Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries

Abstract

Skeletal muscle injuries typically result from traumatic incidents such as combat injuries where soft-tissue extremity injuries are present in one of four cases. Further, about 4.5 million reconstructive surgical procedures are performed annually as a result of car accidents, cancer ablation, or cosmetic procedures. These combat- and trauma-induced skeletal muscle injuries are characterized by volumetric muscle loss (VML), which significantly reduces the functionality of the injured muscle. While skeletal muscle has an innate repair mechanism, it is unable to compensate for VML injuries because large amounts of tissue including connective tissue and basement membrane are removed or destroyed. This results in in a significant need to develop off-the-shelf biomimetic scaffolds to direct skeletal muscle regeneration. Here, the structure and organization of native skeletal muscle tissue is described in order to reveal clear design parameters that are necessary for scaffolds to mimic in order to successfully regenerate muscular tissue. We review the literature with respect to the materials and methodologies used to develop scaffolds for skeletal muscle tissue regeneration as well as the limitations of these materials. We further discuss the variety of cell sources and different injury models to provide some context for the multiple approaches used to evaluate these scaffold materials. Recent findings are highlighted to address the state of the field and directions are outlined for future strategies, both in scaffold design and in the use of different injury models to evaluate these materials, for regenerating functional skeletal muscle.

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Contraction of these muscles requires substantial energy, and the SM plays a structural (support soft tissues, posture) and functional (temperature regulation, skeletal movement) role in the body. SM hypertrophy is essential to growth/development and lifelong fitness; and these tissues regularly undergo regeneration (Grasman et al, 2015;Wolf et al, 2015). However, recovery from medical problems dictated by atrophy, nerve dysfunction or significant volumetric muscle loss (VML) is limited and typically results in irreversible scar formation (Grasman et al, 2015;Wolf et al, 2015).…”

“…The SMs are organized as bundled (fascicles), layered muscle fibers (myofibers) integrated with connective tissues, nerves, and blood vessels (Grasman et al, 2015). Contraction of these muscles requires substantial energy, and the SM plays a structural (support soft tissues, posture) and functional (temperature regulation, skeletal movement) role in the body.…”

“…SM hypertrophy is essential to growth/development and lifelong fitness; and these tissues regularly undergo regeneration (Grasman et al, 2015;Wolf et al, 2015). However, recovery from medical problems dictated by atrophy, nerve dysfunction or significant volumetric muscle loss (VML) is limited and typically results in irreversible scar formation (Grasman et al, 2015;Wolf et al, 2015). The application of nanomaterials in tissue engineering is expected to fulfill many niches in SM tissue regeneration and restoration.…”

“…Nonetheless, these materials are often toxic to cells in vitro and require modifications (coatings, surface proteins) to promote biocompatibility (Grasman et al, 2015;Wolf et al, 2015). Common examples include poly(lactic acid) (PLA), PEG, and poly(ϵ-caprolactone) (PCL).…”

“…Neurological applications -CNTF-producing cells encapsulated in polymers (Orive et al, 2009) (macular degeneration, Huntington disease) -NeuraGen and NeuroMatrix (Seil and Webster, 2010;Daly et al, 2012) (collagen type I -peripheral nerve repair) -Neurolac (Daly et al, 2012) (PCLC -peripheral nerve repair) Skeletal muscle reconstitution -SIS and UBM ECM scaffolds (Grasman et al, 2015) (VML defect recovery, small clinical study)…”