Abstract
Millions of Americans suffer from skeletal muscle injuries annually that can result in volumetric muscle loss (VML), where extensive musculoskeletal damage and tissue loss result in permanent functional deficits. In the case of small-scale injury skeletal muscle is capable of endogenous regeneration through activation of resident satellite cells (SCs). However, this is greatly reduced in VML injuries, which remove native biophysical and biochemical signaling cues and hinder the damaged tissue’s ability to direct regeneration. The current clinical treatment for VML is autologous tissue transfer, but graft failure and scar tissue formation leave patients with limited functional recovery. Tissue engineering of instructive biomaterial scaffolds offers a promising approach for treating VML injuries. Herein, we review the strategic engineering of biophysical and biochemical cues in current scaffold designs that aid in restoring function to these preclinical VML injuries. We also discuss the successes and limitations of the three main biomaterial-based strategies to treat VML injuries: acellular scaffolds, cell-delivery scaffolds, and in vitro tissue engineered constructs. Finally, we examine several innovative approaches to enhancing the design of the next generation of engineered scaffolds to improve the functional regeneration of skeletal muscle following VML injuries.
Highlights
A total of 65.8 million Americans suffer from musculoskeletal injuries annually, with treatment costs exceeding 176 billion dollars [1,2,3,4,5]
It consists of glycosaminoglycans (GAGs) and proteoglycans, such as heparan sulfate, which act as reservoirs for growth factors essential for myogenesis, including hepatocyte growth factor (HGF) and fibroblast growth factor 2 (FGF2) [32,33,34]
This study suggests that fibrin microthreads in combination with muscle-derived precursor cells (MDPCs) are a promising scaffold for treating volumetric muscle loss (VML) defects
Summary
A total of 65.8 million Americans suffer from musculoskeletal injuries annually, with treatment costs exceeding 176 billion dollars [1,2,3,4,5]. VML injuries result in significant long-term disability that does not improve over time [13,14] These extremity wounds represent the largest projected disability costs of combat injuries [10,15]. In the case of small-scale injuries or strains, muscle is capable of endogenous regeneration and complete functional restoration This ability is abated in VML, where the native biophysical and biochemical signaling cues are no longer present to facilitate regeneration. The current standard of care for VML is autologous tissue transfer, where a muscle flap is excised from an undamaged muscle and grafted into the injury site [19,20,21,22] This procedure is commonly referred to as a free functional muscle transfer (FFMT). A clinical need exists for the development of an alternative treatment that will restore function in VML injuries
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