5 cm Gap Injury Repair: Growth Factor Support And Functional Analysis In A Rabbit Common Peroneal Nerve Model

Abstract

Nerve conduits have shown to successfully bridge nerve gaps of ≤ 3 cm; however repair of longer, mixed or motor nerve gaps still remains a clinical challenge. In order to study regeneration techniques in clinically relevant long gaps, larger animal models are required. Standardized methods to evaluate functional outcome are necessary to clinically translate experimental treatments. In this study, the capability of the biodegradable and transparent cross-linked doped polyester elastomer (CUPE) to serve as a nerve conduit material in a multiluminal nerve conduit across a 5 cm gap in a rabbit common peroneal nerve model was evaluated. The effect of growth promoting factor, pleiotrophin released from microparticles and from fibers within a synthetic multiluminal conduit in bridging a 5 cm long gap, was also investigated. Functional outcome was analyzed using toe spread, sensory parameters, force and muscle weights at the end of twelve weeks in the injured and uninjured hindlimbs of each rabbit. Qualitatively CUPE demonstrated better function than polyurethane in supporting the structure of agarose microchannels, however histological analysis revealed no axonal regeneration across the gap in any of the conduits. This summarizes the results of the first two aims. Variance in gait pattern is one of the most significant observations after peripheral nerve injury Video gait analysis, together with joint kinematics, was used to characterize the gait and ankle angle changes in the injured rabbits during treadmill locomotion. Foot drop, exaggerated knee flexion characteristic of peroneal injury was observed. In summary, this pilot study revealed the necessity of regenerative substrate and trophic support across a 5 cm long gap, established the changes in kinematic parameters after peroneal nerve injury in a rabbit model.