From Grafts to Human Bioengineered Vascularized Skin Substitutes

Abstract

The skin plays an important role in the maintenance of the human’s body physiological homeostasis. It acts as a coverage that protects against infective microorganism or biomechanical impacts. Skin is also implied in thermal regulation and fluid balance. However, skin can suffer several damages that impede normal wound-healing responses and lead to chronic wounds. Since the use of autografts, allografts, and xenografts present source limitations and intense rejection associated problems, bioengineered artificial skin substitutes (BASS) have emerged as a promising solution to address these problems. Despite this, currently available skin substitutes have many drawbacks, and an ideal skin substitute has not been developed yet. The advances that have been produced on tissue engineering techniques have enabled improving and developing new arising skin substitutes. The aim of this review is to outline these advances, including commercially available skin substitutes, to finally focus on future tissue engineering perspectives leading to the creation of autologous prevascularized skin equivalents with a hypodermal-like layer to achieve an exemplary skin substitute that fulfills all the biological characteristics of native skin and contributes to wound healing.

Cytotoxicity and Epidermal Barrier Function Evaluation of Common Antiseptics for Clinical Use in an Artificial Autologous Skin Model

“…Currently, the gold standard treatment for these injuries is to use autologous skin grafts to prevent pathogen entry and maintain skin homeostasis. Nevertheless, due to the limit of available native skin, autologous skin grafts can become challenging when these injuries cover a large body surface area [ 4 , 5 ]. That is the reason why skin substitutes were designed to be used in addition to or as a replacement for autologous skin grafts [ 6 ].…”

“…That is the reason why skin substitutes were designed to be used in addition to or as a replacement for autologous skin grafts [ 6 ]. The most important functions of these substitutes are the prevention of wound infection, reducing pain, promoting wound healing, and the replacement of normal skin to restore its function [ 3 , 5 , 7 ].…”

Translational stem cell therapy: vascularized skin grafts in skin repair and regeneration

“…The table below summarizes some of the current engineered skin substitutes available clinically (Table 1 ). Current commercially available skin substitutes are not impeccable and the choice of skin substitutes may be curtailed by factors such as immune rejection, integration failure, high cost, limited cell sources and material incompatibility that impairs successful long-term engraftment [ 4 , 5 ]. For instance, Biobrane ® allows for a single-stage procedure to cover partial thickness wounds, but it is highly susceptible to contaminated wounds [ 6 ].…”

“…Several papers have explored the possible inclusion of a hypodermal layer within the skin construct that may contribute to graft viability [ 10 , 11 ]. Since the hypodermis primarily consists of endothelial cells (ECs) and adipocytes, the presence of such a layer in the graft provides thermoregulation and structural support against mechanical insults, as well as nutrients and signaling cues for vessel formation [ 5 ]. However, further studies are required to ascertain the clinical efficacy of a hypodermis-inclusive 3-layered skin graft [ 5 ].…”

“…Since the hypodermis primarily consists of endothelial cells (ECs) and adipocytes, the presence of such a layer in the graft provides thermoregulation and structural support against mechanical insults, as well as nutrients and signaling cues for vessel formation [ 5 ]. However, further studies are required to ascertain the clinical efficacy of a hypodermis-inclusive 3-layered skin graft [ 5 ]. Commercially available skin substitutes that promote angiogenesis do not attain the magnitudes required for good engraftment.…”