Biomaterials for skeletal muscle tissue engineering

Abstract

Although skeletal muscle can naturally regenerate in response to minor injuries, more severe damage and myopathies can cause irreversible loss of muscle mass and function. Cell therapies, while promising, have not yet demonstrated consistent benefit, likely due to poor survival of delivered cells. Biomaterials can improve muscle regeneration by presenting chemical and physical cues to muscle cells that mimic the natural cascade of regeneration. This brief review describes strategies for muscle repair utilizing biomaterials that can provide signals to either transplanted or host muscle cells. These strategies range from approaches that utilize biomaterials alone to those that combine biomaterials with exogenous growth factors, ex vivo cultured cells, and extensive culture time.

Figure 1

Two general approaches of skeletal muscle tissue engineering. (A) Muscle cells and other supporting cells are combined with biomaterials in vitro, followed by transplantation either after extended culture to promote muscle formation, or immediately. (B) Biomaterials, either alone or combined with cytokines, growth factors, or cells secreting paracrine signals, are delivered to the body to induce regeneration by host muscle cells.

Figure 2

Examples of muscle cells combined with biomaterials. (A) Engineered skeletal muscle consisting of myoblasts seeded into a fibrin gel, with microposts acting as artifical tendons that aid in forming aligned myofibers. These engineered muscles may also include endothelial cells that form aligned vascular networks, and/or exogenous agrin and laminin to promote acetylcholine receptor clustering. (B) Macroporous alginate scaffold (left) immediately delivering myoblasts to an adjacent muscle injury site (right). This scaffold is modified with RGD peptides to promote myoblast adhesion to the material and also releases factors to promote myoblast migration and proliferation. Red, dotted arrows indicate direction of cell migration.

Figure 3

Different approaches to in situ skeletal muscle tissue engineering. (A) Controlled growth factor release from drug delivery biomaterial (left) to adjacent injured muscle (right) can promote muscle stem cell recruitment, as well as host innervation and angiogenesis. (B) Materials that can be remodeled by cells (left) can naturally drive in-growth of muscle cells in the absence of growth factors from adjacent muscle (right). (C) Immunomodulatory biomaterials (left) placed adjacent to muscle (right) can (1) recruit host anti-inflammatory M2 macrophages and Th2 T-cells. Following recruitment, (2) these cells can secrete paracrine factors to recruit host muscle cells to the material and/or drive endogenous muscle regeneration. Red, dotted arrows indicate direction of cell migration.