A Strategy Toward Bridging a Complete Spinal Cord Lesion Using Stretch-Grown Axons.

ABSTRACT

In this study, we evaluated the ability of stretch-grown tissue-engineered nerve grafts (TENGs) to perform as a living scaffold for axonal regeneration across a severed spinal cord lesion. TENGs, consisting of stretch-grown axons spanning two populations of dorsal root ganglia neurons, have proven to be effective in bridging gaps in peripheral nerve injury. A complete transection was performed at the thoracic level in a rodent model and 5 mm of cord was completely removed. TENGs encapsulated in a collagen hydrogel were placed within the cavity and compared against a collagen only transplant. Through hematoxylin and eosin (H&E) staining and immunohistochemistry, we found that TENGs survived up to 6 weeks post-transplant, extending neuronal processes into and through host tissue early on in both the rostral and caudal direction. In several cases, TENG axons penetrated into and through glial scar tissue, appearing to overcome a common obstacle for axonal regeneration in spinal cord injuries (SCIs). H&E staining also provided evidence that animals treated with TENGs resulted in lesion sites with greater tissue infiltration and less compression than animals treated with a collagen hydrogel only, an encouraging finding given the severity of the injury model. We also observed effects the TENGs had on glial scar formation, cyst formation, and immune response at multiple time points as these are common difficulties faced in tissue engineering methods to treat or repair SCI. If able to address these universal challenges associated with SCI, TENGs may offer an alternative option in neural transplantation and may represent a viable tool in the multifaceted treatment of SCI. Impact statement In complete spinal cord injury (SCI), a significant gap forms in the injury sites replacing the neural connections and limiting the link between healthy spinal cord distal to the injury and cerebral cortex. This study aims to demonstrate the potential benefit of hydrogel collagen constructs bearing stretch-grown dorsal root ganglion axons to bridge a complete injury gap, to restore the lost connections and forming a basic infrastructure to support the regrowth of new connection. This application of stretch-grown axons in neural implants offers hope to achieve a highly modifiable and resilient bridging strategy to treat SCI.