Building the Regenerative Microenvironment with Functional Biomaterials for Spinal Cord Injury Repair

Spinal cord injury (SCI) is a devastating injury resulting in changes in the spinal cord’s motor, sensory, or autonomic functions. Following SCI, an inhibitory environment develops at the injury site for neural regeneration. In this review, we summary the strategies to rebuild the regenerative microenvironment with functional biomaterials for SCI repair mainly based on our research. We have developed a functional biomaterial consisting of collagen scaffolds and biologically active molecules (neurotrophic factor or the antagonists to myelin-associated inhibitor), and stem cells to rebuild a nerve regeneration microenvironment. Specifically, (1) the linear ordered collagen scaffold (LOCS) was used to guide the neural regeneration along its fibers and decrease the formation of glial scars, (2) collagen binding neurotrophic factors were incorporated into the scaffolds to promote neuronal survival and neural fiber regeneration, (3) antagonists to myelin-associated inhibitors were added to the scaffold to direct the neuronal differentiation of the native or transplanted neural stem cells at the injury site, (4) mesenchymal stem cells (MSCs) were also added to the scaffold to reduce the acute inflammatory response due to SCI. These strategies were found to promote neural regeneration and functional recovery in SCI animals. In addition, the endogenous neural stem cells (NSCs) or implanted NSCs could be differentiated into neurons, which re-established the neuronal circuits to improve SCI repair under the favorable environment.