The loss of neurons and degeneration of axons after spinal cord injury result in the loss of sensory and motor functions. A bridging biomaterial construct that allows the axons to grow through has been investigated for the repair of injured spinal cord. Due to the hostility of the microenvironment in the lesion, multiple conditions need to be fulfilled to achieve improved functional recovery. A scaffold has been applied to bridge the gap of the lesion as contact guidance for axonal growth and to act as a vehicle to deliver stem cells in order to modify the microenvironment. Stem cells may improve functional recovery of the injured spinal cord by providing trophic support or directly replacing neurons and their support cells. Neural stem cells and mesenchymal stem cells have been seeded into biomaterial scaffolds and investigated for spinal cord regeneration. Both natural and synthetic biomaterials have increased stem cell survival in vivo by providing the cells with a controlled microenvironment in which cell growth and differentiation are facilitated. This optimal multi‒disciplinary approach of combining biomaterials, stem cells, and biomolecules offers a promising treatment for the injured spinal cord.

Introduction: Microspheres fabricated from natural materials serve as a promising biodegradable and biocompatible carrier in a small volume for efficient cell delivery to the lesion of the injured neural tissue to generate biological functions. As the major component of extracellular matrix and due to its natural abundance within the body, collagen may be fabricated into microspheres and improve the ability of pre-seeded cells on the microspheres to encounter the hostile micro-environment in the lesion. Methods: In this study, collagen microspheres were fabricated using the water-in-oil emulsion technique and cross-linked with 1-ethyl-3-(3-dimethylaminopropryl) carbodiimide. Oligodendrocyte progenitor cells isolated from postnatal day P1 to 2 rats were cultured and differentiated on the microspheres. The microspheres carrying the oligodendrocyte progenitor cells were co-cultured with dorsal root ganglions from 15-day-old rat embryos. The myelination formation was studied for the co-culture of oligodendrocyte progenitor cells and dorsal root ganglions. Results: We showed that the viability of oligodendrocyte progenitor cells, B104 cells and PC12 cells grown on microspheres was not significantly different with those in cell culture plates. Oligodendrocyte progenitor cells differentiated into oligodendrocytes on collagen microspheres. The oligodendrocytes grown on microspheres extended processes that wrapped the axons of dorsal root ganglion neurons and the formation of myelin sheath was observed in the co-culture. Conclusions: This study demonstrates the feasibility of collagen microspheres in further applications for the delivery of neural progenitor cells for neural regeneration.