There are no effective clinical treatments for volumetric muscle loss (VML) resulting from traumatic injury, tumor excision, or other degenerative diseases of skeletal muscle. The goal of this study was to develop and characterize a more clinically relevant tissue-engineered muscle repair (TE-MR) construct for functional restoration of a VML injury in the mouse lattissimus dorsi (LD) muscle. To this end, TE-MR constructs developed by seeding rat myoblasts on porcine bladder acellular matrix were preconditioned in a bioreactor for 1 week and implanted in nude mice at the site of a VML injury created by excising 50% of the native LD. Two months postinjury and implantation of TE-MR, maximal tetanic force was ∼72% of that observed in native LD muscle. In contrast, injured LD muscles that were not repaired, or were repaired with scaffold alone, produced only ∼50% of native LD muscle force after 2 months. Histological analyses of LD tissue retrieved 2 months after implantation demonstrated remodeling of the TE-MR construct as well as the presence of desmin-positive myofibers, blood vessels, and neurovascular bundles within the TE-MR construct. Overall, these encouraging initial observations document significant functional recovery within 2 months of implantation of TE-MR constructs and provide clear proof of concept for the applicability of this technology in a murine VML injury model.

Bone tissue engineering (BTE) is emerging as a possible solution for regeneration of bone in a number of applications. For effective utilization, BTE scaffolds often need modifications to impart biological cues that drive diverse cellular functions such as adhesion, migration, survival, proliferation, differentiation, and biomineralization. This review provides an outline of various approaches for building bioactive elements into synthetic scaffolds for BTE and classifies them broadly under two distinct schemes; namely, the top-down approach and the bottom-up approach. Synthetic and natural routes for top-down approaches to production of bioactive constructs for BTE, such as generation of scaffold-extracellular matrix (ECM) hybrid constructs or decellularized and demineralized scaffolds, are provided. Similarly, traditional scaffold-based bottom-up approaches, including growth factor immobilization or peptide-tethered scaffolds, are provided. Finally, a brief overview of emerging bottom-up approaches for generating biologically active constructs for BTE is given. A discussion of the key areas for further investigation, challenges, and opportunities is also presented.

Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR–MDC constructs as previously reported.