We aim to generate clinical functional recovery after volumetric muscle loss by combining a neuromuscular pedicle embedded into novel scaffolds to provide regenerative cells and paracrine signaling.
The traumatic loss of a large volume of skeletal muscle andassociated functional debilitation is a significant clinical problem andcurrent treatments to restore the functional deficit of volumetric muscle loss(VML) remains the transfer of pedicled or innervated free muscle flaps into thedefect in conjunction with physical therapy. This approach leads to significant donor site morbidity by sacrificingexisting neuro-muscular flaps instead of promoting regeneration of lostskeletal muscle. Engineered tissueconstructs hold tremendous potential to achieve the muscle bulk and functionneeded for recovery. However, suchapproaches have been limited to the implantation of engineered muscle graftswith myocyte regeneration limited to the interface of the host skeletal musclein animal models. Innervation andvascularization of regenerated tissue remains a significant hurdle in creatingfunctional repairs of VML. Variousmuscle regeneration scaffolds have been evaluated without being able generatefull functional recovery. Using a smallanimal model, we aim to generate clinical functional recovery following a VMLby combining a small neuromuscular pedicle embedded into various musclescaffolds to provide regenerative paracrine signaling and host cells. Recovery will be evaluated through forcegeneration, vascular function, and histological and immunohistologic analysisof muscle structure, angiogenesis, and inflammation.
Our expected results are to demonstrate clinical functional recovery and regeneration following a volumetric muscle loss through a series of functional assays, including demonstrating improved in vivo integrated force generation and functional blood through the use of fluorescence angiography. We also expect that the addition of the pedicle flap into the scaffold will lead to improved tissue architecture as show by muscle fiber generation through histologic analysis. Results will be compared to control groups of no treatment and scaffolds alone.
Students and post-doctoral fellows will be used to generate the muscle scaffolds, perform the surgical defects and repairs,and the in vivo and ex vivo analysis, including tissue staining.