Abstract
Muscle regeneration can be permanently impaired by traumatic injuries, despite the high regenerative capacity of skeletal muscle. Implantation of engineered biomimetic scaffolds to the site of muscle ablation may serve as an attractive off-the-shelf therapeutic approach. The objective of the study was to histologically assess the therapeutic benefit of a three-dimensional spatially patterned collagen scaffold, in conjunction with rehabilitative exercise, for treatment of volumetric muscle loss. To mimic the physiologic organization of skeletal muscle, which is generally composed of myofibers aligned in parallel, three-dimensional parallel-aligned nanofibrillar collagen scaffolds were fabricated. When implanted into the ablated murine tibialis anterior muscle, the aligned nanofibrillar scaffolds, in conjunction with voluntary caged wheel exercise, significantly improved the density of perfused microvessels, in comparison to treatments of the randomly oriented nanofibrillar scaffold, decellularized scaffold, or in the untreated control group. The abundance of neuromuscular junctions was 19-fold higher when treated with aligned nanofibrillar scaffolds in conjunction with exercise, in comparison to treatment of aligned scaffold without exercise. Although, the density of de novo myofibers was not significantly improved by aligned scaffolds, regardless of exercise activity, the cross-sectional area of regenerating myofibers was increased by > 60% when treated with either aligned and randomly oriented scaffolds, in comparison to treatment of decellularized scaffold or untreated controls. These findings demonstrate that voluntary exercise improved the regenerative effect of aligned scaffolds by augmenting neurovascularization, and have important implications in the design of engineered biomimetic scaffolds for treatment of traumatic muscle injury.
Highlights
Skeletal muscle generally has high regenerative capacity, muscle regeneration can be permanently impaired by traumatic injuries
Scanning electron microscopy (SEM) imaging confirmed the parallelaligned orientation of nanofibrils within each aligned nanofibrillar scaffold, with nanofibril diameters of 50 nm (Fig. 1b)
Treatment of aligned scaffolds in conjunction with exercise led to significantly more mature neuromuscular junctions, Voluntary exercise and implanted aligned scaffolds on de novo myogenesis and innervation compared to the absence of exercise (Fig. 4)
Summary
Skeletal muscle generally has high regenerative capacity, muscle regeneration can be permanently impaired by traumatic injuries. Volumetric muscle loss (VML) is characterized by the removal of a significant portion of skeletal muscle,[1] leading to irreversible loss of muscle function as well as cosmetic deformity. Approaches to treat VML by autologous muscle flap transplantation or tissue debridement has shown limited benefit and donor site morbidity.[2,3,4] It has become increasingly appreciated that recovery from VML requires revascularization[5] and innervation.[6] Being highly metabolic, skeletal muscle is closely approximated to capillaries as a source of nutrients and oxygen to maintain muscle function and viability. Innervation of the newly regenerated muscle is important for long-term functional integration and restoration of VML injury.[7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
