TY - JOUR T1 - Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair JF - bioRxiv DO - 10.1101/847988 SP - 847988 AU - Joseph C. Maggiore AU - Justin C. Burrell AU - Kevin D. Browne AU - Kritika S. Katiyar AU - Franco A. Laimo AU - Zarina S. Ali AU - Hilton M. Kaplan AU - Joseph M. Rosen AU - D. Kacy Cullen Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/22/847988.abstract N2 - 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, or “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 neuronal health following nerve repair. Rats were assigned across five groups: naïve, 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 TENGs may 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.HIGHLIGHTSTENGs preserve host spinal cord motor neuron health and regenerative capacity acutely following repair of segmental nerve defects, matching that of the clinical gold-standard autograft and exceeding commercially-available nerve guidance tubes.TENGs facilitated regeneration across segmental nerve defects, yielding similar degree of chronically surviving host spinal motor neurons and functional recovery as compared to autografts.Early surgical intervention for segmental nerve defect with living scaffolds, such as TENGs and autografts, preserves the host regenerative capacity, and likely increases the ceiling for total regeneration and functional recovery at chronic time points compared to (acellular) commercially-available nerve guidance tubes.TENGs preserve host neuronal health and regenerative capacity without sacrificing an otherwise uninjured nerve, and therefore represent a promising alternative strategy to autografts or nerve guidance tube repairs.Competing Interest StatementD.K.C is a co-founder and K.S.K. is currently an employee of Axonova Medical, LLC, which is a University of Pennsylvania spin-out company focused on translation of advanced regenerative therapies to treat nervous system disorders. Multiple patents relate to the composition, methods, and use of tissue engineered nerve grafts, including U.S. Patent 9,895,399 (D.K.C.), and U.S. Provisional Patent 62/569,255 (D.K.C). No other author has declared a potential conflict of interest. ER -