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.

Highlights

  • Skin is the largest organ in vertebrates and fulfills a variety of functions

  • We focus on decellularized biomaterials with the potential to be used as dermal or skin substitutes for clinical applications

  • Great advances have been made in skin regenerative medicine with regard to the preparation and use of decellularized tissues, leading to a growing number of products used in clinics with great success

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Summary

Introduction

Skin is the largest organ in vertebrates and fulfills a variety of functions. Acting primarily as a barrier protecting the internal organs from external insults, it fulfills other functions such as controlling fluid homeostasis, sensory detection, vitamin D synthesis, immune surveillance, and self-healing. Sci. 2020, 10, 3435 layer, constituting the lower part of the dermis, has a denser and thicker ECM network with fewer nerve fibers and capillaries In this sublayer, collagen fibers are aggregated into thick bundles that are largely aligned parallel to the skin surface [6,7]. Despite technological progress and advances in polymer science, the vast majority of artificial scaffolds do not perfectly mimic ECM scaffolding and bioactive cell-instructive and cell-responsive properties These aspects are challenging for skin repair because regeneration of the different skin layers requires different cell types and matrix elements. The pronounced effect of decellularized ECM scaffolds in supporting tissue regeneration is based on two major characteristics: first, the maintenance of the 3D structure, providing support, tensile strength, and attachment sites for cell surface receptors; and second, the availability of bioactive components that modulate angiogenesis, cell migration, and cell proliferation and orientation in wound healing [25]

Tissue Sources for Preparation of ECM-Based Biomaterials for Skin Repair
Animal-Derived ADMs
Decellularized Mesothelium
Decellularized Intestine and Urinary Bladder
Decellularized Skin Flaps
Decellularization Methods
Enzymes
Chemicals
Organic Solvents
Detergents
Acids and Bases
Promising New Approaches
Sterilization and Storage of Decellularized Scaffolds
Findings
Conclusions
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