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Peripheral nerve injuries are a common and difficult clinical problem worldwide with a steadily increasing incidence in recent years,affecting about 3% of trauma patients.These injuries result in partial or total impairment of motor,sensory,and autonomic functions in the involved segments of the body.Severe injuries that form a large nerve gap between the proximal and distal nerve stumps may cause life-long disability,impact the patients quality of life,and constitute significant social and economic burdens.The current gold standard for surgical treatments is autografting,namely bridging the nerve gap with autologous nerve grafts which are harvested from another site in the body.Because of inevitable drawbacks associated with autografting—mainly the limited supply of donor nerves,donor site morbidity,and secondary deformities—the development of artificial substitutes for autologous nerve grafts is a pressing need in the field of regenerative medicine.Tissue engineering has proven to be helpful at fulfilling this important task.We previously demonstrated that a natural and biodegradable polysaccharide,chitosan,was biocompatible with neuroglial cells by virtue of its positive effects on the adhesion,survival,migration,and proliferation of Schwann cells.We also demonstrated that the in vivo biodegradation product of chitosan,chitooligosaccharide,could support neural cell adhesion and encourage neuronal differentiation and neurite outgrowth through the up-regulation of neurofilament and N-cadherin expression.We fabricated chitosan-based nerve grafts,using an injection molding method,which were composed of a chitosan conduit filled with polyglycolic acid (PGA) filaments.These nerve grafts were used to bridge a 30 mm long sciatic nerve gap in dogs.Six months later,the results showed that the injured nerve trunk was reconstructed with restoration of nerve continuity and axonal functions such as electrical conduction and axoplasmic transport.Further,the target muscles were re-innervated with improvements in the locomotor activity of the injured limb,while the nerve graft had been completely degraded and absorbed by the body.Other nerve grafts constructed with the same methods were also used to bridge a long-term delayed sciatic nerve gap in rats,and experimental observations confirmed the possibility of using chitosan-based nerve grafts for such repairs.Our chitosan-based nerve graft invention has been patented in China.With approval from the Chinese State Food and Drug Administration (SFDA) for the use of chitosan-based nerve grafts in clinical trials,we have launched a prospective randomized controlled multicenter study in four Chinese public hospitals.Two human case studies have been reported,in which 30 and 35 mm long median nerve gaps were repaired with chitosan-based nerve grafts.The three-year follow-up indicated that overall motor and sensory function of both patients injured nerves had recovered to M4 or S3* levels,according to British Medical Research Council (MRC) grading scale.