Abstract

Skin substitutes are a heterogeneous group of biologic, synthetic, or biosynthetic materials that can provide coverage of open skin wounds. The aim of skin substitutes is to replicate the properties of the normal skin. Biocompatibility, antimicrobial activity, appropriate hydrophilicity, and biodegradability are all desirable qualities in a skin substitute. The goal of tissue engineering research is to develop cell-based wound substitutes or wound covers that promote cell migration, differentiation, and vascularization to facilitate wound healing.

• 1.   Shevchenko, R.V.; James, S.E. A review of tissueengineered skin bioconstructs available for skin reconstruction. J. R. Soc. Interface 2009, 7, 229–258.[CrossRef] [PubMed]
• 2.   Rowan, M.P.; Cancio, L.C.; Elster, E.A.; Burmeister, D.M.; Rose, L.F.; Natesan, S.; Chan, R.K.; Christy, R.J.; Chung, K.K. Burn wound healing and treatment: Review and advancements. Crit. Care 2015, 19, 1–12. [CrossRef] [PubMed]
• 3.   Klar, A.S.; Michalak-Mi´cka, K.; Biedermann, T.; Simmen-Meuli, C.; Reichmann, E.; Meuli, M. Characterization of M1 and M2polarization of macrophages in vascularized human dermoepidermal skin substitutes in vivo. Pediatr. Surg. Int. 2017, 34, 129–135. [CrossRef]
• 4.   Pogorielov, M.; Hapchenko, A.; Pogorielov, O.O.M. Tissue Engineering: Challenges and Selected Application. Adv. Tissue Eng.Regen. Med. Open Access 2017, 3, 1–6.[CrossRef]
• 5.   Olena, P.; Prokopyuk, V.; Figueiredo, C.; Pogozhykh, D. Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects. Stem Cells Int. 2018, 2018, 1–14. [CrossRef]
• 6.   Maxson, S.; Lopez, E.A.; Yoo, D.; DanilkovitchMiagkova, A.; Leroux, M.A. Concise Review: Role of Mesenchymal Stem Cells in Wound Repair. STEM CELLS Transl. Med. 2012, 1, 142–149. [CrossRef]
• 7.   Lavery, L.A.; Fulmer, J.; Shebetka, K.A.; Regulski, M.; Vayser, D.; Fried, D.; Kashefsky, H.; Owings, T.M.; Nadarajah, J. The Grafix Diabetic Foot Ulcer Study Group The efficacy and safety of Grafix® for the treatment of chronic diabetic foot ulcers: Results of a multi-centre, controlled, randomised, blinded, clinical trial. Int. Wound J. 2014, 11, 554–560. [CrossRef] [PubMed]
• 8.   Wood, F.M.; Kolybaba, M.; Allen, P. The use of cultured epithelial autograft in the treatment of major burn wounds: Eleven years of clinical experience. Burns 2006, 32, 538–544. [CrossRef] [PubMed]
• 9.   Barret, P.J.;Wolf, S.E.; Desai, M.H.; Herndon, D.N. Cost-Efficacy of Cultured Epidermal Autografts in Massive Pediatric Burns. Ann. Surg. 2000, 231, 869–876. [CrossRef]
• 10.   Marston, W.A.; Hanft, J.; Norwood, P.; Pollak, R. The Efficacy and Safety of Dermagraft in Improving the Healing of Chronic Diabetic Foot Ulcers: Results of a prospective randomized trial. Diabetes Care 2003, 26, 1701–1705. [CrossRef]
• 11.   Hart, C.E.; Loewen-Rodriguez, A.; Lessem, J. Dermagraft: Use in the Treatment of Chronic Wounds. Adv. Wound Care 2012, 1, 138–141.[CrossRef]
• 12.   Kumar, S.; Kang, H.J.; Berthiaume, F. Scaffolds for epidermal tissue engineering. In Handbook of Tissue Engineering Scaffolds; Woodhead Publishing: Cambridge, UK, 2019; Volume 2, pp. 173–191.
• 13.   Curran, M.P.; Plosker, G.L. Bilayered Bioengineered Skin Substitute (Apligraf®): A Review of Its Use in the Treatment of Venous Leg Ulcers and Diabetic Foot Ulcers. BioDrugs2002, 16, 439–455. [CrossRef] [PubMed]
• 14.   Pourmoussa, A.; Gardner, D.J.; Johnson, M.B.; Wong, A.K. An update and review of cell-based wound dressings and their integration into clinical practice. Ann. Transl. Med. 2016, 4, 457. [CrossRef]
• 15.   Braziulis, E.; Biedermann, T.; Hartmann-Fritsch, F.; Schiestl, C.; Pontiggia, L.; Böttcher-Haberzeth, S.; Reichmann, E.; Meuli, M.Skingineering I: Engineering porcine dermo-epidermal skin analogues for autologous transplantation in a large animal model.Pediatr. Surg. Int. 2011, 27, 241–247. [CrossRef]
• 16.   Schiestl, C.; Neuhaus, K.; Biedermann, T.; BöttcherHaberzeth, S.; Reichmann, E.; Meuli, M. Novel Treatment for Massive Lower Extremity Avulsion Injuries in Children: Slow, but Effective with Good Cosmesis. Eur. J. Pediatr. Surg. 2010, 21, 106–110. [CrossRef]
• 17.   Schiestl, C.; Stiefel, D.; Meuli, M. Giant naevus, giant excision, eleg (i) ant closure? Reconstructive surgery with Integra ArtificialSkin® to treat giant congenital melanocytic naevi in children. J. Plast. Reconstr. Aesthet. Surg. 2010, 63, 610–615. [CrossRef]
• 18.   Zimoch, J.; Padial, J.S.; Klar, A.S.; Vallmajo-Martin, Q.; Meuli, M.; Biedermann, T.; Wilson, C.J.; Rowan, A.; Reichmann, E. Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures. ActaBiomater. 2018, 70, 129–139. [CrossRef]
• 19.   Tavakoli, S.; Kharaziha, M.; Nemati, S.; Kalateh, A. Nanocomposite hydrogel based on carrageenancoated starch/cellulose nanofibers as a hemorrhage control material. Carbohydr. Polym. 2021, 251, 117013. [CrossRef]
• 20.   Tavakoli, S.; Kharaziha, M.; Kermanpur, A.; Mokhtari, H. Sprayable and injectable visible-light Kappa-carrageenan hydrogel for in-situ soft tissue engineering. Int. J. Biol. Macromol. 2019, 138, 590–601. [CrossRef] [PubMed]
• 21.   Rana, D.; Kumar, T.S.; Ramalingam, M. Cell-laden hydrogels for tissue engineering. J. Biomater. Tissue Eng. 2014, 4, 507–535.[CrossRef]
• 22.   Q.; Mai, Y.-W. Biomaterials for Implants and Scaffolds. In Biomaterials Science and Engineering; Springer: Berlin, Germany, 2017; Volume 8, ISBN 978-3-662-53572-1.
• 23.   Klawitter, J.J.; Hulbert, S.F. Application of porous ceramics for the attachment of load bearing internal orthopedic applications. J.Biomed. Mater. Res. 1971, 5, 161–229. [CrossRef]
• 24.   Yeh, J.; Blumling, J.; Karp, J.M.; Gantz, J.; Chandawarkar, A.; Eng, G.; Iii, J.B.; Langer, R.; Khademhosseini, A. Micromolding of shapecontrolled, harvestable cell-laden hydrogels. Biomaterials 2006, 27, 5391–5398. [CrossRef] [PubMed]
• 25.   Eke, G.; Mangir, N.; Hasirci, N.; MacNeil, S.; Hasirci, V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials 2017, 129, 188–198. [CrossRef]
• 26.   Murphy, S.V.; Atalaa, A. 3D bioprinting of tissues and organs. Nat. Biotechnol. 2014, 32, 773–785. [CrossRef]
• 27.   Li, H.; Tan, C.; Li, L. Review of 3D printable hydrogels and constructs. Mater. Des. 2018, 159, 20–38. [CrossRef]
• 28.   Hng, G.; Li, F.; Zhao, X.; Ma, Y.; Li, Y.; Min, L.; Jin, G.; Lu, T.J.; Genin, G.M.; Xu, F. Functional and Biomimetic Materials for Engineering of the ThreeDimensional Cell Microenvironment. Chem. Rev. 2017, 117, 12764–12850. [CrossRef] [PubMed]
• 29.   Yanez, M.; Rincon, J.; Dones, A.; De Maria, C.; Gonzales, R.; Boland, T. In Vivo Assessment of Printed Microvasculature in a Bilayer Skin Graft to Treat Full-Thickness Wounds. Tissue Eng. Part A2015, 21, 224–233. [CrossRef]
• 30.   Albanna, M.; Binder, K.W.; Murphy, S.V.; Kim, J.; Qasem, S.A.; Zhao, W.; Tan, J.; El-Amin, I.B.; Dice, D.D.; Marco, J.; et al. In SituBioprinting of Autologous Skin Cells Accelerates Wound Healing of Extensive Excisional Full-Thickness Wounds. Sci. Rep. 2019,9, 1–15. [CrossRef] [PubMed]
• 31.   Hafezi, F.; Scoutaris, N.; Douroumis, D.; Boateng, J.S. 3D printed chitosan dressing crosslinked with genipin for potential healingof chronic wounds. Int.J. Pharm. 2019, 560, 406–415. [CrossRef]
• 32.   Admane, P.; Gupta, A.C.; Jois, P.; Roy, S.; Lakshmanan, C.C.; Kalsi, G.; Bandyopadhyay, B.; Ghosh, S. Direct 3D bioprintedfullthicknessskin constructs recapitulate regulatory signaling pathways and physiology of human skin. Bioprinting2019, 15, e00051.[CrossRef]

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Funding