Peripheral Nerve Repair Using Tissue Engineered “Living Scaffolds” Comprised of Stretch-Grown Aligned Axonal Tracts Promotes Survival of Spinal Cord Motor Neurons

Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon stretch-growth. We have shown that TENGs effectively serve as living scaffolds to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axon-facilitated axon regeneration (AFAR), by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus non-living regenerative scaffolds in preserving host sensory and motor neuron cell health, using retrograde dye transport as a proxy, following bridging of segmental nerve defects. Rats were assigned across five groups: naive or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity. These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that when used to bridge segmental nerve defects, TENGs preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft), and therefore represent a promising alternative strategy for neurosurgical repair following PNI.