Investigating Neural Cell Behavior in Collagen Scaffolds for Skeletal Muscle Tissue Engineering

Volumetric muscle loss (VML) is a traumatic injury to skeletal muscle that supersedes the body’s natural wound healing capabilities. Current treatments for VML involve surgical operation using muscle from other parts of the body, which often results in poor functional recovery and donor site morbidity. Biomaterials research offers an alternative solution, aiming to guide native regeneration and improve functional recovery in VML injuries. Our research introduces a matrix for cell growth through aligned 3D collagen scaffolds. These scaffolds provide a structure similar to muscle extracellular matrix found in the body and show promising results in mimicking muscle architecture and encouraging new muscle fiber formation. However, the scaffolds alone do not fully restore regular muscle function, nor do they help regenerate other essential connections to the muscle such as the nervous system.

This research builds on our lab's scaffold technology by incorporating neural cells, which have been shown to promote muscle cell maturation and facilitate the formation of critical connections to the muscle. We differentiated rat neural stem cells into motor neurons and seeded them in our collagen scaffolds to test their viability. We looked at nuclei counts and axon growth of the neural cells which revealed the presence of developed neurons in the scaffold. By providing support for neuron viability in the 3D structure, we can begin to work toward a neural-muscle cell co-culture in the scaffold, enabling greater levels of myogenic regeneration as well as stronger neural connections than what is possible with the scaffold alone.