Decellularized Extracellular Matrix-Derived Hydrogels: a Powerful Class of Biomaterials for Skeletal Muscle Regenerative Engineering Applications

Purpose: The extracellular matrix (ECM) is a complicated milieu consisting of structural and functional molecules secreted by the resident cells that provides an optimal microenvironmental niche for enhanced cell adhesion, growth, differentiation, and tissue formation and maturation. For decades, ECM bio-scaffolds prepared from decellularized tissues have been used to promote skeletal muscle regeneration; however, it was recently discovered that these decellularized ECM (dECM) materials can be further processed into hydrogels, thus expanding the potential applications of dECM materials in skeletal muscle regenerative engineering (SMRE). This review article highlights the recent advances in dECM-derived hydrogels toward skeletal muscle regeneration and repair. Method: We screened articles in PubMed and bibliographic search using a combination of keywords. Relevant and high-cited articles were chosen for inclusion in this narrative review. Results: Here, we discuss the skeletal muscle ECM’s structure, function, and biochemical composition with emphasis on the role of the ECM during skeletal muscle embryogenesis, growth, development, and repair. Furthermore, we review various hydrogels used to promote skeletal muscle regeneration. We also review the current applications of dECM-derived hydrogels toward SMRE. Finally, we discuss the clinical translation potential of dECM-derived hydrogels for skeletal muscle regeneration and repair and their potential clinical considerations in the future. Conclusion: Although much progress has been made in the field of dECM-derived hydrogels toward SMRE, it is still in its nascent stage. We believe improving and standardizing the methods of decellularization, lowering the immunogenicity of dECMs, and carrying out in vivo investigations in large animal models would advance their future clinical applications. Lay Summary: Researchers have discovered an effective way to turn tissue materials into jelly-like substances known as extracellular matrix (ECM)-derived hydrogels. These ECM-derived hydrogels can help muscles heal better after serious injuries. They can be injected into gaps or used to guide muscle growth in the lab or body. This review article explains how these ECM-derived hydrogels are made and how they can be used to improve muscle healing. It also discusses their possible use in clinics and what needs to be considered before using them for medical treatments.