Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease

Abstract

Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice.

Making muscle: skeletal myogenesisin vivoandin vitro

“…A similar concern has been raised about the physiological relevance and the proper maturation of the cell types generated in vitro, which in most cases reach only a fetal state (Robertson et al, 2013;Satin et al, 2008). For skeletal muscle, this is evidenced by the neonatal properties of the in vitro myofibers, including smaller size, immature metabolism and a weak physiological response (Bursac et al, 2015). Parameters that control the maturation of PSC-derived myofibers remain largely unexplored and the use of integrated co-culture systems or biomaterials has been seldom investigated (Chal et al, 2016;Leung et al, 2013).…”

Regeneration competent satellite cell niches in rat engineered skeletal muscle

“…Ideal tissue engineered skeletal muscle should display all characteristic morphological (ie for example fusion of myotubes to form a true syncytium) and functional (ie for example tetanic contractions upon high frequency stimulation) properties of native skeletal muscle . It should moreover contain functional satellite cell niches capable of muscle regeneration if activated by injury as this would allow to study muscle regeneration in the dish …”

“…[24][25][26] It should moreover contain functional satellite cell niches capable of muscle regeneration if activated by injury as this would allow to study muscle regeneration in the dish. 27 Here, we demonstrate that satellite cells from engineered skeletal muscle (ESM) are capable of regenerating muscle in vitro and in vivo. Satellite cells respond to pharmacological interventions demonstrating the principal utility of ESM in screens for regeneration inducing drugs in vitro.…”

In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease

“…On the other hand, therapies utilizing mature functional engineered muscle tissues face a significantly larger number of challenges. Fundamental issues with efficient restoration of SC niche, tissue prevascularization without functional loss, rapid anastomosis with host vasculature, and functional innervation upon implantation need to be all addressed before considering potential for translation [109,278] …”