Inhibition of RGD-modified composite nerve conduit on traumatic neuroma formation

摘要

Peripheral nerve injury is the common cause that leads to disability. Large nerve defect and traumatic neuroma are two main bottleneck problems during repairing after peripheral nerve injury. So far, the mechanism of neuroma development and progression are still unclear, and there is very limited research on neuroma inhibition with nerve conduit. Our group previously found that a PDLLA/PRGD/β-TCP composite conduit had beneficial effect on nerve regeneration, and no obvious neuroma formation was found in around 300 experimental animals. The main mechanism of neuroma formation is based on excessively sedimentary collagen proliferation. We hypothesize that POLLA/PRGD/β-TCP composite have the effect on the neural scar formation-related cytokines such as NGF, IFN-y etc., matrix metallo-proteinases, gene expression and protein level of collagen. The effect of the conduit on neural scar distribution and scar ratio, nerve function recovery, structure of regenerated myelin sheath have been studied. In vitro test, PRGD/PDLLA/β-TCP membranes showed better cytocompatibility with Schwann cells. Testing in vivo demonstrated that PRGD/PDLLA/β-TCP conduits can effectively promote axonal regeneration of 10mm rat sciatic nerve defect, which is close to the success of autograft. After an observation period of 1 month, PRGD/PDLLA/β-TCP conduit-implanted showed no neuroma and significantly improving on the neurophysiological and neuropathological levels compared with the PDLLA conduit as control group. The microenvironment of the inner conduit, containing an appropriate concentration of calcium ion, growth factors and immunologic factors, played an important role in the inhibition of neuroma formation. The neural scar distribution is perineural scarring and the scar ratio is lower than the control of PDLLA group. The study revealed that PRGD/PDLLA/β-TCP conduits promoted nerve regeneration and inhibits neuroma formation. It is going to provide experimental basis for future studies in nerve conduits for inhibition of neuroma formation and promoting long-distance nerve regeneration as well as the clinical therapy for neuroma.