Aligned fibrous scaffolds containing glycosaminoglycan mimetics enhance Schwann cell-supported axon growth and myelination.

Abstract

Traumatic spinal cord injury causes functional impairments in large part due to the limited ability of damaged axons to regenerate. During development, the extracellular matrix (ECM) plays a critical role in providing molecular cues that promote and direct axon growth. Biomaterials that mimic the physicochemical properties of the ECM may be promising for promoting axon growth in the injured spinal cord. Glycosaminoglycans (GAGs) in the ECM during development are known to direct axon growth and guidance. We previously reported that GAG-mimetic cellulose sulfate, which can be synthesized with varying degrees of sulfation, partially and fully sulfated cellulose (pCelS and fCelS, respectively), promoted neurite extension over native GAGs. The present study investigated the use of GAG-mimetic containing scaffolds as a platform for Schwann cell (SC) transplants to promote axon growth. The aligned fibrous scaffolds consisted of gelatin or gelatin blended with polycaprolactone (PCL), in order to improve hydrolytic stability, with 0.25 wt.% GAG-mimetics. Our results demonstrated that the fCelS-containing scaffolds with SCs promoted more axon growth than the pCelS-containing scaffolds and the greatest myelination over all other scaffolds. Also, in the presence of astrocytes, fCelS-containing scaffolds supported axon growth. Furthermore, the fCelS-containing scaffolds were capable of binding and retaining a greater amount of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3 as compared to all other scaffolds. Aligned fibrous GAG-mimetic scaffolds containing fully sulfated cellulose may hold promise to repair damaged spinal cord tissue by providing physiochemical axon growth-promoting cues and a transplantation platform for SCs to support axon growth and myelination.