Immunological challenges associated with artificial skin grafts: available solutions and stem cells in future design of synthetic skin

Abstract

The repair or replacement of damaged skins is still an important, challenging public health problem. Immune acceptance and long-term survival of skin grafts represent the major problem to overcome in grafting given that in most situations autografts cannot be used. The emergence of artificial skin substitutes provides alternative treatment with the capacity to reduce the dependency on the increasing demand of cadaver skin grafts. Over the years, considerable research efforts have focused on strategies for skin repair or permanent skin graft transplantations. Available skin substitutes include pre- or post-transplantation treatments of donor cells, stem cell-based therapies, and skin equivalents composed of bio-engineered acellular or cellular skin substitutes. However, skin substitutes are still prone to immunological rejection, and as such, there is currently no skin substitute available to overcome this phenomenon. This review focuses on the mechanisms of skin rejection and tolerance induction and outlines in detail current available strategies and alternatives that may allow achieving full-thickness skin replacement and repair.

Cultured Epidermal Autografts from Clinically Revertant Skin as a Potential Wound Treatment for Recessive Dystrophic Epidermolysis Bullosa

“…Developing fundamental regenerative medical treatments is challenging for severe inherited cutaneous disorders including EB, because allogeneic cells are prone to elimination by the host's immune systems (Dixit et al, 2017), and the use of autologous cells is limited unless the patient's own gene abnormalities are corrected. Several cell therapies for EB have been reported, such as allogeneic stem cell transplantation, allogeneic mesenchymal stromal cell injection, allogeneic fibroblast injection, and gene-corrected keratinocyte sheet transplantation (Bauer et al, 2017;Boull et al, 2016;Conget et al, 2010;El-Darouti et al, 2016;Geyer et al, 2015;Hirsch et al, 2017;Mavilio et al, 2006;Petrof et al, 2015;Siprashvili et al, 2016;Tolar and Wagner, 2013;Uitto et al, 2018;Wagner et al, 2010;Wong et al, 2008).…”

Establishment of a complex skin structure via layered co-culture of keratinocytes and fibroblasts derived from induced pluripotent stem cells

“…Due to the limited availability of autogenous donor tissue, the primary substitute is usually an allograft [ 4 ]. Unfortunately, an allograft is typically rejected by the host’s immune system after about 1 week and is therefore usually only used temporarily until an autograft can be applied [ 3 , 5 ].…”

A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

“…However, in the case of deep and/or large wounds or with extensive severe burns, the use of autografts is limited, and either allogeneic (from cadaver) or xenogeneic skin grafts are used for transplantation. Nevertheless, the use of allogeneic/xenogeneic tissue carries a high risk of graft rejection, limiting their clinical applications [46]. To overcome deficiency of donor skin graft supplies as well as skin allo/xenograft rejections, modern treatment includes skin tissue engineering aiming to produce bioengineered biomaterial-based artificial skin grafts [2,46].…”