Hydrogels for Skeletal Muscle Regeneration

Skeletal muscle is made up of hundreds of multinucleated, aligned fibers that work together during contraction. While smaller injuries are typically able to be repaired by the body, large volumetric muscle loss (VML) typically results in loss of function. Tissue engineering (TE) applications that use cells seeded onto hydrogels are one potential option for regenerating the lost tissue. Hydrogels are described as soft crosslinked polymeric networks with high water content that simulates the body's natural aqueous environment. They can be formulated from many different starting materials into biocompatible, biodegradable systems. Fabrication methods such as electrospinning, freeze-drying, molding, and 3D printing can be used with the hydrogel solution to form 3D structures. In this review, natural, semi-synthetic, synthetic, and composite hydrogels for skeletal muscle regeneration are discussed. It was ascertained that the majority of the current research focused on natural polymeric hydrogels including collagen, gelatin, agarose, alginate, fibrin, chitosan, keratin, and combinations of the aforementioned. This category was followed by a discussion of composite hydrogels, defined in this review as at least one synthetic and one natural polymer combined to form a hydrogel, and these are the next most favored materials. Synthetic polymer hydrogels came in third with semi-synthetic polymers, chemically modified natural polymers, being the least common. While many of the hydrogels show promise for skeletal muscle regeneration, continued investigation is needed in order to regenerate a functional muscle tissue replacement. Lay Summary Skeletal muscle tissue engineering focuses on regenerating large amounts of skeletal muscle tissue lost due to tumor removal, traumatic injuries, and/or disease. Neither natural repair processes by the body nor current medical interventions are able to completely restore function after volumetric muscle loss. Thus, scientists are investigating alternative approaches to regenerate the lost muscle, restore function, and increase patient quality of life. This review paper summarizes the research from 2013 to early 2018 using hydrogels, a soft material with a high water content, as a tool to regenerate muscle. The review is categorized into hydrogels made from natural materials, semi-synthetic materials, synthetic materials, and composite materials (at least one natural and one synthetic material combined).