Injectable hydrogel materials for spinal cord regeneration: a review

Spinal cord injury (SCI) presents a complex regenerative problem due to the multiple facets of growth inhibition that occur following trauma to the cord parenchyma and stroma. Clinically, SCI is further complicated by the heterogeneity in the size, shape and extent of human injuries. Many of these injuries do not breach the dura mater and have continuous viable axons through the injury site that can later lead to some degree of functional recovery. In these cases, surgical manipulation of the spinal cord by implanting a preformed scaffold or drug delivery device may lead to further damage. Given these circumstances, in situ-forming scaffolds are an attractive approach for SCI regeneration. These synthetic and natural polymers undergo a rapid transformation from liquid to gel upon injection into the cord tissue, conforming to the individual lesion site and directly integrating with the host tissue. Injectable materials can be formulated to have mechanical properties that closely match the native spinal cord extracellular matrix, and this may enhance axonal ingrowth. Such materials can also be loaded with cellular and molecular therapeutics to modulate the wound environment and enhance regeneration. This review will focus on the current status of in situ-forming materials for spinal cord repair. The advantages of, and requirements for, such polymers will be presented, and examples of the behavior of such systems in vitro and in vivo will be presented. There are helpful lessons to be learned from the investigations of injectable hydrogels for the treatment of SCI that apply to the use of these biomaterials for the treatment of lesions in other central nervous system tissues and in organs comprising other tissue types.