Recombinant Biomaterials for Treatment of Spinal Cord Injuries

Approximately 15,000 new spinal cord injuries (SCI) occur in the US each year, primarily affecting young adults. Schwann cells are a promising therapy for SCI and are currently being explored in clinical trials; however, significant limitations in cell delivery and long-term survival decrease their therapeutic potential. The low cell retention post-transplantation is partly attributed to (i) mechanical forces during injection that damage the cell membrane and (ii) the lack of a three-dimensional (3D) matrix to support cell viability post-injection. We hypothesized that the development of a shear thinning, injectable hydrogel would improve cell viability, engraftment, and regenerative capacity after transplantation. This hydrogel, produced from a blend of engineered recombinant proteins and peptide-modified synthetic polymer is termed SHIELD: Shear-thinning Hydrogel for Injectable Encapsulation and Long-term Delivery. SHIELD formulations with storage moduli, G', spanning 10-500 Pa all showed excellent viability of encapsulated Schwann cells (>98%) and significant mechanical protection from membrane damage when exposed to syringe needle flow. After 7 days in vitro, 3D cultures of within all SHIELD formulations showed positive immunostaining for Schwann cell markers (p75, S100), but cultures in formulations of intermediate stiffness showed higher proliferation rates and decreased caspase activity. In a rat cervical contusion model of SCI, Schwann cells delivered in SHIELD resulted in smaller lesion volumes and improved functional outcomes compared to cells delivered in saline and injury control groups. Since even a mild functional recovery would mean a vast quality-of-life improvement for SCI patients, developing a regenerative therapy for SCI would be extremely significant clinically.