Advances in biomaterials for skeletal muscle engineering and obstacles still to overcome

Abstract

Repair of injured skeletal muscle is a sophisticated process that uses immune, muscle, perivascular, and neural cells. In acute injury, the robust endogenous repair process can facilitate complete regeneration with little to no functional deficit. However, in severe injury, the damage is beyond the capacity for self-repair, often resulting in structural and functional deficits. Aside from the insufficiencies in muscle function, the aesthetic deficits can impact quality of life. Current clinical treatments are significantly limited in their capacity to structurally and functionally repair the damaged skeletal muscle. Therefore, alternative approaches are needed. Biomaterial therapies for skeletal muscle engineering have leveraged natural materials with sophisticated scaffold fabrication techniques to guide cell infiltration, alignment, and differentiation. Advances in biomaterials paired with a standardized and rigorous assessment of resulting tissue formation have greatly advanced the field of skeletal muscle engineering in the last several years. Herein, we discuss the current trends in biomaterials-based therapies for skeletal muscle regeneration and present the obstacles still to be overcome before clinical translation is possible. With millions of people affected by muscle trauma each year, the development of a therapy that can repair the structural and functional deficits after severe muscle injury is pivotal.

Keywords: Scaffolds; Skeletal muscle regeneration; Tissue engineering; Volumetric muscle loss.

Graphical abstract

Fig. 1

Key properties for skeletal muscle regenerative therapies. Scaffolds for skeletal muscle engineering should incorporate one or more key properties to successfully recruit, align, and promote differentiation of myogenic cells. Porosity is essential for proper nutrient and waste transport. Aligned topographical cues are important to promote myotube alignment. Bioactive molecules aid in cell recruitment, proliferation, and differentiation for muscle regeneration. In addition, injectable systems are minimally invasive and shorten recovery time after surgical intervention.

Fig. 2

Tissue engineering approaches to regenerate skeletal muscle. In vitro engineering utilizes a preconditioned cell-laden construct to increase cell survival and promote greater graft integration and reinnervation. In vivo engineering leverages cells with other scaffold cues to promote host cell infiltration and increase the initiation of tissue regeneration. In situ engineering uses an acellular construct and relies on the topographical, biochemical, and physicochemical cues from the biomaterials to promote cell infiltration and tissue regeneration.