Kavya Yeruva 

Introduction: Burns are one of the most common types of trauma, resulting in damage to the epidermis, dermis, and occasionally underlying tissue. The resulting pro-inflammatory response is initiated by vasodilation of nearby blood vessels and diapedesis of various cells into the injured area.^1,2,3 Macrophages then release cytokines like IL-6 and IL-1 and growth factors like TGF-α, PDGF, and VEGF.²  These factors promote angiogenesis as well as proliferation and migration of keratinocytes and fibroblasts.² Subsequent collagen deposition, basement membrane formation, ECM protein cross-linking, and re-epithelialization allow for wound healing.⁴ After initial first aid to prevent infection and shock, some deeper burn wounds may require skin grafts to restore the epithelial barrier and accelerate the healing process.^3,4 Although autografts, allografts, and xenografts are valuable options, bioprinted skin grafts appear to be the most promising due to the limited risk of immune rejection and reduced host skin harvesting requirements.² Methods: Studies tested the efficacy of different skin graft types by either using human burn patients or creating full-thickness excisional skin wounds in animal models.^5,7 Bioprinted skin grafts were created using a 3D printer that deposited overlapping layers of “bioink,” a customizable solution of hydrogel molecules, growth factors, and skin cells.⁶ These engineered skin substitutes were compared to autografts, acellular hydrogel grafts, and untreated control groups by measuring wound re-epithelialization, closure, and contraction.^5,6,7 Immunohistochemical methods were also used to visualize graft integration and ECM remodeling.⁶ Results: The precise deposition of keratinocytes, fibroblasts, and growth factors onto burn wounds allowed for the generation of complex, stratified grafts that better integrated into the underlying tissue.⁵  Therefore, bioprinted skin grafts allowed for accelerated re-epithelialization and reduced contraction when compared to controls.⁵ New blood vessels that were not part of the original engineered tissue were generated after application of the bioprinted skin grafts, indicating that angiogenesis was promoted by ancillary growth factors like VEGF.⁷ Similarly, successful ECM remodeling in the bioprinted grafts was also demonstrated by collagen cross-linking and keratin staining.⁶ Conclusions: Bioprinting allows for the creation of a specialized scaffold with the precise molecular and cellular components needed to mimic and even accelerate natural burn wound healing. Engineered grafts also pose an advantage over comparable autografts since they reduce reliance on donor skin and consequently reduce mortality rates in burn patients.⁷ Although cost might currently limit its widespread use, bioprinting is a highly promising option for the treatment of burn wounds.⁵

1.  Shpichka A, Butnaru D, Bezrukov EA, et al. Skin tissue regeneration for burn injury. Stem Cell Res Ther. 2019;10(1):94.
2. Roshangar L, Soleimani Rad J, Kheirjou R, Reza Ranjkesh M, Ferdowsi Khosroshahi A. Skin burns: Review of molecular mechanisms and therapeutic approaches. Wounds. 2019;31(12):308-315.
3. Nielson CB, Duethman NC, Howard JM, Moncure M, Wood JG. Burns: Pathophysiology of systemic complications and current management. J Burn Care Res. 2017;38(1):e469-e481.
4. Thiruvoth F, Mohapatra D, Sivakumar D, Chittoria R, Nandhagopal V. Current concepts in the physiology of adult wound healing. Plast Aesthet Res. 2015;2(5):250.
5. Albanna M, Binder KW, Murphy SV, et al. In situ bioprinting of autologous skin cells accelerates wound healing of extensive excisional full-thickness wounds. Sci Rep. 2019;9(1):1856.
6. Jorgensen AM, Varkey M, Gorkun A, et al. Bioprinted skin recapitulates normal collagen remodeling in full-thickness wounds. Tissue Eng Part A. 2020;26(9-10):512-526.
7. Boyce ST, Simpson PS, Rieman MT, et al. Randomized, paired-site comparison of autologous engineered skin substitutes and split-thickness skin graft for closure of extensive, full-thickness burns. J Burn Care Res. 2017;38(2):61-70.