Study On Hyaluronic Acid Based Scaffolds For Regeneration Of Spinal Cord And Facial Nerve Injury

Nervous system is one of the most complex systems in the human body. To achieve repair and regeneration after nerve injury, even functional recovery, is the goals of nerve tissue engineering. Hyaluronic acid, which is a major component of extracellular matrix in central nervous system, was chosen as the substrate of nerve tissue engineering scaffold. Hyaluronic acid based scaffolds have been modified with laminin, poly-D-lysine and Nogo receptor antibody in our laboratory before. These scaffolds with/without nerve stem cells were observed to promote nerve regeneration and some signs of functional recovery after implanting into the rats’brain injury sites. On this basis, hyaluronic acid was further changed by a variety of physical and chemical modifications, then explored the feasibility of these scaffolds in the promotion of the spinal cord and facial nerve repair.Scaffolds as cell carriers, should be conducive to cell adhesion and survival firstly, followed by promoting the cell function. Hyaluronic acid was modified with poly-L-lysine and Nogo receptor antibody together to improve two phases of the interactions between scaffolds and cells. This modified scaffold significantly enhanced the biocompatibility with the primary hippocampal neurons. In vivo experiments also showed that this scaffold had a better ability to promote spinal cord nerve regeneration compared with individual modified scaffolds, after implanting into the injury site of rat’s spinal cord.Scaffolds are also carriers of factors. The reaction between pure poly-lactic acid - glycolic acid microspheres and nerve cells had been studied, and no inhibition was found. In this thesis, the release behaviors of Nerve Growth Factor from poly(lactic-co-glycolic acid) microspheres and the combination between hyaluronic acid based scaffold and the microspheres were studied. This study provided a viable approach for hyaluronic acid based scaffold with multiple factors.To replace the extracellular matrix temporarily in the injury spinal cord, the design of scaffolds still needs to consider that the axons spread out along a specific orientation. It would be a rational strategy of guiding regenerated axons by simulating the structure of spinal cord, making it easier establish contact with the target site. Hyaluronic acid based scaffolds were synthesized with oriented pores by the gradient freeze-drying process. The effects of molecular chain to the oriented pores were studied, which was a useful exploration for the synthesis of ideal oriented pores in the future.The major inhibition of peripheral nerve injury is that the hyperplasia of surrounding tissue prevented the spontaneous axonal regeneration. In this study, hyaluronic acid based scaffold was filled into the collagen conduit, and combined with both neurotrophin-3 and neural stem cells for the repair of rabbit facial nerve injury. Histological and electrophysiological results indicated that this nerve conduit promoted the regeneration of rabbit facial nerve axon.