Background. Spinal cord injury (SCI) presents to the clinic as complete, incomplete or compressive. SCI patients also display varying quantities of spinal cord tissue damage or loss. One theory proposed to repair the injured spinal cord and regain motor control is to regenerate axons through the lesion site. Current methods proposed to increase neuroregeneration following SCI include; preserving spared neuronal tissue, increasing axonal regeneration, reducing inflammation, reducing glial scar formation and methods aimed at bridging the lesion gap to facilitate the transmittance of physical cues and provide a platform for neuronal sprouting and functional recovery. Objective. This study was designed to quantify the impact of a local injectable in situ forming hydrogel reservoir therapy following rat hemisection SCI. Method. Our group investigated the effect of hydrogel only treatment following SCI in addition to hydrogels loaded with a neuronal growth factor, Neurotrophin-3 (NT-3), immediately following SCI. Functional recovery, assessed by Basso Beattie Bresnahan (BBB), and local healing mechanism, including neuronal regeneration, neuronal survival, glial scar formation, inflammation, astrocytosis, and collagen deposition were investigated one and six weeks post-surgery. Results. Delivery of an injectable hydrogel increased functional recovery, reduced inhibitory glial scarring and reducing inflammation at the injury site. Similarly hydrogel + NT-3 delivered directly into the injury site reduced glial scarring and collagen deposition resulting in increased neuronal survival across the lesion site. Conclusion. This study represents a novel and effective therapy combining growth factor and a biomaterial based therapy following SCI.

Traumatic spinal cord injury (SCI) results in disruption of tissue integrity and loss of function. We hypothesize that glycosylation has a role in determining the occurrence of regeneration and that biomaterial treatment can influence this glycosylation response. We investigated the glycosylation response to spinal cord transection in Xenopus laevis and rat. Transected rats received an aligned collagen hydrogel. The response compared regenerative success, regenerative failure, and treatment in an established nonregenerative mammalian system. In a healthy rat spinal cord, ultraperformance liquid chromatography (UPLC) N-glycoprofiling identified complex, hybrid, and oligomannose N-glycans. Following rat SCI, complex and outer-arm fucosylated glycans decreased while oligomannose and hybrid structures increased. Sialic acid was associated with microglia/macrophages following SCI. Treatment with aligned collagen hydrogel had a minimal effect on the glycosylation response. In Xenopus , lectin histochemistry revealed increased levels of N -acetyl-glucosamine (GlcNAc) in premetamorphic animals. The addition of GlcNAc is required for processing complex-type glycans and is a necessary foundation for additional branching. A large increase in sialic acid was observed in nonregenerative animals. This work suggests that glycosylation may influence regenerative success. In particular, loss of complex glycans in rat spinal cord may contribute to regeneration failure. Targeting the glycosylation response may be a promising strategy for future therapies.

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