skin lesions, represents a valuable, noninvasive, and rapid technique for the assessment of patients with hair loss that allows for a magnified visualization of the hair and scalp skin [4–7]. Trichoscopy allows for magnified observation of the following: hair shafts, hair follicle openings, the perifollicular epidermis, and blood vessels. In particular, trichoscopy may be useful for the diagnosis, prognosis and follow‐up of androgenetic alopecia (AGA), alopecia areata (AA), telogen effluvium (TE), trichotillomania, congenital triangular alopecia, tinea capitis, cicatritial alopecias, and hair shaft disorders [8, 9]. Dermoscopy may be performed with a manual dermoscope (10× magnification) or videodermoscope (up to 1000× magnification) [10]. Both polarized and nonpolarized light may be used, with or without the use of immersion oil (dry dermoscopy).
\nBoth handheld dermatoscope and videodermatoscope is suitable to perform trichoscopy. Handheld dermatoscopes allow for tenfold magnification, while the magnification of digital dermatoscopes is ranging from tenfold to 50‐fold and higher. Handheld dermatoscopes have the advantage of being both time and cost‐effective. On the other hand, digital dermatoscopes have the superiority of taking easier photography and having higher magnifications [5]. I prefer using videodermatoscope that allows vascular structures more obvious [8, 9]. Water, ultrasound gels, aqueous gels, liquid paraffin, alcohol, and oil can be used to enhance clarity and visualization [11]. The choice of a particular device and fluid immersion is a matter of individual preference.
\nTrichoscopy images can be used to assess hair shaft thickness by folliscope [12] or analyzing hair growth by trichoscan [13] while trichoscan has been criticized by some dermatologists for the need of shaving and dying hair in the analyzed area [14, 15]. These images may be used to obtain optimal areas for scalp biopsy in cicatricial alopecia [16].
Normal scalp is characterized by the presence of follicular units containing about 2–4 terminal hairs and 1 or 2 vellus hairsof uniform thickness and color [17–20]. The mean thickness of normal hair was about 0.06 mm [19]; however, up to 10% of hairs are represented by vellus hairs which lack the medulla [6, 21, 22]. A normal terminal hair is uniform in thickness and color throughout its length, however, vellus hairsare lightly pigmented [21, 22]. Simple, fine red loops, which represent capillaries within the dermal papillae, are generally visible among hairs, and the subpapillary plexus is visible as linear arborizing vessels. In dark‐skinned individuals, a perifollicular pigmented network (honeycomb pattern) is usually appreciated over the scalp which is accentuated over sun‐exposed areas, and follicular openings and ecrine sweat gland duct openings appear as white dots (WD) [7, 23].
Trichoscopy may distinguish whether hair follicle openings are normal, empty, fibrotic,or containing biological material, such as hyperkeratotic plugs or hair residues. “Dots” is a common term for small, round hair follicle openings seen by trichoscopy [5, 6, 24].
\nPrevious studies showed that yellow dots (YD) indicates dilated infundibula of follicles with remnants of hair [25–28, 41] and follicular openings filled with keratotic material and/or sebum [24, 29]. They vary in color, shape and size. Regularly distributed YD are present in 60% of patients with AA and are considered a marker of disease severity and less favorable prognosis [24] while there was no relation with disease severity according to our study [30]. Yellow dots are present in AA [24, 30] discoid lupus erythematosus (DLE), TE [28, 30], and AGA [19, 28]. Large, dark yellow to brownish YD (keratotic plugs) are characteristic of DLE and correspond to wide infundibula filled with keratotic material [31, 32] although we saw these brown dots in patients with AGA at the same time [28]. Yellow dots are also seen in patients with patterned hair loss, YD in the frontal area compared to the occipital area favors the diagnosis of female AGA [19], they differ from the YD observed in other diseases by their “oily” appearance that most probably results from the predominance of sebum over keratotic material [9].
\nYellow dots imposed over dark hair shaft residues appearing as large “3D” soap bubbles have been described in dissecting cellulitis [31] and in trichotillomania [24]. According to some dermatologists [5], when there is no suspicion of AGA, if you see YD, the diagnosis of AA incognita is obvious to differ AA incognita from TE and trichotillomania. On the other hand, in addition to these diseases, YD may be seen in patients with TE, trichotillomania, psoriasis, and seborrheic dermatitis [28, 30].
Yellow dots are firstly described by Ross and colleagues [5] as uniform structures yellowish‐pink in color, while some of these dots were found to be brown in color in our patients [28, 30]. Brown dots were found with a statistically higher frequency in patients with AGA [30]. Scattered brown areas are seen in actinic keratosis and DLE, and peripilar brown areas are seen in AGA, in TE and in healthy individuals, simply sometimes, we can see brown dots in a distribution similar to YD in dark‐skinned patients [8, 28, 30], and therefore, I call them yellow‐brown dots instead of YD as a separate category.
Black dots (formerly “cadaverized hairs”) are residues of pigmented hairs that have been broken or destroyed at the level of the scalp [33]. They are considered a marker of high disease activity while there was no relationship during our study [24, 30]. Black dots may be present in dissecting cellulitis, tinea capitis, chemotherapy‐induced alopecia, trichotillomania, but may be incidentally observed also in other diseases and after laser depilation or trichogram [33, 34]. Black dots are not present in healthy individuals or in patients with patterned hair loss or TE [4, 28, 30, 35].
Black dots sized smaller than declared black dots (cadaverized hairs) those are seen in AA previously [30] were named as black dotted pigmentation (BDP) by us, and they related positively with disease severity in AA. A biopsy from one of these areas in a patient with AA showed no cellular infiltration but revealed intense demodex colonization in follicular ostia, so it was thought that the trichoscopic appearance might be due to this infestation. In a study [36], dirty dots on scalp represented nonmicrobial environmental particles in healthy children.
Red dots are widened follicles surrounded by dilated vessels and extravasated erythrocytes were described in DLE and are believed to be a positive prognostic factor [29]. Regularly distributed brown or brown‐gray dots are a characteristic finding in the eyebrow area of patients with frontal fibrosing alopecia (FFA). This finding is a favorable prognostic factor for eyebrow regrowth [6]. Additionally, red dots have been described in individuals with vitiligo [37].
Pink‐grey and grey dots have been observed in the eyebrow area of patients with FFA [9].
The classic, big, irregular WD represent areas of perifollicular fibrosis and are observed most commonly in lichen planopilaris (LPP) [6]. Another type of WD, the small, regular pinpoint WD are observed in the sun‐exposed scalp of patients with skin phototypes III and IV and in the normal scalp of those with phototypes V and VI [6, 28, 30, 38]. They have been correlated with the acrosyringeal (ecrine sweat duct openings) and empty follicular openings [38–40]. According to us, another type of WD are cumulus like clustered WD that are intersecting WD in a nested form. We think in severe AA the classic, irregular WD is nested together with pinpoint WD, so we call them clustered WD similar to cumulus clouds [30]. In advanced stages of AGA, follicles can be replaced by connective tissues, afterwards causing atrophy. These empty follicular ostia are seen as WD [5, 19, 24, 28, 30, 31, 38, 39]. WD are more common in the late stages of AGA [5, 28]. Kossard and Zagarella [42] observed WD in scarring alopecia and considered these WD as being the melanin pour places in fibrous tracts of scar tissue.
Abnormalities in hair shaft structure may provide diagnostic clues for multiple acquired and inherited causes of hair loss. Rudnicka et al. recently proposed a classification of hair shaft abnormalities observed by trichoscopy [18, 43–45]. The features of hair shafts include exclamation mark hair in AA, trichotillomania, and chemotherapy‐induced alopecia (also called “tapering hairs “: 1‐ to 2‐mm‐long fractured hairs, whose tips are wider than the proximal portion of the shaft), broken hairs (fractured hairs with uniform shaft diameter), vellus hairs in patterned hair loss and in long‐lasting AA (less than 0.03 mm in thickness and less than 3‐mm long, representing miniaturized hairs or regrowing hairs can be differentiated from short, healthy regrowing hairs, which are darkly pigmented and straight with pointed ends), coiled hairs in trichotillomania (broken hairs that curl back), comma hairs (short, c‐shaped hairs), and cork screw hairs in tinea capitis (short hairs, spiral in shape), Pohle Pinkus constrictions in AA, chemotherapy‐induced alopecia, blood loss, malnutrition, and chronic intoxication, flame hairs (semitransparent, wavy, and cone‐shaped highly specific hair residues, resembling a fire flame that remain attached to the scalp after anagen hairs have been pulled out), V‐signs (two or more hairs emerging from one follicular unit and broken at the same length),and sprinkled hairs (only a sprinkled “hair powder”, resulting from hair damage, is visible) in trichotillomania, and tulip hairs (diagonally fractured short hair shafts with a tulip leaf‐like hyperpigmentation at the distal end] in trichotillomania and AA [43, 44]. Trichoscopy has also been successfully used to diagnose many genetic hair shaft disorders [45].
According to the color and structure (scaling, discharge, and surface structure) of the areas, the classification of perifollicular and interfollicular skin surface abnormalities in trichoscopy can be classified as; perifollicular discoloration (hyperpigmentation), predominant in androgenetic alopecia,and perifollicular fibrosis, characteristic for some form of fibrosing alopecia [8, 46].
\nDue to epidermal and perifollicular inflammation in seborrheic dermatitis and psoriasis [47, 48], proximal hair shaft with macropits [49] may look relatively hidden under a white‐grey epidermal diffuse proliferation that we called as hidden hair [50] that differs from perifollicular scaling observed in LPP and in folliculitis decalvans [6, 31].
\nDuring our knowledge, honeycomb hyperpigmentation is a normal finding in sun‐exposed areas (chronic sun exposure) and in patients with Fitzpatrick skin phototypes IV, V, and VI [5–7], but in our study, when this pattern is observed trichoscopically, the estimated alopecia risk was 3.2 times higher regardless of age that is why, we do not think it is the characteristic of normal aging scalp [28]. Perifollicular brown coloration (“peripilar sign”) is believed to correspond to the perifollicular presence of lymphocytic infiltrates [51] and is common in patients with patterned hair loss [2]; however, the peripilar sign may be observed in up to10% of hair follicles in healthy individuals [21]. Scattered brown discoloration is characteristic of DLE [31].
Appearance of cutaneous microvessels in trichoscopy may vary in type and number depending on disease and activity of the process. The significance of blood vessel abnormalities observed on trichoscopy has not been explored in detail thus far. Common types of vessels in alopecia includes elongated vessels in LPP, thick arborizing vessels in DLE and seborrheic dermatitis, twisted red loops and comma vessels in seborrheic dermatitis, atypical red vessels, structureless red areas, signet ring vessel, twisted red loops and glomerular or coiled vessels in linear or circular alignment in psoriasis [9, 19, 31, 50, 52].
Other common trichoscopy signs include yellow or yellow‐red discharge (e.g., folliculitis decalvans, bacterial infections, dissecting cellulitis, and tinea capitis) and structural changes in the skin surface (e.g., starburst pattern hyperplasia in folliculitis decalvans) [9, 31].
The most characteristic trichoscopic findings include the following: black dots, exclamation mark hairs, tapered hairs, broken hairs, coudability hairs (hairs of normal length with a narrowed proximal shaft and are mostly found in the scalp surrounding the alopecic patch), coiled hairs, YD, hypopigmented vellus hairs, trichorrhexis nodosa, monilethrix‐like hairs (constrictions in the hair shaft),and Pohle Pinkus constrictions [4–9, 24, 30, 53–57]. Broken hairs are not exclusive to AA, as they may also be observed in trichotillomania [7]. Exclamation mark hairs represent the most specific signs of acute AA [17]; however, they are also observed in chemotherapy alopecia. Black dots may also be observed in trichotillomania, cicatritial alopecia, and tinea capitis. Yellow dots may be observed both in acute and in chronic forms of AA and generally have a regular distribution and in severe forms have a nested formation [5, 7, 24, 30]. Yellow dots are highly sensitive but have low specificity for AA, as they may be seen in other hair disorders, including AGA, congenital hypotrichoses, and DLE [7, 28]. Short, hypopigmented vellus hairs are a common finding in AA and are usually indicative of remitting disease [4, 7].
\nIn our study [30], major risk factors for AA were determined to be black dots, WD, and YD (risk ratios were estimated as 170‐fold, 5.9‐fold,and 5.3‐fold, respectively).
\nActive (acute) AA can be distinguished from nonactive AA using trichoscopy. Features of disease activity include black dots, exclamation marks, broken hairs, trichoptilosis, pig tail, short vellus hairs,and upright regrowing hair whereas YD, WD, clustered WD, honeycomb pigmentation, black dotted pigmentation, and vellus hairs are markers of disease severity and inactive late stage disease [4, 12, 20, 24, 30, 55, 58]. In addition to this, disease activity showed negative relation with atypical red vessels in our study, we believed that these atypical red vessels indicated rejuvenation after the catabolic process in progressive AA [30]. Early features of hair regrowth include the presence of pigmented, upright, regrowing hairs [24], and pigtail hairs [23]. Recent data show that trichoscopy may also be applied in the evaluation of treatment response in AA patients [59].
Male and female pattern hair loss share similar trichoscopic features. These include hair shaft thickness heterogeneity (anisotrichosis, hair diameter diversity), YD, pinpoint WD, honeycomb pigmentation, focal atrichia, epidermal scaling, arborizing red lines, perifollicular brown,and white discoloration (peripilar sign), an increased proportion of vellus hairs, and an increased proportion of follicular units with only 1 emerging hair shaft instead of 2–4 hair shafts [4, 5, 9, 11, 19, 28, 43, 60–63]. On the other hand, in early AGA, we saw multihair follicular unit more than follicular units with only 1 emerging hair shaft [28].
\nTrichoscopy was demonstrated to be superior to the classical trichogram for the evaluation of early female AGA [64], showing 75% sensitivity and 61.54% specificity in a recent study [65].
\nAll of the trichoscopic features appear most prominently in the frontal scalp area [19, 21]. An increased ratio of vellus hairs to all hairs in androgen dependent scalp regions is characteristic of AGA [6, 7, 19, 28]. The most important finding of AGA is the hair diameter variability, which reflects hair miniaturization [44]. Hair miniaturization does not equally affect all hair follicles of the same area, resulting in the simultaneous presence of terminal, intermediate, and vellus hairs. When the hair diameter variability of more than 20%, which means that vellus hairs account for more than 20% of all the hairs in the same view, was regarded as a hallmark of AGA in previous reports [6, 7, 60]. In addition to this, three major diagnostic criteria for female AGA have been suggested: more than four yellow dots in four images (70‐fold magnification) of the frontal area, a lower than average hair thickness in the frontal area compared to the occipital area, and vellus hairs (below 0.03 mm) comprising more than 10% of hairs in the frontal area [19]. Recently, some authors have suggested that the presence of more than six vellus hairs in the frontal scalp may be indicative of initial female AGA [66].
\nIn more advanced and severe stages of AGA, trichoscopy shows the presence of empty follicular ostia, YD, brown dots,and a honeycomb‐like pigmented network in bald, sun‐exposed areas [5, 7, 28, 63].
\nIn our study, PFP was detected to be a characteristic trichoscopic finding of AGA that was described as a normal feature of the scalp in healthy persons younger than 25 years [21, 28].
\nAlthough no specific trichoscopic criteria of TE have been recognized, the diagnosis may be suspected when empty hair follicles (sometimes appearing as YD), a high percentage of follicular units with only 1 hair, brown perifollicular discoloration (the peripilar sign), and short, dark, multiple upright regrowing hairs of normal thickness are present in the absence of the characteristic features of other scalp disorders [7, 19, 40, 67, 68]. In TE patients, no significant differences are observed in the trichoscopic findings between the frontal and occipital areas; this differentiates TE from patterned hair loss [9].
Trichoscopy shows the presence of broken hair shafts of different lengths with no significant changes in the perifollicular area. The extremities of the hairs have a typical frayed aspect (split ends) [69]. Trichoscopy is also useful to demonstrate the signs of plucking to the parents [70]. Recently, a number of other signs, all variants of broken hairs, have been described, including coiled hairs, flame hairs (semitransparent, wavy, and cone‐shaped highly specific hair residues, resembling a fire flame that remain attached to the scalp after anagen hairs have been pulled out), V‐signs (2 or more hairs emerging from one follicular unit and broken at the same length), tulip hairs (diagonally fractured short hair shafts with a tulip leaf‐like hyperpigmentation at the distal end), and sprinkled hairs (only a sprinkled “hair powder”, resulting from hair damage, is visible) [68]. Black dots and exclamation mark hairs may be sometimes observed [6, 57, 68], and it can be very difficult to distinguish these cases from AA.
Trichoscopy shows normal follicular openings, highlights the clinical presence of long, thin vellus hairs that are surrounded by normal terminal hairs in the adjacent scalp and allows for differential diagnosis with AA and cicatritial alopecia [7, 71, 72].
Comma hairs are comma‐like structures that are associated with both ectothrix and endothrix types of fungal invasion [73–76]. In some patients, hairs are more intensely coiled than typical comma hairs. These hairs have been called “corkscrew hairs” [73, 75, 76]. Corkscrew hairs are also observed in patients of African descent who are infected by
Trichoscopic images of anagen effluvium are characterized by the presence of black dots, monilethrix‐like hairs, and exclamation mark hairs [33, 34].
Kim et al. reported that red dots and globules, twisted red loops,and glomerular vessels were mostly seen in psoriasis while atypical red vessels, arborizing red lines,and structureless red areas were seen in seborrheic dermatitis [52]. On the other hand, in our study we observed red dots and globules, atypical red vessels, structureless red areas, hidden hair and signet ring vessel mostly in psoriasis while twisted red loops and comma vessels mostly in seborrheic dermatitis [50]. Twisted red loops are thought to be the characteristic videodermatoscopic figure of scalp psoriasis in comparison with seborrheic dermatitis [5]. On the other hand, we considered red dot and globules as the characteristic videodermatoscopic figure of psoriasis and arborizing red lines for seborrheic dermatitis according to our study [50].
One of the most typical trichoscopic features of active DLE is the presence of large YD that differ from the YD observed in AA by their larger size and darker, yellow‐brownish color [31, 32, 80]. Occasionally, in long‐lasting DLE, thin and radial arborizing vessels are observed to emerge from these dots (“red spider in YD” appearance) which some authors consider a characteristic of DLE [6, 31]. Thick arborizing vessels are commonly present at the periphery of the lesion. Trichoscopic findings for long‐lasting, inactive DLE lesions do not differ from those for other types of cicatricial alopecia and are characterized by structureless milky‐red or white areas lacking follicular openings [31]. When present, red dots, which are regularly distributed around follicular openings, indicate the expression of active disease and are related to a good prognosis with possible hair regrowth upon prompt treatment [29, 31].
Trichoscopy reveals the absence of follicular openings and the presence of whitish perifollicular casts that surround the hair shafts at their emergence as the most characteristic feature [4–7, 31, 81, 82]. Scales migrate along the hair shafts and form tubular structures that cover the proximal portions of the emerging hair shafts. This phenomenon is called tubular perifollicular scaling [31]. Some authors have described the presence of blue‐gray dots arranged in a target pattern around the hair follicles (due to the presence of melanophages) [80]. In dark‐skinned subjects affected by LPP the persistence of a normal pigmented network inside the plaques of hair loss is typical, as the interfollicular epidermis is commonly unaffected by the inflammatory process [83].
\nMilky‐red areas are characteristic for inflammation‐mediated fibrosis of recent onset [31]. Small hair tufts, of 5–9 hairs, may be present in late LPP [31]. To sum up, possible differences between DLE and LPP are the presence of blue‐gray dots with a diffuse distribution along the patch “speckled” pattern, resulting from interface dermatitis and the subsequent pigment incontinence [80] and the loss of the normal pigmented network in dark‐skinned patients due to the involvement of the interfollicular epidermis.
Trichoscopic findings in FFA include the lack of follicular openings and minor perifollicular scaling is lower than that of LPP [84–87]. A characteristic finding of FFA is the abrupt interruption of the hairline, with the absence of the vellus hairs that are typically observed in normal scalp. The background in patients with FFA is usually ivory‐white to ivory‐beige [86, 87]. Pink‐grey and grey dots are commonly observed in the lateral eyebrow area of patients with FFA [9]. To sum up, lonely hairs, surrounded by areas of fibrosis [84], and the absence of vellus hairs in the frontal hairline [85] have been discussed as possible clues for the diagnosis of FFA.
\nTrichoscopy is very helpful in the differential diagnosis with other types of alopecia involving the scalp margin in female patients; in AGA, it shows an increased presence of vellus hairs at the hairline, in FFA, the absence of vellus hairs represented the predominant trichoscopic pattern, followed by perifollicular scaling, and the absence of follicular openings, in ophiasic AA, it shows the typical signs of the disease, while in traction alopecia vellus hairs are preserved [85].
Trichoscopy shows severe pustulation, scaling,and crusting that are generally prominent around follicular units. When cicatritial alopecia occurs, trichoscopy shows the absence of follicular openings and, in cases of tufted folliculitis, the outgrowth of several hairs (hair tufts) from single and dilated residual follicular openings [5, 88, 89] that is the most characteristic trichoscopic feature [82, 90]. Some authors have described the presence of a perifollicular hyperplasia with a typical starburst pattern in such cases. A perifollicular concentration of blood vessels may also be present. In long‐standing disease, white and milky red areas lacking follicular openings are predominant [31].
In early stages, dissecting cellulitis shows trichoscopic features that may be similar to those observed in AA [39]. In a study [54] including 11 patients with dissecting cellulitis, trichoscopy showed the presence of YD, red dots, empty follicular openings,and black dots and may mimic AA [33, 54]. As the diseases progresses, other trichoscopic features become more prominent, including yellow structureless areas and YD with “3‐dimensional” structure imposed over dystrophic hair shafts [31]. Some authors describe these yellow dots with “3D” structure that are imposed over dystrophic hair shafts as the most characteristic feature of dissecting cellulitis [6, 31]. End‐stage fibrotic lesions are characterized by confluent ivory‐white or white areas lacking follicular openings [31, 91].
One article described the trichoscopic aspect of the disease as reduced hair density with hair shaft variability, pinpoint WD, and peripilar white halos. Moreover, pigmented, asterisk‐like macules with sparse terminal and vellus‐like hairs may be present. The residual terminal hairs may emerge as a single hair or as a group of two hairs and are generally surrounded by a characteristic, peripilar gray‐white halo [7].
When using light microscopy, multiple samples may be needed before an abnormal hair shaft is identified therefore trichoscopy may replace light microscopy in the evaluation of genetic hair shaft defects, such as monilethrix [92, 93], trichorrhexis invaginata [94, 95], trichorrhexis nodosa [45], pili annulati [45, 96], pili torti [5, 96], and others [17, 18]. On the other hand, in trichothiodystrophy, the characteristic tiger tail pattern is not visible on trichoscopy, and polarized microscopy remains the criterion standard for diagnosing this condition [9, 45]. When using trichoscopy, different features may be observed in the following disorders:
\nElliptical nodes of normal hair thickness that are regularly separated by dystrophic constrictions in which the hairs have no medulla and that are the sites of fracture; this finding has also been described as the “regularly bended ribbon sign” [10, 45, 92, 93, 96, 97].
Flattened hair shafts with regular twists at irregular intervals along the long axis [10, 92, 96].
Triangular‐shaped shafts with longitudinal grooving or flattening [9].
Alternating light and dark bands, light bands corresponding to air‐filled cavities within the hair shaft [6, 17, 45, 96].
White knots along the distal shafts and brush‐pattern fractured ends [17].
Multiple ball‐shaped nodes along hairs that resemble the ball‐in‐cup rings of bamboo and are due to invagination of the distal portion of the hair shaft into its proximal portion; the fragile node breaking off results in ragged, cupped proximal hair (golf‐tee hairs) [17, 95, 96].
Hair shafts resembling a crawling snake with short wave cycles [45].
Nonhomogeneous structure resembling grains of sand and having a wavy contour [45].
In this procedure, 60–80 hairs are plucked with a rubber‐armed forceps from a 5‐day unwashed hair. Hair bulbs are immediately placed with their roots on a glass slide in an embedding medium, which allows information about the state of the proximal end of the hair shaft (the root), the distal end (the tip) and hair root is necessary [98].
\nThe trichogram is a useful complementary tool for clinical evaluation, diagnosis, and the monitoring of treatment response [99].
\nIt should be noted that the trichogram simply provides a snapshot of the hair follicle at the time of examination and that the condition of follicles can vary within the same patient depending on numerous factors, such as sampling site, previous washing or brushing of the hair, and time of the year [100].
\nAppropriate sampling site for male pattern hair loss should be taken from the central interparietal area, while the second sample, if needed, should be taken from the temporal or occipital area. In female pattern hair loss, samples should be taken from the center and the vertex of the scalp. The sites for telogen hair loss and scarring alopecia are, respectively, the central interparietal area and the advancing border of the alopecic patch. Using a rubber‐sheathed Kocher forceps, a tuft of 15–20 hairs must be removed. To do this, you have to place the forceps 1–2 cm from the scalp and pluck out the hairs rapidly and firmly in the direction of the natural growth of the hair. If the hairs are not plucked out firmly, they may appear as pseudo‐dystrophic hairs under the microscope, or exhibit frayed or broken roots [99].
\nThe next step is to prepare the hairs for examination under the microscope. They should be parallel to each other and that the roots are aligned. Next, they are covered with clear adhesive tape. To avoid artifacts and obtain a sharper, cleaner image, you may apply several drops of balsam (such as that used to mount histological slides) and cover the hairs with a cover slip. The use of polarized light improves image quality [99].
The sample is examined using a 4× objective, although a 10× or 40× objective can be used if higher magnification is needed. A higher‐quality image can be obtained by fitting 2 polarizers to the microscope: 1 between the condenser and the sample and the other between the sample and the observer [99].
\nAnagen hair shafts are longer, have a uniform diameter, a rectangular shape, and a slight distal angle. Pigmentation is intense in the bulb area and there are sheaths and membranes.
\nTelogen hair shafts are shorter and appear higher up in the trichogram, above the roots of anagen hairs; the root is thick and club shaped and there are no distal angles.
\nPigmentation is weak or absent; the sheath is also absent or found only at the distal end.
\nVery few hairs in the catagen phase are observed in the trichogram as they account for a very small percentage of all hair.
\nThe anagen to telogen ratio varies, mainly according to age and sex. Children have the highest percentage of anagen hair (95% anagen vs. 5% telogen), and the ratio decreases with age. The anagen to telogen ratio is 86:11 in women and 83:15 in men. In a normal trichogram, an average of 89% of hairs are in anagen, 10% in telogen, and 1% in catagen. A diagnosis of telogen effluvium is established when over 20% of the hairs examined are in telogen phase.
\nDystrophic hairs have a decreased proximal diameter, an irregular contour, no epithelial sheaths, and an angle of over 20. They are common in AGA or in hair that has not been removed correctly from the scalp. Keratotic material may be observed on the tip of the hair in conditions such as seborrheic dermatitis, psoriasis, and folliculitis. A common finding in patients with demodicosis is the presence of Demodicosis folliculorum in contact with the root of the hair, although this condition is usually diagnosed by superficial skin biopsy [99].
Normal hair is uniform in appearance and structure along the entire length of the hair shaft; this uniformity is also observed between the different hairs in a sample. Hair dysplasias are malformations of the hair shaft. Although scanning electron microscopy is the diagnostic tool of choice in such cases, certain signs may be observed in the trichogram [101]:
\n\nAlternating segments of narrowings and nodosities, giving a characteristic beaded appearance.
\nRound hairs with irregular, sporadic rounded nodosities. There are no narrowings.
Twists of hairs with bending at different angles and regular intervals.
Ball‐shaped deformity with cupping at the proximal end of the hair shaft.
Patients with trichothiodystrophy may have hair with ribbon‐like flattening, characteristic trichoschisis‐like fractures (clean transverse breaks), with an irregular surface, and tiger‐tail banding.
Single or double knots on the hair shaft. Tie knots and other more complex knots are also observed.
Bulging hair characterized by fracture nodes with open splitting of the cortex on both sides of the node. If the hair eventually splits, it will leave a brush‐like appearance at both ends.
Short, broken hairs with a wavy surface,and bubbles inside the shaft.
Twisted anagen hairs with a ruffled cuticle at the proximal end. Long, pili canaliculi type canals on the shaft are a common finding [102].
Hair shafts with alternating light and dark bands.
Thin curly hair forming small woolly balls.
Canalicular formation along the entire length of the hair shaft. This formation can be difficult to spot under a microscope but the micrometer can be moved if pili canaliculi is suspected.
Three types of hair shaft tips can be observed:
\nJavelin tip: A very sharp, spear‐like tip is seen in hair that is growing well and has never been cut, paintbrush tip: Fractures in the hair shaft (trichoschisis) give the tip a paintbrush‐like appearance, seen in hair shaft anomalies such as monilethrix, alopecia areata, or in hair fragility induced by cosmetic products an clean‐cut tip: The distal end has been cut and ends in a perfectly straight line. It is typically seen in hair that has been cut and in cases of trichotillomania [99].
In alopecia areata, hair shaft is with alternating narrow and normal sections. Pseudomonilethrix and/or trichoschisis may be observed in some hairs. Hair shaft diameter variability has been demonstrated in women, with larger diameters seen in higher stages of the Ludwig Scale [103]; the differences were minimal at stage I and maximal at stage III. In TE, the hairs are shorter than normal, have a uniform diameter, a rounded proximal end (club‐like appearance) and a lack of pigment and membranes. In anagen effluvium normal anagen hairs that are longer than telogen hairs, pigmented, and having sheaths and membranes whose distal end is angled like a golf club are seen in the trichogram. Nits or lice may be seen in patients with pediculosis capitis [99].
AA | alopecia areata |
AGA | androgenetic alopecia |
DLE | discoid lupus erythematosus |
FFA | frontal fibrosing alopecia |
LPP | lichen planopilaris |
TE | telogen effluvium |
WD | white dots |
YD | yellow dots |
The growth of cells in a controlled artificial environment isolated from their natural habitat is referred to as cell culture [1]. It is a significant tool used widely to study cell and molecular biology, screening drugs and toxicity analysis, the role of a particular gene in a disease, and cancer research. Due to their unique properties, they also have been tuned for screening and developing biopharmaceutical compounds such as vaccines and recombinant proteins. One of the major advantages of using cell culture is the homogenous and reproducible data generated [2].
Drug discovery is a lengthy and time-consuming process that undergoes several stages of testing and optimization. This encompasses identification of the target, lead discovery, pre-clinical validation, and clinical trials [3]. Therefore, it is very pertinent to obtain information about the biological activity, biochemical mechanisms, toxicity, and off-target interactions of drug molecules leading to the early stages of drug discovery.
Two-dimensional (2D) cell culture was introduced many decades ago that has been the major type of cell culture technique in numerous fields. This traditional approach has been extensively used for drug screening due to its relatively inexpensive feature and convenience to use. However, the issue of mimicking the
Simplified sketch of 2D cell culture (a) and 3D cell culture (b).
Recently there has been an upsurge of interest towards three-dimensional (3D) cell culture in biomedical research and drug development processes due to its high-throughput accuracy and refined
Cytotoxicity assays are commonly used for
Assays based on metabolism generally include the 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and its alternatives such as 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT),3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS) and sulforhodamine B (SRB) assay. Due to rapid, quantitative, versatile, and highly reproducibility of MTT, it is widely used in large-scale, anti-tumor drug-screening program. MTT is a quantitative colorimetric assay that quantifies the reduction of yellow tetrazolium dye by mitochondrial succinate dehydrogenase to purple insoluble formazan crystals by the NADPH dependent cellular oxidoreductase enzymes [12]. The crystals are dissolved in an appropriate solvent. The absorbance is then recorded using a spectrophotometer to analyze the cell viability wherein the crystals get accumulated in the viable cells due to their impermeability to the cell membrane.
ATP Bioluminescence Assay is used to measure the ATP level that is well regulated in the metabolically active live eukaryotic cells as compared to the dead cells wherein the ATP level falls due to the activity of ATPases. This assay includes a luciferase enzyme that utilizes energy from ATP that converts luciferin into oxyluciferin and thus produces luminescence. Therefore, luminescence could be used to measure the ATP level. Assays based on the release of enzymes are more significant as they measure the products released by the dead cells [13].
Assays based on the release of enzymes include Lactate dehydrogenase(LDH) leakage assay involving the formation of pyruvate from lactate in the presence of LDH with simultaneous reduction of NAD to NADH that alters the absorbance at 340 nm [14]. Research in cancer and cell biology is greatly dependent on
Cell migration is well known for its significant role in embryonic morphogenesis, cancer invasion and metastasis, immune responses, tissue formation, and angiogenesis [19]. Mainly, cell migration is of two types; single-cell migration and collective cell migration. Single-cell migration is regulated by cytoskeletal activity without cell-to-cell interactions with neighboring cells. This type of migration is important for embryonic development, immune response, and in the early stages of metastasis. On the other hand in the collective cell migration, the group of cells retains their cell to cell interactions as well as collective polarity. Wound healing assay or scratch assay is a 2D
Another assay involving the response of single cells to various chemo-attractants is the transwell assay or the Boyden Chamber assay. This assay can be used for both adherent and non-adherent cells wherein the cells are placed in a serum-free medium on one side of a porous membrane and analyzed on the basis of the cell’s ability to migrate through the pores to the other side. Cell migration can be quantified by counting the cells that have traversed through the membrane towards the higher concentration of chemoattractant [21]. A drawback of this assay is visualizing the cells and their morphology while migrating through pores due to the transitive state of cells [22].
Cancer is one of the most frightful diseases in both developing and developed countries and imparts a major health burden to the society. Tumorigenicity is the tendency of the cultured cells to form tumors. The two common
Colony forming assay is performed using the soft agar method. The basic steps involved in this assay are treating the cell monolayer in the flask, seeding the required number of cells on the agar and incubate for 1–3 weeks, fixing and staining the colonies and finally observing the colonies under the stereomicroscope [23]. Another
Cell migration is an important process in biology where the cells changes and reaches their destination within a proper environment, in order to execute their respective function. It is a normal physiological process that takes place in nearly all forms of organisms. However, changes or deregulation of any kind in the pattern of cell migration or invasion are an indication of pathological conditions including inflammatory diseases and cancer metastasis, with the latter being the most explored one [21]. There are various biological methods that are commonly employed in the scientific community to study the above-mentioned events in depth namely, the cell culture wound-healing assay, the transwell migration, and invasion assay, individual cell-tracking assay, and spreading assay. These assays aim to provide relevant information pertaining to the pattern of cell migration or its response to chemoattractant(s).
It is the simplest of all methods in determining the migration of whole-cell masses altogether. Going further in detail, it can be used to interpret individual cell’s morphological characteristics and phenotypes during migration. Measuring the closed distance compared to the control over regular intervals of time shows specific migration changes or phenotype that was unknown in the past [26].
The transwell migration and invasion assay are used to determine the capability of single cells to respond to various chemoattractant(s) including chemokines, growth factors, lipids, or nucleotides. It also contributes to assessing differential cell migration due to the over-expression of a receptor. It also identifies and characterizes the key regulators participating in cell migration [26].
Conducting single-cell tracking and its live imaging under appropriate conditions adds to the overall advantage of cell migration assay. The software includes a time-lapse video-microscopy protocol comprising of post-processing tracks of the cell populations with single-cell resolution. It greatly helps to understand the cell biology and lineage progression of distinct cell populations [27].
In this type of assay, the spreading process of individual cells is seen and recorded with the help of Differential Interference Contrast microscopy (DIC). The spreading state is recorded every 5 seconds with a Charge-Coupled Device (CCD) of the camera, producing high-quality grayscale images. The process of taking images could extend to several hours [28].
Antibodies, one of the major elements of the immune system are the glycoproteins produced by the immunoglobulins; B-cells provide protection against invading pathogens. The antibodies are highly specific and selective, thus have been used as an extraordinary tool in bioengineering and biomedical research for many years. The antibodies are majorly classified into two categories, Monoclonal Antibodies (mAbs) and Polyclonal Antibodies (pAbs) are based on their origin from the lymphocytes. mAbs are produced by only B lymphocyte or B cells and are monospecific. Due to this property, they possess high specificity and affinity towards a single epitope of an antigen whereas pAbs are produced by different B-cells and possess different affinities for multiple epitopes of a specific antigen. Since mAbs are highly specific, they are produced on a large scale through culturing of antibodies-producing cells widely known as ‘Hybridomas’, which are commonly derived from mice, and the method is known as ‘Hybridoma Technology [29].
Hybridoma technology was discovered and developed by two eminent scientists, Georges Kohler and Cesar Milstein in 1975 and is considered to be one of the biggest breakthroughs. It has proved to be a robust, effective, and successful methodology employed in the field of biotechnology and biomedical research that solely deals with mAb isolation. The B cells go through the antibody maturation process in the germinal centers of secondary lymphoid tissues (for example, lymph nodes, spleen, tonsils, and Peyer’s patches). Upon proliferation, certain mutations are experienced by the B cells, specifically in the genes encoding the variable region of the antibodies that helps in the selection for high-affinity tight binding to the corresponding antigen. The overall resulting antibodies by B cells consist of a natural pairing of the light chain and variable heavy chain genes with constant region genes. This region contains Class Switch Recombination (CSR) differentiates from the hybridoma technology in which CSR is absent [29].
Following are the steps employed for the production of monoclonal antibody by hybridoma technology.
The mouse/mice is/are immunized every 2–3 weeks with red blood cells taken from sheep in order to produce the B cells. These antibodies are isolated from the spleen cells of mice.
After the process of immunization, the blood samples are taken from the mouse to determine the serum antibody titer. When the titer reaches the optimal level, the mouse is boosted by injecting antigen 3 days prior to fusion with myeloma cells [30].
Fusion of isolated spleen cells (limited life span) with tumor lymphocytes (immortal) with the help of PEG (Polyethylene Glycol) leads to the development of hybridomas with an unlimited life span.
Hybridomas are grown in a selective medium containing Hypoxanthine, Aminopterin and Thymidine (HAT). Aminopterin present in the media blocks pathway for nucleotide synthesis, making the cells dependent on the alternative pathway which is not evident in myeloma cells.
The cells are screened and chosen or selected for production of antibodies with the desired specificity.
The cells are cultured and used for the production of large quantities of antibodies [31].
The cells are frozen and stored for future use in therapeutics.
Gene, the fundamental biological unit of heredity that constitutes an ordered sequence of nucleotides present in chromosomes. The functional aspect of a gene is to encode a protein or RNA molecule inherited from parents such as texture and color of the hair and eyes. Any kind of alterations/mutations in a gene sequence can lead to abnormal functionality of the genes. Gene therapy is a modern type of experimental technique in the medical field which involves rectifying the non-functional or malfunctioning of genes by replacing them with healthy and functional genes. Several approaches have been implemented by researchers in terms of correcting a mutated gene with a healthy copy of the gene or by inactivating the mutated gene causing disease. It has been widely studied for various diseases such as immune deficiency, blood disorders, eye problems, metabolic disorders, regeneration of nerve cells, and cancer [32]. The first case of gene therapy was discovered in the 1990s whereby a functional Adenosine Deaminase (ADA) gene was incorporated in the white blood cells of the patient, replacing the non-functional ADA [33]. This application led to interesting results with the immune systems and hence, was considered the most reliable technique.
There are two main methods for gene therapy such as-
The strategy of gene therapy has been applied to this disease in order to improve the advanced symptoms of PD. Gene therapy was applied to transfer ‘Glutamic Acid Decarboxylase (GAD), a chemical produced by a gene into the basal ganglia. GAD showed an increased amount of a neurotransmitter called as Gamma-Aminobutyric Acid (GABA), responsible for inhibiting brain signals and decreasing activity in the nervous system Decreased GABA activity leads to certain brain-related disorders [34].
AD and other frontotemporal dementias (FTDs) are caused by the accumulation of amyloid-β peptide (Aβ) and protein tau in the brain. It is characterized by having memory loss, difficulty in learning and communicating along with the inability to organize things. The use of recombinant Adeno-Associated Viruses (rAAVs) has provided new ways for studying AD and other related neurological disorders [35]. Such strategies or approaches have added novel dimensions to medical treatments.
Cystic fibrosis is a disease known to affect the lungs primarily. Its symptoms include inflammation, airway obstruction leading to respiratory tract infection and deformity. Insertion of the Cystic Fibrosis Transmembrane Regulator (CFTR) gene directly into the epithelium cells of the respiratory tract bear the capability to lessen the symptoms but not totally cure the disease in patients suffering from cystic fibrosis [36].
Cell-based therapy is one of the most important and well-known forms of all treatments in the fields of modern science & medicine. It is not only a curative option for treating deadly or threatening diseases but is also making ‘Regenerative Medicine’ the most vital technique in health care with the specific goal of replacing diseased cells, tissues or organs and thereby restoring their normal function(s) [4]. Over the years, there has been a gush of interests and work done in understanding the potential of stem cells. They are the cells found naturally in the living bodies, characterized by two defining properties of eternal self-renewal and the propensity to differentiate into an adult cell type. There are three main types of stem cells: Totipotent (a cell developing into a healthy organism independent of the permissive environment), Pluripotent (a cell developing into any type of adult cell) and Multipotent (a cell developing into a limited type of cell) [37].
Following is the account of different stem cells used for the treatment of various diseases:-
Reportedly, pluripotent cells have been used successfully to treat animals per se. Animals diagnosed with diabetes are incorporated with cells containing insulin responsive to glucose levels. Additionally, the treatment of the animals suffering from acute spinal cord injury and visual impairment is performed with myelinated neurons and retinal epithelial cells, respectively. Researchers are still conducting studies with the use of pluripotent stem cells to cure several disorders such as Parkinson’s disease, muscular dystrophy and heart failure.
The stem cells created artificially from normal adult somatic cells through co-expression of genes and factors are known as Induced Pluripotent Stem Cells (iPSCs). These are important for maintaining the characteristic properties of Embryonic Stem (ES) cells. Some reports have stated the successful use of iPSCs in conditions like Parkinson’s disease, spinal muscular atrophy, cardiac diseases, blood disorders, diabetes, amyotrophic lateral sclerosis, Huntington’s disease, and familial dysautonomia.
The multipotent stem cells derived from bone marrow (Hematopoietic stem cells) have been used in the 1960s to treat cancer conditions like leukemia, myeloma and lymphoma. Mesenchymal stem cells with the capability of forming whole joints in mouse models have been used regenerating bone and cartilages form. Curing heart ailments are still under clinical trial.
Spurred by the recent advent in cell culture technologies, three-dimensional (3D) cell culture is paving the way in promoting tissue organization and cell differentiation by triggering tissue-based diseased microenvironment. An ideal 3D cell culture system generally composed of tightly bound tissues that involve cell–cell fluent interaction almost mimicking the extracellular matrix (ECM) that is highly dynamic and includes scaffolds of cells in a fluid that enhances them to differentiate (Table 1). The key parameter of a 3D culture environment is the ability to organize the spatial arrangement of cells with other surrounding cells along with physical constraints [8]. This significant approach has gardened great focus on understanding complex cellular biology and their responses by validating mammalian tissue studies via linking the gap between
Approach | Merits | Demerits |
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3D Spheroids |
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Hydrogels |
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Organoids |
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Cancer co-culture Models |
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Organ-on-a-chip |
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Merits and demerits of different 3D cell culture techniques.
Organ type | Incorporated cell types | Organ-specific properties | Ref. |
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Lung | Primary lung alveolar epithelial cells |
| [76, 77] |
Primary lung endothelial cells |
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Human vascular endothelial cells |
| [78] | |
Human alveolar epithelial cells | |||
Skin | Peripheral perfusion fluid (PPF) |
| [79] |
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Liver | Hepatic cell lines |
| [80] |
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Kidney | Human podocytes Glomerular endothelial cells |
| [81] |
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Human-derived renal proximal tubule epithelial cells |
| [82] | |
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Heart | Cardiomyocytes |
| [83, 84] |
Pancreas | Human pancreatic beta-cell line |
| [85] |
Summary of recent organ-on-a-chip models.
3Dspheroids or multi-cellular aggregates are spherical micro-sized cellular constructs that are produced from numerous gamuts of cell types, originally from scaffold-free systems. The most characteristic features of 3D spheroids are the ability to recapitulate a cell’s typical physiological behavior, cellular heterogeneity, gene expression, cell–cell signaling, and structural architecture with respect to cell–cell contact [10]. Various types of 3Dspheroids include embryonic bodies, tumor spheroids (spheres of different tumorcells), hepatospheres (spheres of hepatic cells), neurospheres (spheres of different cell types of the central nervous system (CNS)) and mammospheres (spheres of mammary glands) [38]. An ideal 3D spheroid constitute ECM components such as proteoglycans, laminin, collagen, fibronectin, tenascin, and glycosaminoglycans [39] which tightens the spheroid density with close ECM-cell and cell–cell anchors eventually increase interstitial fluid pressure (IFP). Depending on the primary amount of cells seeded, the size of spheroid increases with an elevation in cell number, oxygen, and nutrient gradients equivalent to the tissue of interest [5]. Alongside, the different techniques enabling spheroid cultures are illustrated further.
Hanging drop technique is a non-scaffold method wherein a drop of media containing cells are suspended inversely on the lid of the culture dish (bottom-less and open) such that there is no surface provided for the cells and tend to hang. This attempt forms a cluster called spheroid at the tip of the droplet when cultured for a longer period [40]. Spheroids formed through hanging drop cultures have fetched considerable stance in cell culture technology with 100% reproducibility owing to ubiquitous applications in cancer research [41], toxicity testing in hepatocytes [42], and constructing cardiac spheroids [43]. Another method involves the use of a liquid overlay that eases the formation of aggregates and commercially produced as low adhesion plates. These spheroid microplates contain either hydrophilic or hydrophobic coating with V-shaped bottom and allow mild attachment to the surface such that the cells tend to self-aggregate and form spheroid. Unlike the hanging drop technique, low adhesion plates generate one spheroid per plate that signifies its importance for multicellular culture. This ensures a medium-throughput screening that requires no modification in spheroid formation [44]. Spheroids can also be cultured with the use of magnetic nanoparticles with the application of the magnetic field. The process is called magnetic cell levitation that is highly applied to produce spheroids of mesenchymal stem cells and tissue engineering [45, 46]. An
Organoids refer to the primary cultures derived from cell aggregates through
Cancer cell lines have emerged as an eminent tool for comprehending complex physiology of cancers. The cell cultures have eased the outlook in preclinical research to understand the process of disease, morphological changes occurring in tissue, gene function, cell biology and tissue engineering [58]. They have evolved with immense features of offering homogenous samples without any sort of modification and variations. However, a big leap was noted when monolayer cell cultures (2D) obtained from solid tumors were incapable of mimicking the structural elements of tumor microenvironment. Thusly, 3D cancer cell culture models have placed an enduring platform recently whereby ECM in 3D construct is same as that of original cell culture and imparted knowledge of predicting tumor response to treatment [59]. The application of 3D cell culture models of tumors have ought to manifest typical properties of tumor microenvironment such as gene and protein expressions, morphology, angiogenesis, malignancy and invasiveness. From this standpoint, 3D tumor cell culture models scintillate anticancer therapeutics and cancer drug discovery. To date, a vast content of literature owes the significance of these 3D co-cultures models in varying applications. In a study, tumor-associated macrophages (TAM) or cancer-associated fibroblasts (CAF) and gelatin hydrogel microspheres (GM) have been applied to produce cancer co-culture models from different cancer cells including HepG2 (liver), MCF-7 (breast) and WA-hT (lung) in order to inspect sustained release of drugs. They induced metastatic proteins involved in epithelial-mesenchymal transition (EMT) with transforming growth factor-β1 (TGF-β1) and reported elevation in N-cadherin and Vimentin proteins with deceleration in E-cadherin protein [58]. Recently, cancer co-culture models evinced interest in numerous approaches such as 3D breast cancer co-culture models obtained from MCF-7, MRC-5 and MDA-MB-231 tumor cells were used in investigating radiation-induced fibrosis [59], tumor-associated fibroblast differentiation [60] and development of immunotherapies [61], 3D lung cancer co-culture models derived lung squamous carcinoma and Non-Small Cell Lung Cancer Cells (NSCLC)fromTUM622, A549 and Colo699 tumor cells were utilized to explore tumor-stroma interactions [62, 63], 3D renal cancer co-culture models formed from Caki 1 (skin metastasis derived) and ACHN (pleural effusion derived) were sought for determining the efficacy of produced 3D models in stem cell physiology research and drug toxicity screening [64]. 3D colon cancer co-culture models acquired from LS 174 T, HCT 116, Colo205, MCF7, SW480, SW620, CCD-18Co, Caco-2, HT-29, and H446 have also been used to explore tumor-stroma interactions [65].
Organ-on-a-chip is a biomimetic system that uses fabrication of computerized microchips and microfluids consisting of living cells, mimicking the natural environment of organs from which it is been created. There are several factors that made organ chips be listed in “Top Ten Emerging Technologies” in the World Economic Forum [75] such as shear force, tissue-boundaries, concentration gradients, tissue–organ interactions and cell patterning. Organ chips have intensified in the field of drug therapeutics for their ability of high throughput screening. Table 2 summarizes the recent researches carried out using various organ chips. These organ chips use microtechnology that provides nutrients to the cells for their better growth and proliferation. Microfluids are one such component that has been used in various studies for efficient treatment in drug sensitivity testing [86]. Talking of this notion, a microfluidic chip was produced in order to monitor and document real-time impedimetric biosensor changes. Other organ-on-a-chip models such as blood–brain barrier chips have been developed to represent the
Animal models used in laboratories have been greatly avoided due to the fact that they are costly and require a large number of laborers. This approach was replaced by the use of
Drug discovery is a lengthy and time-consuming process that undergoes several stages of testing and optimization. This encompasses identification of the target, lead discovery, pre-clinical validation, and clinical trials [3]. Due to the constant failure of drugs in Phase II and Phase III clinical trials, there has been constant pressure on the pharmaceutical industry to seek more novel drugs with lower side effects and cost-effectiveness. 3D cell culture has emerged as a significant high-throughput system that has uplifted the standards of cell culture [93]. Specifically, spheroids are considered the most reliable model for testing drugs in various diseases because of their capability of resembling the natural environment of original tissue [93]. The spatial organization of spheroids in different layers of cells leads to cellular death by forming reactive oxygen species [94]. In the case of investigating the effect in 3D spheroids, fluorescence microscopy plays a key role in determining pharmaceutical dispersion within spheroids (eg-doxorubicin and epirubicin) [95]. The capital importance of any drug testing involves cell-based assays that are efficient enough and easily reproducible compared to expensive animal models. Cell-based assays have shaped the physiological relevance of 2D cultures [96]. While the reaction may vary from technique to technique such as cell viability, proliferation, signaling and migration and drug to drug for achieving better sensitivity. It is now broadly accepted that compared to 2D cultures, 3D models serve the resemblance of the natural environment of original tissue efficiently and differently in 3D environments. Research has nested stance on novel 3D culture technologies that impart functional basis of tissues such as spheroids and organoids [97]. A study used 3D hydrogel-based model for the determination of drug sensitivity in HepG2 cell lines by comparing cytotoxicity effect with cytotoxicity (CT50) and lethal dose (LD50) values [98]. Organoid 3D models also aid as a resourceful tool for modeling neurodevelopmental disorders [98]. Microfluidic chips have also been utilized in drug sensitivity testing whereby a study elaborated its efficacy in lung cancer which was in combination with stromal cell lines [98]. Evaluation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the drug is primarily examined in
Therapeutic proteins production using human cell lines has greatly influenced different medical areas including biopharmaceutical research and vaccine production. Mammalian cell lines prove futile in protein production due to their likelihood of possessing post-translational modifications (PTMs) achieved from recombinant proteins that are in accordance with the endogenous human proteins. These cell lines show exquisite specificity to produce similar proteins to those in humans naturally synthesized, an advantage over mammalian expression systems [99]. One of the most routinely and high yields of proteins production is performed by using cell-based expression systems such as Chinese hamster ovary (CHO) a cell line that constitutes major advances such as accomplishment of gene amplification, specific productivity, better selection strategies, and devising greater expression units and advanced hosts. CHO cells have established their safety profile for 20 years from the production of its first recombinant biotherapeutic protein in 1986 [100]. Other human cell lines such as BHK-21 cells are used for the generation of few coagulation factors such as factor VIII [101]. There are two vital human cell lines namely, HEK293 and HT-1080 that are used to manufacture licensed products of human PTMs. The advancement in protein-based drug development and technologies has driven more towards the therapeutic proteins market that comprises of sales of these therapeutic proteins. The methods that are involved in the production of these proteins are pegylation, glycoengineering, albumin fusion, Fc-fusion, product purity, targeting, and functionality of therapeutic protein drugs. Few examples of therapeutic protein drugs which has been produced using protein engineering technologies and approved by the Food and Drug Administration (FDA) from the past five years are imiglucerase, Belimumab, alfa, coagulation factor IX recombinant human and albiglutide [102]. A French pharmaceutical company named Sanofi accomplished a great achievement of strengthening its R&D strategy with the best proprietary therapeutic proteins production pharmaceutical company, Ablynx, for a nanobody technology platform.
In particular, a plethora of research studies have shed light on the fact that in spite of the availability of advanced organ-on-chip technologies and bioengineered 3D models, the application is limited by drug companies due to their relatively novel approach which is more likely requires to undergo further validation and characterization. Moreover, 3D cell culture models with high-throughput screening in combination with high-content leads to the identification of clinically relevant compounds. However, still many difficulties are being faced as 3D cell cultures do not meet certain criteria in the drug discovery process with regard to size, morphology, complexity, and protocol for assaying. It requires ample standardization and optimization to extract successful specific phenotypes for drug screening. Thus, there are few 3D models that are constrained for their restricted access due to limited permeability. Following the advances in protein therapeutics, more improvements in generating sophisticated therapeutic protein products will be developed for better futuristic research.
Authors thanks, Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Tathawade, Pune, for providing necessary facilities. This work was supported by Dr. D. Y. Patil Vidyapeeth seed grant (DPU/14/2016, dated 06/01/2016).
There are no conflicts of interest.
2D | Two-dimensional |
3D | Three-dimensional culture |
Aβ | Amyloid-β peptide |
ADMET | Absorption, distribution, metabolism, excretion and toxicity |
ADA | Adenosine Deaminase |
AD | Alzheimer’s disease |
ARDS | Acute respiratory disease syndrome |
CAF | Cancer-associated fibroblasts |
CCD | Charge-Coupled Device |
CFTR | Cystic fibrosis transmembrane regulator |
CHO | Chinese hamster ovary |
CNS | Central nervous system |
CSCs | Cancer stem cells |
CT50 | Cytotoxicity 50 percent |
CSR | Class Switch Recombination |
DIC | Differential Interference Contrast microscopy |
ECM | Extracellular matrix |
ES | Embryonic Stem |
EMT | Epithelial-mesenchymal transition |
FTDs | Frontotemporal dementias |
GABA | Gamma-Aminobutyric Acid |
GAD | Glutamic Acid Decarboxylase |
GM | Gelatin hydrogel microspheres |
HAT | Hypoxanthine, Aminopterin, Thymidine |
IFP | Interstitial fluid pressure |
iPSCs | Induced pluripotent stem cells |
LDH | Lactate dehydrogenase |
LD50 | Lethal dose 50 percent |
MTT | 3-(4,5-dimethythiazol2-yl)-2,5-diphenyl tetrazolium bromide |
MTS | 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium |
MDC | Microfluidic Diffusion Chamber |
mAbs | Monoclonal Antibodies |
NAD | Nicotinamide adenine dinucleotide |
NADH | Reduced nicotinamide adenine dinucleotide |
NADPH | Nicotinamide adenine dinucleotide phosphate |
NSCLC | Non-Small Cell Lung Cancer Cells |
pAbs | Polyclonal Antibodies |
PDX | Patient-derived xenograft |
PD | Parkinson’s Disease |
PPF | Peripheral perfusion fluid |
PTMs | Post-translational modifications |
rAAVs | Adeno-Associated Viruses |
SRB | Sulforhodamine B |
TAM | Tumor-associated macrophages |
TGF-β1 | Transforming growth factor-β1 |
TME | Tumor microenvironment |
XTT | 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide. |
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Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\r\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\r\nHer topics of interest are biomaterials science and cell culture studies. She has many articles in international and national scientific journals and chapters in books; she also has participated in several scientific projects supported by Istanbul University Research fund.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Orthodontist, Assoc Prof in the Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"260116",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yaltirik",slug:"mehmet-yaltirik",fullName:"Mehmet Yaltirik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/260116/images/7413_n.jpg",biography:"Birth Date 25.09.1965\r\nBirth Place Adana- Turkey\r\nSex Male\r\nMarrial Status Bachelor\r\nDriving License Acquired\r\nMother Tongue Turkish\r\n\r\nAddress:\r\nWork:University of Istanbul,Faculty of Dentistry, Department of Oral Surgery and Oral Medicine 34093 Capa,Istanbul- TURKIYE",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/172009/images/7122_n.jpg",biography:"Dr. Deniz Uzuner was born in 1969 in Kocaeli-TURKEY. After graduating from TED Ankara College in 1986, she attended the Hacettepe University, Faculty of Dentistry in Ankara. \nIn 1993 she attended the Gazi University, Faculty of Dentistry, Department of Orthodontics for her PhD education. After finishing the PhD education, she worked as orthodontist in Ankara Dental Hospital under the Turkish Government, Ministry of Health and in a special Orthodontic Clinic till 2011. Between 2011 and 2016, Dr. Deniz Uzuner worked as a specialist in the Department of Orthodontics, Faculty of Dentistry, Gazi University in Ankara/Turkey. In 2016, she was appointed associate professor. Dr. Deniz Uzuner has authored 23 Journal Papers, 3 Book Chapters and has had 39 oral/poster presentations. She is a member of the Turkish Orthodontic Society. Her knowledge of English is at an advanced level.",institutionString:null,institution:null},{id:"332914",title:"Dr.",name:"Muhammad Saad",middleName:null,surname:"Shaikh",slug:"muhammad-saad-shaikh",fullName:"Muhammad Saad Shaikh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jinnah Sindh Medical University",country:{name:"Pakistan"}}},{id:"315775",title:"Dr.",name:"Feng",middleName:null,surname:"Luo",slug:"feng-luo",fullName:"Feng Luo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sichuan University",country:{name:"China"}}},{id:"344229",title:"Dr.",name:"Sankeshan",middleName:null,surname:"Padayachee",slug:"sankeshan-padayachee",fullName:"Sankeshan Padayachee",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"315727",title:"Ms.",name:"Kelebogile A.",middleName:null,surname:"Mothupi",slug:"kelebogile-a.-mothupi",fullName:"Kelebogile A. Mothupi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"423519",title:"Dr.",name:"Sizakele",middleName:null,surname:"Ngwenya",slug:"sizakele-ngwenya",fullName:"Sizakele Ngwenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"337613",title:"Mrs.",name:"Tshakane",middleName:null,surname:"R.M.D. Ralephenya",slug:"tshakane-r.m.d.-ralephenya",fullName:"Tshakane R.M.D. Ralephenya",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"419270",title:"Dr.",name:"Ann",middleName:null,surname:"Chianchitlert",slug:"ann-chianchitlert",fullName:"Ann Chianchitlert",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419271",title:"Dr.",name:"Diane",middleName:null,surname:"Selvido",slug:"diane-selvido",fullName:"Diane Selvido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}},{id:"419272",title:"Dr.",name:"Irin",middleName:null,surname:"Sirisoontorn",slug:"irin-sirisoontorn",fullName:"Irin Sirisoontorn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Walailak University",country:{name:"Thailand"}}}]}},subseries:{item:{id:"23",type:"subseries",title:"Computational Neuroscience",keywords:"Single-Neuron Modeling, Sensory Processing, Motor Control, Memory and Synaptic Pasticity, Attention, Identification, Categorization, Discrimination, Learning, Development, Axonal Patterning and Guidance, Neural Architecture, Behaviours and Dynamics of Networks, Cognition and the Neuroscientific Basis of Consciousness",scope:"Computational neuroscience focuses on biologically realistic abstractions and models validated and solved through computational simulations to understand principles for the development, structure, physiology, and ability of the nervous system. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",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.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"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",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",fullName:"Johann F. 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