Decellularized Scaffolds for Skin Repair and Regeneration

Abstract

The skin is the largest organ in the body, fulfilling a variety of functions and acting as a barrier for internal organs against external insults. As for extensive or irreversible damage, skin autografts are often considered the gold standard, however inherent limitations highlight the need for alternative strategies. Engineering of human-compatible tissues is an interdisciplinary and active field of research, leading to the production of scaffolds and skin substitutes to guide repair and regeneration. However, faithful reproduction of extracellular matrix (ECM) architecture and bioactive content capable of cell-instructive and cell-responsive properties remains challenging. ECM is a heterogeneous, connective network composed of collagens, glycoproteins, proteoglycans, and small molecules. It is highly coordinated to provide the physical scaffolding, mechanical stability, and biochemical cues necessary for tissue morphogenesis and homeostasis. Decellularization processes have made it possible to isolate the ECM in its native and three-dimensional form from a cell-populated tissue for use in skin regeneration. In this review, we present recent knowledge about these decellularized biomaterials with the potential to be used as dermal or skin substitutes in clinical applications. We detail tissue sources and clinical indications with success rates and report the most effective decellularization methods compatible with clinical use.

The Human Epidermal Basement Membrane: A Shaped and Cell Instructive Platform That Aging Slowly Alters

“…Preserving rete ridges or creating rete ridge-mimicking patterns is a subject of great concern in tissue engineering strategies to promote rapid and robust DEJ formation. Studies of rete ridges have been conducted after application of autologous epithelial cells as composite grafts with decellularized dermis in patients and in animal models [65][66][67][68]. The slow deposition of basement membrane proteins and the lack of rete ridges or dermal papillae result in poor epidermal-dermal adhesion and functional outcomes for patients treated with cultured epithelial autograft [69][70][71][72].…”

In Vitro Analysis of Histology, Mechanics, and Safety of Radiation-free Pre-hydrated Human Acellular Dermal Matrix

“…The most common decellularization method involves the use of detergents such as SDS, which is considered an excellent agent for cell removal. When SDS was applied to human skin, porcine small intestinal submucosa, or fibroblast sheets, the efficiency of decellularization increased with concentration, although the overall ECM density, including the glycosaminoglycan content, decreased and the collagen fiber network was damaged [ 21 ]. In previous studies, SDS was applied at an average concentration of 0.5% w/v (range 0.1%–1%) [ 21 ].…”

“…When SDS was applied to human skin, porcine small intestinal submucosa, or fibroblast sheets, the efficiency of decellularization increased with concentration, although the overall ECM density, including the glycosaminoglycan content, decreased and the collagen fiber network was damaged [ 21 ]. In previous studies, SDS was applied at an average concentration of 0.5% w/v (range 0.1%–1%) [ 21 ]. H-ADM-low was produced using SDS at 0.25%, which is half of the average concentration, and HE staining showed that the matrix was completely decellularized, i.e., there were no residual cell debris or other immunogenic components of the native skin.…”

The Role of Collagen-Based Biomaterials in Chronic Wound Healing and Sports Medicine Applications

“…The commercial landscape of dermal allografts is complex and varied due to the many different processing strategies employed to retain or omit layers of the dermis, basement membrane, and epidermis. Therefore, skin tissue can be processed for many applications such as burns, reconstructive surgery, chronic or acute wounds, or soft tissue repair [ 47 , 48 ]. This review has highlighted an application of dermal allografts for sports medicine in tendon repair.…”