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Tissue engineering
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===Bioartificial organs=== {{main|Bioartificial organ}} An artificial organ is an engineered device that can be extra corporeal or implanted to support impaired or failing organ systems.<ref name=":5">{{cite journal | vauthors = Wang X | title = Bioartificial Organ Manufacturing Technologies | journal = Cell Transplantation | volume = 28 | issue = 1 | pages = 5โ17 | date = January 2019 | pmid = 30477315 | pmc = 6322143 | doi = 10.1177/0963689718809918 }}</ref> Bioartificial organs are typically created with the intent to restore critical biological functions like in the replacement of diseased hearts and lungs, or provide drastic quality of life improvements like in the use of engineered skin on burn victims.<ref name=":5" /> While some examples of bioartificial organs are still in the research stage of development due to the limitations involved with creating functional organs, others are currently being used in clinical settings experimentally and commercially.<ref>{{cite journal | vauthors = Sawa Y, Matsumiya G, Matsuda K, Tatsumi E, Abe T, Fukunaga K, Ichiba S, Kishida A, Kokubo K, Masuzawa T, Myoui A, Nishimura M, Nishimura T, Nishinaka T, Okamoto E, Tokunaga S, Tomo T, Tsukiya T, Yagi Y, Yamaoka T | display-authors = 6 | title = Journal of Artificial Organs 2017: the year in review : Journal of Artificial Organs Editorial Committee | journal = Journal of Artificial Organs | volume = 21 | issue = 1 | pages = 1โ7 | date = March 2018 | pmid = 29426998 | pmc = 7102331 | doi = 10.1007/s10047-018-1018-5 }}</ref> ==== Lung ==== [[Extracorporeal membrane oxygenation]] (ECMO) machines, otherwise known as heart and lung machines, are an adaptation of [[cardiopulmonary bypass]] techniques that provide heart and lung support.<ref name=":6">{{cite journal | vauthors = Chauhan S, Subin S | title = Extracorporeal membrane oxygenation, an anesthesiologist's perspective: physiology and principles. Part 1 | journal = Annals of Cardiac Anaesthesia | volume = 14 | issue = 3 | pages = 218โ29 | date = 2011-09-01 | pmid = 21860197 | doi = 10.4103/0971-9784.84030 | doi-access = free }}</ref> It is used primarily to support the lungs for a prolonged but still temporary timeframe (1โ30 days) and allow for recovery from reversible diseases.<ref name=":6" /> [[Robert Bartlett (surgeon)|Robert Bartlett]] is known as the father of ECMO and performed the first treatment of a newborn using an ECMO machine in 1975.<ref>{{Cite web|date=2017-06-20|title=How did ECMO get started?|url=https://uihc.org/health-topics/how-did-ecmo-get-started|access-date=2020-12-04|website=University of Iowa Hospitals & Clinics|language=en}}</ref> '''Skin''' Tissue-engineered skin is a type of bioartificial organ that is often used to treat burns, diabetic foot ulcers, or other large wounds that cannot heal well on their own. Artificial skin can be made from autografts, allografts, and xenografts. Autografted skin comes from a patient's own skin, which allows the dermis to have a faster healing rate, and the donor site can be re-harvested a few times. Allograft skin often comes from cadaver skin and is mostly used to treat burn victims. Lastly, xenografted skin comes from animals and provides a temporary healing structure for the skin. They assist in dermal regeneration, but cannot become part of the host skin.<ref name="auto1"/> Tissue-engineered skin is now available in commercial products. Integra, originally used to only treat burns, consists of a collagen matrix and chondroitin sulfate that can be used as a skin replacement. The chondroitin sulfate functions as a component of proteoglycans, which helps to form the extracellular matrix.<ref>{{Cite web|title=Chondroitin sulfate is a component of Integraยฎ Dermal Regeneration Template |url=https://fdocuments.us/document/chondroitin-sulfate-chondroitin-sulfate-is-a-component-of-integra-dermal-regeneration.html|access-date=2020-12-05|website=fdocuments.us|language=en}}</ref> Integra can be repopulated and revascularized while maintaining its dermal collagen architecture, making it a bioartificial organ<ref>{{Cite web|url=https://www.integralife.com/file/general/1525975889.pdf|title=Integra|accessdate=13 March 2023}}</ref> Dermagraft, another commercial-made tissue-engineered skin product, is made out of living fibroblasts. These fibroblasts proliferate and produce growth factors, collagen, and ECM proteins, that help build granulation tissue.<ref>{{Cite web|title=Dermagraft Human Fibroblast-derived Dermal Substitute|url=https://dermagraft.com/|access-date=2020-12-05|website=dermagraft.com}}</ref> ==== Heart ==== Since the number of patients awaiting a heart transplant is continuously increasing over time, and the number of patients on the waiting list surpasses the organ availability,<ref>{{cite journal | vauthors = Colvin M, Smith JM, Hadley N, Skeans MA, Uccellini K, Lehman R, Robinson AM, Israni AK, Snyder JJ, Kasiske BL | display-authors = 6 | title = OPTN/SRTR 2017 Annual Data Report: Heart | journal = American Journal of Transplantation | volume = 19 | issue = Suppl 2 | pages = 323โ403 | date = February 2019 | pmid = 30811894 | doi = 10.1111/ajt.15278 | s2cid = 73510324 | doi-access = free | hdl = 2027.42/172019 | hdl-access = free }}</ref> artificial organs used as replacement therapy for terminal heart failure would help alleviate this difficulty. Artificial hearts are usually used to bridge the heart transplantation or can be applied as replacement therapy for terminal heart malfunction.<ref>{{cite book | vauthors = Smith PA, Cohn WE, Frazier OH |chapter =Chapter 7 โ Total artificial hearts |doi = 10.1016/B978-0-12-810491-0.00007-2 | title =Mechanical Circulatory and Respiratory Support |publisher=Academic Press |pages=221โ44 |date=1 January 2018}}</ref> The total artificial heart (TAH), first introduced by Dr. Vladimir P. Demikhov in 1937,<ref>{{cite journal | vauthors = Khan S, Jehangir W | title = Evolution of Artificial Hearts: An Overview and History | journal = Cardiology Research | volume = 5 | issue = 5 | pages = 121โ25 | date = October 2014 | pmid = 28348709 | pmc = 5358116 | doi = 10.14740/cr354w }}</ref> emerged as an ideal alternative. Since then it has been developed and improved as a mechanical pump that provides long-term circulatory support and replaces diseased or damaged heart ventricles that cannot properly pump the blood, restoring thus the pulmonary and systemic flow.<ref>{{cite journal | vauthors = Melton N, Soleimani B, Dowling R | title = Current Role of the Total Artificial Heart in the Management of Advanced Heart Failure | journal = Current Cardiology Reports | volume = 21 | issue = 11 | pages = 142 | date = November 2019 | pmid = 31758343 | doi = 10.1007/s11886-019-1242-5 | s2cid = 208212152 }}</ref> Some of the current TAHs include AbioCor, an FDA-approved device that comprises two artificial ventricles and their valves, and does not require subcutaneous connections, and is indicated for patients with biventricular heart failure. In 2010 SynCardia released the portable freedom driver that allows patients to have a portable device without being confined to the hospital.<ref>{{cite journal | vauthors = Cook JA, Shah KB, Quader MA, Cooke RH, Kasirajan V, Rao KK, Smallfield MC, Tchoukina I, Tang DG | display-authors = 6 | title = The total artificial heart | journal = Journal of Thoracic Disease | volume = 7 | issue = 12 | pages = 2172โ80 | date = December 2015 | pmid = 26793338 | pmc = 4703693 | doi = 10.3978/j.issn.2072-1439.2015.10.70 }}</ref> ==== Kidney ==== While kidney transplants are possible, renal failure is more often treated using an artificial kidney.<ref name = "Tasnim_2010">{{cite journal | vauthors = Tasnim F, Deng R, Hu M, Liour S, Li Y, Ni M, Ying JY, Zink D | display-authors = 6 | title = Achievements and challenges in bioartificial kidney development | journal = Fibrogenesis & Tissue Repair | volume = 3 | issue = 14 | pages = 14 | date = August 2010 | pmid = 20698955 | doi = 10.1186/1755-1536-3-14 | pmc = 2925816 | doi-access = free }}</ref> The first artificial kidneys and the majority of those currently in use are extracorporeal, such as with hemodialysis, which filters blood directly, or peritoneal dialysis, which filters via a fluid in the abdomen.<ref name = "Tasnim_2010" /><ref name = "Humes_2014">{{cite journal | vauthors = Humes HD, Buffington D, Westover AJ, Roy S, Fissell WH | title = The bioartificial kidney: current status and future promise | journal = Pediatric Nephrology | volume = 29 | issue = 3 | pages = 343โ51 | date = March 2014 | pmid = 23619508 | doi = 10.1007/s00467-013-2467-y | s2cid = 19376597 }}</ref> In order to contribute to the biological functions of a kidney such as producing metabolic factors or hormones, some artificial kidneys incorporate renal cells.<ref name = "Tasnim_2010" /><ref name = "Humes_2014" /> There has been progress in the way of making these devices smaller and more transportable, or even [https://pharm.ucsf.edu/kidney implantable ]. One challenge still to be faced in these smaller devices is countering the limited volume and therefore limited filtering capabilities.<ref name = "Tasnim_2010" /> Bioscaffolds have also been introduced to provide a framework upon which normal kidney tissue can be regenerated. These scaffolds encompass natural scaffolds (e.g., decellularized kidneys,<ref>{{cite journal | vauthors = Su J, Satchell SC, Shah RN, Wertheim JA | title = Kidney decellularized extracellular matrix hydrogels: Rheological characterization and human glomerular endothelial cell response to encapsulation | journal = Journal of Biomedical Materials Research. Part A | volume = 106 | issue = 9 | pages = 2448โ2462 | date = September 2018 | pmid = 29664217 | pmc = 6376869 | doi = 10.1002/jbm.a.36439 }}</ref> collagen hydrogel,<ref>{{cite journal | vauthors = Lee SJ, Wang HJ, Kim TH, Choi JS, Kulkarni G, Jackson JD, Atala A, Yoo JJ | display-authors = 6 | title = In Situ Tissue Regeneration of Renal Tissue Induced by Collagen Hydrogel Injection | journal = Stem Cells Translational Medicine | volume = 7 | issue = 2 | pages = 241โ250 | date = February 2018 | pmid = 29380564 | pmc = 5788870 | doi = 10.1002/sctm.16-0361 }}</ref><ref>{{Cite journal | vauthors = Wu H, Zhang R, Hu B, He Y, Zhang Y, Cai L, Wang L, Wang G, Hou H, Qiu X |date=December 2021 |title=A porous hydrogel scaffold mimicking the extracellular matrix with swim bladder derived collagen for renal tissue regeneration |journal=Chinese Chemical Letters |language=en |volume=32 |issue=12 |pages=3940โ3947 |doi=10.1016/j.cclet.2021.04.043|s2cid=235570487 }}</ref> or silk fibroin<ref>{{cite journal | vauthors = Mou X, Shah J, Bhattacharya R, Kalejaiye TD, Sun B, Hsu PC, Musah S | title = A Biomimetic Electrospun Membrane Supports the Differentiation and Maturation of Kidney Epithelium from Human Stem Cells | journal = Bioengineering | volume = 9 | issue = 5 | pages = 188 | date = April 2022 | pmid = 35621466 | pmc = 9137565 | doi = 10.3390/bioengineering9050188 | doi-access = free }}</ref>), synthetic scaffolds (e.g., poly[lactic-co-glycolic acid]<ref>{{cite journal | vauthors = Lih E, Park KW, Chun SY, Kim H, Kwon TG, Joung YK, Han DK | title = Biomimetic Porous PLGA Scaffolds Incorporating Decellularized Extracellular Matrix for Kidney Tissue Regeneration | journal = ACS Applied Materials & Interfaces | volume = 8 | issue = 33 | pages = 21145โ21154 | date = August 2016 | pmid = 27456613 | doi = 10.1021/acsami.6b03771 }}</ref><ref>{{cite journal | vauthors = Burton TP, Callanan A | title = A Non-woven Path: Electrospun Poly(lactic acid) Scaffolds for Kidney Tissue Engineering | journal = Tissue Engineering and Regenerative Medicine | volume = 15 | issue = 3 | pages = 301โ310 | date = June 2018 | pmid = 30603555 | pmc = 6171675 | doi = 10.1007/s13770-017-0107-5 }}</ref> or other polymers), or a combination of two or more natural and synthetic scaffolds. These scaffolds can be implanted into the body either without cell treatment or after a period of stem cell seeding and incubation. In vitro and In vivo studies are being conducted to compare and optimize the type of scaffold and to assess whether cell seeding prior to implantation adds to the viability, regeneration and effective function of the kidneys. A recent systematic review and meta-analysis compared the results of published animal studies and identified that improved outcomes are reported with the use of hybrid (mixed) scaffolds and cell seeding;<ref>{{cite journal | vauthors = Mirmoghtadaei M, Khaboushan AS, Mohammadi B, Sadr M, Farmand H, Hassannejad Z, Kajbafzadeh AM | title = Kidney tissue engineering in preclinical models of renal failure: a systematic review and meta-analysis | journal = Regenerative Medicine | volume = 17 | issue = 12 | pages = 941โ955 | date = December 2022 | pmid = 36154467 | doi = 10.2217/rme-2022-0084 | s2cid = 252543376 }}</ref> however, the meta-analysis of these results were not in agreement with the evaluation of descriptive results from the review. Therefore, further studies involving larger animals and novel scaffolds, and more transparent reproduction of previous studies are advisable.
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