Abstract

Large-scale muscle injury in humans initiates a complex regeneration process, as not only the muscular, but also the vascular and neuro-muscular compartments have to be repaired. Conventional therapeutic strategies often fall short of reaching the desired functional outcome, due to the inherent complexity of natural skeletal muscle. Tissue engineering offers a promising alternative treatment strategy, aiming to achieve an engineered tissue close to natural tissue composition and function, able to induce long-term, functional regeneration after in vivo implantation. This review aims to summarize the latest approaches of tissue engineering skeletal muscle, with specific attention toward fabrication, neuro-angiogenesis, multicellularity and the biochemical cues that adjuvate the regeneration process.

Highlights

  • Volumetric muscle loss (VML) occurs after an abrupt loss of skeletal muscle, often due to surgical resection, trauma or burns

  • We will elucidate the three major aspects of tissue engineering skeletal muscle grafts we identified as crucial strategies for fabricating grafts designed for surgical implantation (Figure 1)

  • Poly(ethylene glycol) diacrylate (PEGDA) conjugated with porcine cholecystic derived ECM, formed biocompatible hydrogel suitable for growth and maturation of C2C12

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Summary

Introduction

Volumetric muscle loss (VML) occurs after an abrupt loss of skeletal muscle, often due to surgical resection, trauma or burns. There is currently no exact definition for VML, yet when a critical level of muscle loss is surpassed, a functional recovery is no longer possible. Scar tissue is deposited mostly by fibroblasts and an array of pathways lead the attempted regeneration [1]. The quantitative threshold of how much muscle loss can spontaneously be recovered post-injury is open to debate and seems location (muscle) and species dependent, with the limit having been reported, for example, at 15% in mice [2] and 30% in rats [3], while leading to a dysregulation of the neuromotor and fibrotic response. Lengthy treatment follow-ups and recurring operations lead to a high rate of patient dissatisfaction accompanied by the traumatic and stressful burden of an impaired everyday life

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