Understanding how nerves spontaneously innervate tissues or regenerate small injuries is critical to enhance material-based interventions to regenerate large scale, traumatic injuries. During embryogenesis, neural and vascular tissues form interconnected, complex networks as a result of signaling between these tissue types. Here, we report that human endothelial cells (HUVECs) secrete brain-derived neurotrophic factor (BDNF), which significantly stimulated axonal growth from chicken or rat dorsal root ganglia (DRGs). HUVEC-conditioned medium was sufficient to enhance axonal growth, demonstrating that direct cell-cell contact was not required. When BDNF was neutralized, there was a significant reduction in axonal growth when incubated in HUVEC-conditioned medium and in direct co-culture with HUVECs. These data show that HUVECs secrete neurotrophic factors that significantly enhance axonal growth, and can inform future in vivo studies to direct or pattern the angiogenic response in regenerating tissues to encourage re-innervation.

Volumetric muscle loss is a traumatic injury which overwhelms the innate repair mechanisms of skeletal muscle and results in significant loss of muscle functionality. Tissue engineering seeks to regenerate these injuries through implantation of biomaterial scaffolds to encourage endogenous tissue formation and to restore mechanical function. Many types of scaffolds are currently being researched for this purpose. Scaffolds are typically made from either natural, synthetic, or conductive polymers, or any combination therein. A major criterion for the use of scaffolds for skeletal muscle is their porosity, which is essential for myoblast infiltration and myofiber ingrowth. In this review, we summarize the various methods of fabricating porous biomaterial scaffolds for skeletal muscle regeneration, as well as the various types of materials used to make these scaffolds. We provide guidelines for the fabrication of scaffolds based on functional requirements of skeletal muscle tissue, and discuss the general state of the field for skeletal muscle tissue engineering.

Skeletal muscle injuries that occur from traumatic incidents, such as those caused by car accidents or surgical resections, or from injuries sustained on the battlefield, result in the loss of functionality of the injured muscle. To understand skeletal muscle regeneration and to better treat these large scale injuries, termed volumetric muscle loss (VML), in vivo injury models exploring the innate mechanisms of muscle injury and repair are essential for the creation of clinically applicable treatments. While the end result of a muscle injury is often the destruction of muscle tissue, the manner in which these injuries are induced as well as the response from the innate repair mechanisms found in muscle in each animal models can vary. This targeted review describes injury models that assess both skeletal muscle regeneration (i.e., the response of muscle to myotoxin or ischemic injury) and skeletal muscle repair (i.e., VML injury). We aimed to summarize the injury models used in the field of skeletal muscle tissue engineering, paying particular attention to strategies to induce muscle damage and how to standardize injury conditions for future experiments.