THE ROLE OF INNERVATION IN ENGINEERED MUSCLE

Skeletal muscle injuries span a wide spectrum, from minor strains to devastating traumatic events, and represent a significant clinical challenge worldwide. Millions of individuals experience severe muscle deficits each year, including volumetric muscle loss (VML) resulting from ballistic trauma, blast injury, surgical resection, and accidental damage. Such injuries are not restricted to any specific age group and often lead to long-term or permanent reductions in mobility, physical strength, and overall functional independence, placing a substantial burden on patients and healthcare system. Although skeletal muscle is an adaptable and highly regenerative tissue, its intrinsic repair mechanisms, driven primarily by resident satellite cells, are effective only for minor or moderate injuries. When tissue loss surpasses a critical threshold, the balance between regeneration and fibrosis is disrupted, leading to chronic deficits and incomplete functional recovery. Current clinical strategies for treating VML are limited. The standard approach, free functional muscle transfer, relies on autologous grafts that require multiple surgical sites, introduce risks of donor-site morbidity, and often fail to fully restore complex muscle architecture, vascularization, and innervation. No available therapy reliably reestablishes both the structural integrity and functional capacity of lost muscle, underscoring the urgent need for more advanced regenerative solutions. Recent efforts in tissue engineering aim to overcome these limitations by recapitulating key elements of the native regenerative microenvironment, including myogenic progenitors, supporting endothelial and neural networks, and extracellular matrix cues. Integrating principles from developmental muscle biology, neurosurgery, and biofabrication offers a promising path forward for constructing implantable muscle tissues capable of restoring contraction, perfusion, and neuromuscular connectivity. In this work, we apply these interdisciplinary strategies to develop a tissue-engineered platform designed to promote structural regeneration, vascular integration, and functional restoration in large muscle defects. This approach establishes a foundation for next-generation therapies targeting traumatic and degenerative muscle loss.

Author dc:creator

• Hilman, Melanie

Advisor dc:contributor.advisor

• Cullen, D., Kacy

• Engineering
• Neuroscience and Neurobiology

Language dc:language.iso

en

Repository record dc:identifier.uri

https://repository.upenn.edu/handle/20.500.14332/62385

OAI identifier oai:identifier

oai:repository.upenn.edu:20.500.14332/62385