Immunomodulation and Biomaterials: Key Players to Repair Volumetric Muscle Loss

Abstract

Volumetric muscle loss (VML) is defined as a condition in which a large volume of skeletal muscle is lost due to physical insult. VML often results in a heightened immune response, resulting in significant long-term functional impairment. Estimates indicate that ~250,000 fractures occur in the US alone that involve VML. Currently, there is no active treatment to fully recover or repair muscle loss in VML patients. The health economics burden due to VML is rapidly increasing around the world. Immunologists, developmental biologists, and muscle pathophysiologists are exploring both immune responses and biomaterials to meet this challenging situation. The inflammatory response in muscle injury involves a non-specific inflammatory response at the injured site that is coordination between the immune system, especially macrophages and muscle. The potential role of biomaterials in the regenerative process of skeletal muscle injury is currently an important topic. To this end, cell therapy holds great promise for the regeneration of damaged muscle following VML. However, the delivery of cells into the injured muscle site poses a major challenge as it might cause an adverse immune response or inflammation. To overcome this obstacle, in recent years various biomaterials with diverse physical and chemical nature have been developed and verified for the treatment of various muscle injuries. These biomaterials, with desired tunable physicochemical properties, can be used in combination with stem cells and growth factors to repair VML. In the current review, we focus on how various immune cells, in conjunction with biomaterials, can be used to promote muscle regeneration and, most importantly, suppress VML pathology.

Keywords: VML; biomaterials; immune response; reconstructive therapies.

Figure 1

Immune response in VML: In mild or severe injury the host immune response is activated. The tissue-resident stem cells are recruited at the site and their proliferation begins. M1 and M2 macrophages are activated which clear the damage and repair the tissue and fibrosis D.

Figure 2

Schematic illustration of current biomaterial approaches for the treatment of VML.

Figure 3

Tissue engineering for VML: Tissue engineering techniques help to repair damaged or completely lost muscle in small (lab animals) and large animals including sheep and pigs by the combination of cells, growth factors, and biomaterial scaffolds. The engineered muscle is then transplanted in VML patients.

Figure 4

Cell transplantation in VML: As a result of the injury satellite cells are differentiated to generate muscle fibers in VML.