Bioengineered Skin Substitutes: Advances and Future Trends
Source abstract
Abstract
As the largest organ in the human body, the skin has the function of maintaining balance and protecting from external factors such as bacteria, chemicals, and temperature. If the wound does not heal in time after skin damage, it may cause infection or life-threatening complications. In particular, medical treatment of large skin defects caused by burns or trauma remains challenging. Therefore, human bioengineered skin substitutes represent an alternative approach to treat such injuries. Based on the chemical composition and scaffold material, skin substitutes can be classified into acellular or cellular grafts, as well as natural-based or synthetic skin substitutes. Further, they can be categorized as epidermal, dermal, and composite grafts, based on the skin component they contain. This review presents the common commercially available skin substitutes and their clinical use. Moreover, the choice of an appropriate hydrogel type to prepare cell-laden skin substitutes is discussed. Additionally, we present recent advances in the field of bioengineered human skin substitutes using three-dimensional (3D) bioprinting techniques. Finally, we discuss different skin substitute developments to meet different criteria for optimal wound healing.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Electrospun Nanofibers in Biomedical Applications · Wound Healing and Treatments · 3D Printing in Biomedical Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
Tissue Biology Research Unit, University Children’s Hospital Zurich, University of Zurich, 8952 Schlieren, Switzerland
Children’s Research Center, University Children’s Hospital Zurich, 8032 Zurich, Switzerland
References (100+)
Show source-provided references
1. A review of tissue-engineered skin bioconstructs available for skin reconstruction10.1098/rsif.2009.0403 ↗
2. Definitions and guidelines for assessment of wounds and evaluation of healing10.1046/j.1524-475X.1994.20305.x ↗
3. A multifunctional nanocomposite spray dressing of Kappa-carrageenan-polydopamine modified ZnO/L-glutamic acid for diabetic wounds10.1016/j.msec.2020.110837 ↗
4. Anatomy, histology and immunohistochemistry of normal human skin
5. Comparison of human skin or epidermis models with human and animal skin in in-vitro percutaneous absorption10.1016/S0378-5173(00)00665-7 ↗
6. Tavakoli, S., and Klar, A.S. (2020). Advanced Hydrogels as Wound Dressings. Biomolecules, 10.10.3390/biom10081169 ↗
7. Skin tissue regeneration10.1533/9780857092915.2.298 ↗
8. Burn wound healing and treatment: Review and advancements10.1186/s13054-015-0961-2 ↗
9. Wound Healing Dressings and Drug Delivery Systems: A Review10.1002/jps.21210 ↗
10. Gaur, M., Dobke, M.K., and Lunyak, V.V. (2017). Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging. Int. J. Mol. Sci., 18.10.3390/ijms18010208 ↗
11. Injury Is a Major Inducer of Epidermal Innate Immune Responses during Wound Healing10.1038/jid.2009.284 ↗
12. Characterization of vasculogenic potential of human adipose-derived endothelial cells in a three-dimensional vascularized skin substitute10.1007/s00383-015-3808-7 ↗
13. Characterization of M1 and M2 polarization of macrophages in vascularized human dermo-epidermal skin substitutes in vivo10.1007/s00383-017-4179-z ↗
14. Macrophages in skin injury and repair10.1016/j.imbio.2011.01.001 ↗
15. Biologic and synthetic skin substitutes: An overview10.4103/0970-0358.70712 ↗
16. Science, medicine, and the future: Healing chronic wounds10.1136/bmj.324.7330.160 ↗
17. Critical Review in Oral Biology & Medicine: Factors Affecting Wound Healing10.1177/0022034509359125 ↗
18. Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair10.1089/wound.2013.0517 ↗
19. Wound Healing Angiogenesis: Innovations and Challenges in Acute and Chronic Wound Healing10.1089/wound.2011.0308 ↗
20. Tissue-engineered dermo-epidermal skin grafts prevascularized with adipose-derived cells10.1016/j.biomaterials.2014.02.049 ↗
21. The Crucial Role of Vascularization and Lymphangiogenesis in Skin Reconstruction10.1159/000492413 ↗
22. Vascularization is the next challenge for skin tissue engineering as a solution for burn management10.1093/burnst/tkaa022 ↗
23. Analysis of blood and lymph vascularization patterns in tissue-engineered human dermo-epidermal skin analogs of different pigmentation10.1007/s00383-013-3451-0 ↗
24. An update and review of cell-based wound dressings and their integration into clinical practice10.21037/atm.2016.12.44 ↗
25. Comparison of in vivo immune responses following transplantation of vascularized and non-vascularized human dermo-epidermal skin substitutes10.1007/s00383-016-4031-x ↗
26. Tissue Engineering: Challenges and Selected Application
27. Determining elastic properties of skin by measuring surface waves from an impulse mechanical stimulus using phase-sensitive optical coherence tomography10.1098/rsif.2011.0583 ↗
28. Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects
29. Concise Review: Role of Mesenchymal Stem Cells in Wound Repair10.5966/sctm.2011-0018 ↗
30. 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 trial10.1111/iwj.12329 ↗
31. The role of fibroblasts in tissue engineering and regeneration10.1111/j.1365-2133.2007.07914.x ↗
32. Grafix®, a Cryopreserved Placental Membrane, for the Treatment of Chronic/Stalled Wounds10.1089/wound.2015.0647 ↗
33. A Retrospective Clinical Study of 188 Consecutive Patients to Examine the Effectiveness of a Biologically Active Cryopreserved Human Skin Allograft (TheraSkin®) on the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers10.1177/1938640010387417 ↗
34. The use of cultured epithelial autograft in the treatment of major burn wounds: Eleven years of clinical experience10.1016/j.burns.2006.02.025 ↗
35. Coverage of full skin thickness burns with allograft inoculated with autogenous epithelial cells10.1016/0305-4179(86)90164-6 ↗
36. Cost-Efficacy of Cultured Epidermal Autografts in Massive Pediatric Burns10.1097/00000658-200006000-00011 ↗
37. Seria cultivation of strains of human epidemal keratinocytes: The formation keratinizin colonies from single cell is10.1016/S0092-8674(75)80001-8 ↗
38. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes
39. Efficacy of cultured epithelial autografts in pediatric burns and reconstructive surgery10.1016/S0039-6060(97)90054-4 ↗
40. Cultured epithelial autograft (CEA) in burn treatment: Three decades later10.1016/j.burns.2006.11.002 ↗
41. Long-term regeneration of human epidermis on third degree burns transplanted with autologous cultured epithelium grown on a fibrin matrix1, 210.1097/00007890-200012150-00009 ↗
42. Use of cultured epidermal autografts and dermal allografts as skin replacement after burn injury10.1016/S0140-6736(86)91838-6 ↗
43. Tops and flops using cultured epithelial autografts in children
44. Current Concepts in Pediatric Burn Care: Management of Burn Wounds with Cultured Epidermal Autografts*10.1055/s-2008-1063443 ↗
45. Silk fibroin–keratin based 3D scaffolds as a dermal substitute for skin tissue engineering10.1039/C4IB00208C ↗
46. The Efficacy and Safety of Dermagraft in Improving the Healing of Chronic Diabetic Foot Ulcers: Results of a prospective randomized trial10.2337/diacare.26.6.1701 ↗
47. Dermagraft: Use in the Treatment of Chronic Wounds10.1089/wound.2011.0282 ↗
48. What Makes the Optimal Wound Healing Material? A Review of Current Science and Introduction of a Synthetic Nanofabricated Wound Care Scaffold
49. A Metabolically Active Human Dermal Replacement for the Treatment of Diabetic Foot Ulcers10.1111/j.1525-1594.1997.tb00476.x ↗
50. (2020, December 28). Dermagraft: Use in the Treatment of Chronic Wounds—Google Scholar. Available online: https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Dermagraft%3A+Use+in+the+Treatment+of+Chronic+Wounds&btnG=.
51. Dermagraft®, a bioengineered human dermal equivalent for the treatment of chronic nonhealing diabetic foot ulcer10.1586/17434440.1.1.21 ↗
52. Treatment of venous leg ulcers with Dermagraft®10.1016/j.ejvs.2004.03.001 ↗
53. Use of dermagraft, a cultured human dermis, to treat diabetic foot ulcers10.2337/diacare.19.4.350 ↗
54. Scaffolds for epidermal tissue engineering10.1016/B978-0-08-102561-1.00007-5 ↗
55. Bilayered Bioengineered Skin Substitute (Apligraf®): A Review of Its Use in the Treatment of Venous Leg Ulcers and Diabetic Foot Ulcers10.2165/00063030-200216060-00005 ↗
56. Acute Excisional Wounds Treated with a Tissue-Engineered Skin (Apligraf)10.1046/j.1524-4725.1999.08186.x ↗
57. Skin Substitutes and Dermatology: A Review10.1007/s13671-013-0044-z ↗
58. Using a dermal skin substitute in the treatment of chronic wounds secondary to recessive dystrophic epidermolysis bullosa: A case series
59. Clinical trial of allogeneic cultured dermal substitute for the treatment of intractable skin ulcers in 3 patients with recessive dystrophic epidermolysis bullosa*10.1016/j.jaad.2003.08.013 ↗
60. Skingineering I: Engineering porcine dermo-epidermal skin analogues for autologous transplantation in a large animal model10.1007/s00383-010-2777-0 ↗
61. The use of a collagen sponge/living cell composite material to treat donor sites in burn patients10.1016/S0305-4179(03)00164-5 ↗
62. Osmotic expanders in children: No filling—No control—No problem?10.1055/s-0030-1270460 ↗
63. Novel Treatment for Massive Lower Extremity Avulsion Injuries in Children: Slow, but Effective with Good Cosmesis10.1055/s-0030-1267234 ↗
64. Giant naevus, giant excision, eleg (i) ant closure? Reconstructive surgery with Integra Artificial Skin® to treat giant congenital melanocytic naevi in children10.1016/j.bjps.2009.01.050 ↗
65. Human Adipose Mesenchymal Cells Inhibit Melanocyte Differentiation and the Pigmentation of Human Skin via Increased Expression of TGF-β110.1016/j.jid.2017.06.027 ↗
66. Skin Tissue Engineering: Application of Adipose-Derived Stem Cells10.1155/2017/9747010 ↗
67. Biologic attachment, growth, and differentiation of cultured human epidermal keratinocytes on a graftable collagen and chondroitin-6-sulfate substrate
68. Skin Anatomy and Antigen Expression after Burn Wound Closure with Composite Grafts of Cultured Skin Cells and Biopolymers10.1097/00006534-199304000-00010 ↗
69. The expression pattern of keratin 24 in tissue-engineered dermo-epidermal human skin substitutes in an in vivo model10.1007/s00383-017-4198-9 ↗
70. Collagen hydrogels strengthened by biodegradable meshes are a basis for dermo-epidermal skin grafts intended to reconstitute human skin in a one-step surgical intervention
71. Modified Plastic Compression of Collagen Hydrogels Provides an Ideal Matrix for Clinically Applicable Skin Substitutes10.1089/ten.tec.2011.0561 ↗
72. Isolation and Culture of Human Dermal Fibroblasts10.1007/978-1-4939-9473-1_6 ↗
73. Differential expression of granulocyte, macrophage, and hypoxia markers during early and late wound healing stages following transplantation of tissue-engineered skin substitutes of human origin10.1007/s00383-014-3616-5 ↗
74. Induction of angiogenic and inflammation-associated dermal biomarkers following acute UVB exposure on bio-engineered pigmented dermo-epidermal skin substitutes in vivo10.1007/s00383-018-4384-4 ↗
75. A Cultured Autologous Dermo-epidermal Skin Substitute for Full-Thickness Skin Defects: A Phase I, Open, Prospective Clinical Trial in Children10.1097/PRS.0000000000005746 ↗
76. Vascularization strategies for skin tissue engineering10.1039/D0BM00266F ↗
77. Skin tissue engineering: Wound healing based on stem-cell-based therapeutic strategies
78. Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin-collagen hydrogel: A clinical study for diabetic wound healing10.1002/term.3003 ↗
79. Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue10.1016/j.biomaterials.2011.04.064 ↗
80. 25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine10.1002/adma.201303233 ↗
81. Cell-laden hydrogels for tissue engineering10.1166/jbt.2014.1206 ↗
82. Polyisocyanopeptide hydrogels: A novel thermo-responsive hydrogel supporting pre-vascularization and the development of organotypic structures10.1016/j.actbio.2018.01.042 ↗
83. Nanocomposite hydrogel based on carrageenan-coated starch/cellulose nanofibers as a hemorrhage control material10.1016/j.carbpol.2020.117013 ↗
84. Sprayable and injectable visible-light Kappa-carrageenan hydrogel for in-situ soft tissue engineering10.1016/j.ijbiomac.2019.07.126 ↗
85. Zhu, J., Marchant, R., and Hu, J. (2013). Biomimetic hydrogels as scaffolds for tissue-engineering applications. Biomimetic Biomaterials: Structure and Applications, Woodhead Publishing.10.1533/9780857098887.2.238 ↗
86. Design and applications of man-made biomimetic fibrillar hydrogels10.1038/s41578-018-0077-9 ↗
87. Bioengineered skin substitutes for the management of burns: A systematic review10.1016/j.burns.2007.03.020 ↗
88. Treatment of partial-thickness burns: A prospective, randomized trial using TranscyteTM10.1111/j.1445-1433.2004.03106.x ↗
89. Fabrication of conducting electrospun nanofibers scaffold for three-dimensional cells culture10.1016/j.ijbiomac.2012.06.014 ↗
90. An injectable mechanically robust hydrogel of Kappa-carrageenan-dopamine functionalized graphene oxide for promoting cell growth10.1016/j.carbpol.2019.03.030 ↗
91. Hydrogel scaffolds for tissue engineering: Progress and challenges
92. Microporous cell-laden hydrogels for engineered tissue constructs10.1002/bit.22667 ↗
93. The influence of micropore size on the mechanical properties of bulk hydroxyapatite and hydroxyapatite scaffolds10.1016/j.jmbbm.2009.01.009 ↗
94. Li, Q., and Mai, Y.-W. (2017). Biomaterials for Implants and Scaffolds. Biomaterials Science and Engineering, Springer.10.1007/978-3-662-53574-5 ↗
95. Application of porous ceramics for the attachment of load bearing internal orthopedic applications10.1002/jbm.820050613 ↗
96. Micromolding of shape-controlled, harvestable cell-laden hydrogels10.1016/j.biomaterials.2006.06.005 ↗
97. Degradable, Thermo-Sensitive Poly(N-isopropyl acrylamide)-Based Scaffolds with Controlled Porosity for Tissue Engineering Applications10.1021/bm100521x ↗
98. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering10.1016/j.biomaterials.2017.03.021 ↗
99. Advances in bioprinted cell-laden hydrogels for skin tissue engineering10.1007/s40898-017-0003-8 ↗
100. 3D bioprinting of tissues and organs10.1038/nbt.2958 ↗