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Tissue engineering
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=== Materials === Material selection is an essential aspect of producing a scaffold. The materials utilized can be natural or synthetic and can be biodegradable or non-biodegradable. Additionally, they must be biocompatible, meaning that they do not cause any adverse effects to cells.<ref>{{cite book|title=Frontiers in tissue engineering|date=1998|publisher=Pergamon| vauthors = Patrick CW, Mikos AG, McIntire LV |author3-link= Larry McIntire |isbn=978-0-08-042689-1 |edition=1st|location=Oxford, UK|oclc=162130841}}</ref> Silicone, for example, is a synthetic, non-biodegradable material commonly used as a drug delivery material,<ref>{{cite journal | vauthors = Stewart SA, Domínguez-Robles J, Donnelly RF, Larrañeta E | title = Implantable Polymeric Drug Delivery Devices: Classification, Manufacture, Materials, and Clinical Applications | journal = Polymers | volume = 10 | issue = 12 | pages = 1379 | date = December 2018 | pmid = 30961303 | pmc = 6401754 | doi = 10.3390/polym10121379 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kajihara M, Sugie T, Maeda H, Sano A, Fujioka K, Urabe Y, Tanihara M, Imanishi Y | display-authors = 6 | title = Novel drug delivery device using silicone: controlled release of insoluble drugs or two kinds of water-soluble drugs | journal = Chemical & Pharmaceutical Bulletin | volume = 51 | issue = 1 | pages = 15–19 | date = January 2003 | pmid = 12520121 | doi = 10.1248/cpb.51.15 | doi-access = free }}</ref> while gelatin is a biodegradable, natural material commonly used in cell-culture scaffolds<ref>{{cite journal | vauthors = Afewerki S, Sheikhi A, Kannan S, Ahadian S, Khademhosseini A | title = Gelatin-polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics | journal = Bioengineering & Translational Medicine | volume = 4 | issue = 1 | pages = 96–115 | date = January 2019 | pmid = 30680322 | pmc = 6336672 | doi = 10.1002/btm2.10124 }}</ref><ref>{{cite journal| vauthors = Martin CA, Radhakrishnan S, Nagarajan S, Muthukoori S, Dueñas JM, Ribelles JL, Lakshmi BS, Nivethaa EA, Gómez-Tejedor JA, Reddy MS, Sellathamby S | display-authors = 6 |date=2019|title=An innovative bioresorbable gelatin based 3D scaffold that maintains the stemness of adipose tissue derived stem cells and the plasticity of differentiated neurons|journal=RSC Advances|language=en|volume=9|issue=25|pages=14452–64|doi=10.1039/C8RA09688K| pmid = 35519343 | pmc = 9064131 | bibcode = 2019RSCAd...914452M |issn=2046-2069|doi-access=free}}</ref><ref>{{cite journal| vauthors = Takagi Y, Tanaka S, Tomita S, Akiyama S, Maki Y, Yamamoto T, Uehara M, Dobashi T |date=2017|title=Preparation of gelatin scaffold and fibroblast cell culture |journal=Journal of Biorheology |volume=31|issue=1|pages=2–5|doi=10.17106/jbr.31.2|issn=1867-0466|doi-access=free |url=https://www.jstage.jst.go.jp/article/jbr/31/1/31_2/_article}}</ref> The material needed for each application is different, and dependent on the desired mechanical properties of the material. Tissue engineering of long bone defects for example, will require a rigid scaffold with a compressive strength similar to that of cortical bone (100-150 MPa), which is much higher compared to a scaffold for skin regeneration.<ref>{{cite journal | vauthors = Roohani-Esfahani SI, Newman P, Zreiqat H | title = Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects | journal = Scientific Reports | volume = 6 | issue = 1 | pages = 19468 | date = January 2016 | pmid = 26782020 | pmc = 4726111 | doi = 10.1038/srep19468 | bibcode = 2016NatSR...619468R }}</ref><ref>{{cite journal | vauthors = Nokoorani YD, Shamloo A, Bahadoran M, Moravvej H | title = Fabrication and characterization of scaffolds containing different amounts of allantoin for skin tissue engineering | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 16164 | date = August 2021 | pmid = 34373593 | pmc = 8352935 | doi = 10.1038/s41598-021-95763-4 | bibcode = 2021NatSR..1116164N }}</ref> There are a few versatile synthetic materials used for many different scaffold applications. One of these commonly used materials is polylactic acid (PLA), a synthetic polymer. [[Polylactide|PLA]] – polylactic acid. This is a polyester which degrades within the human body to form [[lactic acid]], a naturally occurring chemical which is easily removed from the body. Similar materials are [[Polyglycolide|polyglycolic acid]] (PGA) and [[polycaprolactone]] (PCL): their degradation mechanism is similar to that of PLA, but PCL degrades slower and PGA degrades faster.{{citation needed|date=December 2020}} PLA is commonly combined with PGA to create poly-lactic-co-glycolic acid (PLGA). This is especially useful because the degradation of PLGA can be tailored by altering the weight percentages of PLA and PGA: More PLA – slower degradation, more PGA – faster degradation. This tunability, along with its biocompatibility, makes it an extremely useful material for scaffold creation.<ref>{{cite journal | vauthors = Gentile P, Chiono V, Carmagnola I, Hatton PV | title = An overview of poly(lactic-co-glycolic) acid (PLGA)-based biomaterials for bone tissue engineering | journal = International Journal of Molecular Sciences | volume = 15 | issue = 3 | pages = 3640–59 | date = February 2014 | pmid = 24590126 | pmc = 3975359 | doi = 10.3390/ijms15033640 | doi-access = free }}</ref> Scaffolds may also be constructed from natural materials: in particular different derivatives of the [[extracellular matrix]] have been studied to evaluate their ability to support cell growth. Protein based materials – such as collagen, or [[fibrin]], and polysaccharidic materials- like [[chitosan]]<ref>{{cite journal | vauthors = Park JH, Schwartz Z, Olivares-Navarrete R, Boyan BD, Tannenbaum R | title = Enhancement of surface wettability via the modification of microtextured titanium implant surfaces with polyelectrolytes | journal = Langmuir | volume = 27 | issue = 10 | pages = 5976–85 | date = May 2011 | pmid = 21513319 | pmc = 4287413 | doi = 10.1021/la2000415 }}</ref> or [[glycosaminoglycan]]s (GAGs), have all proved suitable in terms of cell compatibility. Among GAGs, [[Hyaluronan|hyaluronic acid]], possibly in combination with cross linking agents (e.g. [[glutaraldehyde]], [[Ethyl(dimethylaminopropyl) carbodiimide|water-soluble carbodiimide]], etc.), is one of the possible choices as scaffold material. Due to the covalent attachment of thiol groups to these polymers, they can crosslink via disulfide bond formation.<ref>{{cite journal | vauthors = Leichner C, Jelkmann M, Bernkop-Schnürch A | title = Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature | journal = Advanced Drug Delivery Reviews | volume = 151-152 | pages = 191–221 | date = 2019 | pmid = 31028759 | doi = 10.1016/j.addr.2019.04.007 | s2cid = 135464452 }}</ref> The use of thiolated polymers ([[thiomer]]s) as scaffold material for tissue engineering was initially introduced at the 4th Central European Symposium on Pharmaceutical Technology in [[Vienna]] 2001.<ref>{{cite journal | vauthors = Kast CE, Frick W, Losert U, Bernkop-Schnürch A | title = Chitosan-thioglycolic acid conjugate: a new scaffold material for tissue engineering? | journal = International Journal of Pharmaceutics | volume = 256 | issue = 1–2 | pages = 183–189 | date = April 2003 | pmid = 12695025 | doi = 10.1016/S0378-5173(03)00076-0 }}</ref> As thiomers are biocompatible, exhibit cellular mimicking properties and efficiently support proliferation and differentiation of various cell types, they are extensively used as scaffolds for tissue engineering.<ref>{{cite journal | vauthors = Bae IH, Jeong BC, Kook MS, Kim SH, Koh JT | title = Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for osteogenic differentiation and ectopic bone formation | journal = BioMed Research International | volume = 2013 | pages = 878930 | date = 2013 | pmid = 24024213 | pmc = 3760211 | doi = 10.1155/2013/878930 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Bian S, He M, Sui J, Cai H, Sun Y, Liang J, Fan Y, Zhang X | display-authors = 6 | title = The self-crosslinking smart hyaluronic acid hydrogels as injectable three-dimensional scaffolds for cells culture | journal = Colloids and Surfaces B: Biointerfaces | volume = 140 | pages = 392–402 | date = April 2016 | pmid = 26780252 | doi = 10.1016/j.colsurfb.2016.01.008 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Gajendiran M, Rhee JS, Kim K | title = Recent Developments in Thiolated Polymeric Hydrogels for Tissue Engineering Applications | journal = Tissue Engineering. Part B, Reviews | volume = 24 | issue = 1 | pages = 66–74 | date = February 2018 | pmid = 28726576 | doi = 10.1089/ten.TEB.2016.0442 }}</ref> Furthermore thiomers such as thiolated hyaluronic acid<ref>{{cite journal | vauthors = Bauer C, Jeyakumar V, Niculescu-Morzsa E, Kern D, Nehrer S | title = Hyaluronan thiomer gel/matrix mediated healing of articular cartilage defects in New Zealand White rabbits-a pilot study | journal = Journal of Experimental Orthopaedics | volume = 4 | issue = 1 | pages = 14 | date = December 2017 | pmid = 28470629 | pmc = 5415448 | doi = 10.1186/s40634-017-0089-1 | doi-access = free }}</ref> and thiolated [[chitosan]]<ref>{{cite journal | vauthors = Zahir-Jouzdani F, Mahbod M, Soleimani M, Vakhshiteh F, Arefian E, Shahosseini S, Dinarvand R, Atyabi F | display-authors = 6 | title = Chitosan and thiolated chitosan: Novel therapeutic approach for preventing corneal haze after chemical injuries | journal = Carbohydrate Polymers | volume = 179 | pages = 42–49 | date = January 2018 | pmid = 29111069 | doi = 10.1016/j.carbpol.2017.09.062 }}</ref> were shown to exhibit [[wound healing]] properties and are subject of numerous [[clinical trials]].<ref>{{Cite web|url=https://www.uibk.ac.at/pharmazie/phtech/drugdelivery/neue-bilder-2022/studies-in-humans---clinical-trials.pdf|title=Studies in humans clinical trials}}</ref> Additionally, a fragment of an extracellular matrix protein, such as the [[Arginylglycylaspartic acid|RGD peptide]], can be coupled to a non-bioactive material to promote cell attachment.<ref>{{cite journal | vauthors = Pomeroy JE, Helfer A, Bursac N | title = Biomaterializing the promise of cardiac tissue engineering | journal = Biotechnology Advances | volume = 42 | pages = 107353 | date = 2020-09-01 | pmid = 30794878 | pmc = 6702110 | doi = 10.1016/j.biotechadv.2019.02.009 }}</ref> Another form of scaffold is decellularized tissue. This is a process where chemicals are used to extracts cells from tissues, leaving just the extracellular matrix. This has the benefit of a fully formed matrix specific to the desired tissue type. However, the decellurised scaffold may present immune problems with future introduced cells.{{cn|date=April 2025}}
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