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.

Smart ECM-Based Electrospun Biomaterials for Skeletal Muscle Regeneration

“…The mechanical properties, as well as the internal architecture of the scaffold, may play an important role in the regeneration of complex tissue such as skeletal muscle tissue, influencing cell proliferation, alignment, and myogenic differentiation. For this reason, electrospinning may provide a promising method for the fabrication of dECM-based scaffolds allowing for the modulation of architecture and mechanical properties [ 3 ].…”

“…Skeletal muscle is a complex system of oriented muscle fibers acting together to produce a contractile force and support body movement. In addition, the proper function of skeletal muscle encompasses breathing, metabolic control, thermoregulation, and energy storage [ 3 ]. Skeletal muscle has innate regenerative potential following injury or disease.…”

“…The potential strategies for designing a suitable biomaterial for skeletal muscle regeneration should take into account important physical, biochemical, and inflammatory cues that effectively affect cell adhesion and proliferation and thus guide muscle regeneration. Among the most important properties that biomaterials should possess for successful skeletal muscle TE include: porosity, aligned architecture, and bioavailability of bioactive molecules to promote the cell activity [ 3 ].…”

“…However, during a typical electrospinning process, fibers are densely deposited on a collector forming closed packed fibers that are associated with poor cell infiltration. To date, many interesting approaches are investigated to enhance porosity in electrospun scaffolds and to acquire pores of the suitable size in order to obtain greater cell infiltration [ 3 , 16 ].…”

“…The orientation of fibers is an important feature of an ideal and promising scaffold because this aspect greatly influences cell growth and related functions in cells such as nerve and smooth muscle cells [ 20 ]. In particular, the creation of polymeric aligned electrospun biomaterials that mimic skeletal muscle allows the efficient organization of muscle cells to form aligned myotubes during muscle regeneration [ 3 ].…”