The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies

Abstract

Despite the robust regenerative capacity of skeletal muscle, there are a variety of congenital and acquired conditions in which the volume of skeletal muscle loss results in major permanent functional and cosmetic deficits. These latter injuries are referred to as volumetric muscle loss (VML) injuries or VML-like conditions, and they are characterized by the simultaneous absence of multiple tissue components (i.e., nerves, vessels, muscles, satellite cells, and matrix). There are currently no effective treatment options. Regenerative medicine/tissue engineering technologies hold great potential for repair of these otherwise irrecoverable VML injuries. In this regard, three-dimensional scaffolds have been used to deliver sustained amounts of growth factors into a variety of injury models, to modulate host cell recruitment and extracellular matrix remodeling. However, this is a nascent field of research, and more complete functional improvements require more precise control of the spatiotemporal distribution of critical growth factors over a physiologically relevant range. This is especially true for VML injuries where incorporation of a cellular component into the scaffolds might provide not only a source of new tissue formation but also additional signals for host cell migration, recruitment, and survival. To this end, we review the major features of muscle repair and regeneration for largely recoverable injuries, and then discuss recent cell- and/or growth factor-based approaches to repair the more profound and irreversible VML and VML-like injuries. The underlying supposition is that more rationale incorporation of exogenous growth factors and/or cellular components will be required to optimize the regenerative capacity of implantable therapeutics for VML repair.

Skeletal Muscle Tissue Engineering: Biomaterials-Based Strategies for the Treatment of Volumetric Muscle Loss

“…HGF fibrin microthreads resulted in a significantly higher recovered force production than injuries that received no treatment or treatment with a fibrin hydrogel alone. This work has been recently acknowledged as the only study of growth factor-based repair that evaluated functional recovery in an appropriate VML injury model [191]. Histological analysis showed myofibers adjacent to implanted EDC crosslinked microthreads, indicating that the aligned microthread architecture likely guides myofiber ingrowth and alignment [187].…”

FAP Beige Adipogenesis in Volumetric Muscle Loss

“…Current treatments for VML focus on ful lling the wound with acellular biomaterial with or without combination with a cellular component that promotes muscle regeneration [24]. Cells currently used for VML treatments are mainly myoblasts or other myogenic stem/progenitor cells [25,26]. In this study, we demonstrated that a nonmyogenic progenitor-FAP, when induced to BAT differentiation, can be used in treating VML.…”

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology

“…Intrinsic potential for functional rearrangement and healing is low in human muscle tissue, further diminishing with the advancement of biological age (Grasman et al, 2015;Passipieri and Christ, 2016). Without effective therapeutic management, severe and extensive tissue structural bias (e.g., volumetric muscle loss) is often predictive of poor clinical outcome, as spontaneous optimal healing is hindered or negated, which results in diminished contractility associated with fibrotic tissue formation (Montarras et al, 2005;Ciciliot and Schiaffino, 2010;Grogan et al, 2011;Sicari et al, 2014;Duffy et al, 2016).…”