Axonal regeneration into acellular nerve grafts is enhanced by degradationof chondroitin sulfate proteoglycan

Although the peripheral nerve has the potential to regenerate after injury, degenerative processes may be essential to promote axonal growth into the denervated nerve. One hypothesis is that the nerve contains growth inhibito rs that must be neutralized after injury for optimal regeneration. In the p resent study, we tested whether degradation of chondroitin sulfate proteogl ycan, a known inhibitor of axon growth, enhances the growth-promoting prope rties of grafts prepared from normal donor nerves. Excised segments of rat sciatic nerve were made acellular by freeze-killing before treatment with c hondroitinase ABC. Chondroitinase-dependent neoepitope immunolabeling showe d that chondroitin sulfate proteoglycan was thoroughly degraded throughout the treated nerve segments. In addition, neuronal cryoculture assays reveal ed that the neurite-promoting activity of acellular nerves was significantl y increased by chondroitinase treatment. Control and chondroitinase-treated acellular nerves were then used as interpositional grafts in a rat nerve i njury model. Axonal regeneration into the grafts was assessed 4 and 8 d aft er implantation by growth-associated protein-43 immunolabeling. At both tim e points, the number of axons regenerating into acellular grafts treated wi th chondroitinase was severalfold greater than in control grafts. Growth in to the chondroitinase-treated grafts was pronounced after only 4 d, suggest ing that the delay of axonal growth normally associated with acellular graf ts was attenuated as well. These findings indicate that chondroitinase trea tment significantly enhanced the growth-promoting properties of freeze-kill ed donor nerve grafts. Combined with the low immunogenicity of acellular gr afts, the ability to improve axonal penetration into interpositional grafts by preoperative treatment with chondroitinase may be a significant advance ment for clinical nerve allografting.