The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury

Many studies have described biomaterial devices (conduits and scaffolds) that can be implanted into experimental lesions and which support axonal growth. However, a disadvantage of such pre-formed devices is that tissue needs to be excised to allow their insertion. In this study we have therefore examined four biomaterials that can be injected into an injury site and which gel in situ; namely collagen, viscous fibronectin, fibrin, and fibrin + fibronectin (FB/FN). The materials were tested in an experimental knife-cut cavity in the rat spinal cord, and evaluated at 1 week and 4 weeks survival for their biocompatibility, neuroprotective efficacy, and permissiveness for axonal growth. At one week, all four materials showed good integration with the host spinal cord and supported some degree of axonal ingrowth, which was associated with infiltration of Schwann cells and deposition of laminin. However axon growth in the collagen implants was uneven because implants contained dense inclusions which were not penetrated by axons. At 4 weeks, axon growth was greatest in the fibronectin and FB/FN implants, however the fibronectin implants had large cavities at the interface between the implant and host spinal cord. The fibronectin implants also had fewer surviving neurons in the intact spinal cord adjoining the implant site. The FB/FN mixture thus had the best combination of properties in that it was easy to handle, integrated with the host spinal cord tissue, and supported robust growth of axons. It therefore has promise as an injectable biomaterial for filling cavities at spinal cord injury sites.