Abstract

Effective clinical treatments for volumetric muscle loss resulting from traumatic injury or resection of a large amount of muscle mass are not available to date. Tissue engineering may represent an alternative treatment approach. Decellularization of tissues and whole organs is a recently introduced platform technology for creating scaffolding materials for tissue engineering and regenerative medicine. The muscle stem cell niche is composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells that form an intricate extracellular matrix (ECM) network in equilibrium with the surrounding cells and growth factors. A consistent body of evidence indicates that ECM proteins regulate stem cell differentiation and renewal and are highly relevant to tissue engineering applications. The ECM also provides a supportive medium for blood or lymphatic vessels and for nerves. Thus, the ECM is the nature's ideal biological scaffold material. ECM-based bioscaffolds can be recellularized to create potentially functional constructs as a regenerative medicine strategy for organ replacement or tissue repopulation. This article reviews current strategies for the repair of damaged muscle using bioscaffolds obtained from animal ECM by decellularization of small intestinal submucosa (SIS), urinary bladder mucosa (UB), and skeletal muscle, and proposes some innovative approaches for the application of such strategies in the clinical setting.

Highlights

  • Tissue engineering aims to mimic neo-organogenesis to produce ex-vivo living tissue (Carosio et al, 2013)

  • Decellularization of tissues and whole organs is a recently introduced platform technology for creating scaffolding materials composed of an extracellular matrix (ECM) for skeletal muscle tissue engineering

  • Owing to the scarcity of studies on skeletal musclederived ECM, the present review investigates the reconstruction of skeletal muscle tissue based on both skeletal muscle and nonskeletal muscle (SIS and urinary bladder mucosa (UB)) ECM decellularized tissue

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Summary

INTRODUCTION

Tissue engineering aims to mimic neo-organogenesis to produce ex-vivo living tissue (Carosio et al, 2013). The afore-mentioned studies demonstrate (i) that native ECM-derived scaffold from various tissues can be obtained by means of different protocols that may require several days (Gilbert et al, 2006), and (ii) that this scaffold supports growth and survival of myogenic cells both in vitro and in vivo, and that it represents a pro-myogenic environment. We believe that each of these studies unveils important information on the native-ECM derived scaffold used to reconstruct skeletal muscle tissue: on its ability to support cell viability and growth in vitro, to provide a pro-myogenic environment in vivo, to elicit an immune response polarized toward an M2 macrophage phenotype and to preserve its molecular and structural features, as well as on the time and mode of decellularization and possible storage conditions.

CHARACTERIZATION OF ECM BIOSCAFFOLDS
Dog small intestinal submucosa
Rat tibialis anterior muscle
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