Grants We Funded

Abstract
Peripheral nerve injuries represent a significant source of morbidity and disability in the United States and abroad. When end-to-end repair is not possible, autologous nerve grafting remains the preferred method for reconstruction of nerve gaps. Such grafts are typically taken from superficial sensory nerves, such as the medial antebrachial cutaneous or sural nerves, in an effort to minimize donor-site morbidity. Though sensory nerves have long been assumed to be a suitable substrate for motoneuron regeneration, the limited functional recovery achieved with grafting compared to end-to-end repair suggests otherwise. A growing body of experimental evidence suggests that axonal regeneration improves when motor nerve gaps are reconstructed with motor grafts, and likewise for sensory. Termed modality-specific regeneration (MSR), this phenomenon seems to challenge the existing clinical dogma of repairing motor defects with sensory grafts. However, previous experiments demonstrating MSR utilized nerve grafts constructed of multiple cables or taken from spinal roots, which are not representative of nerve reconstructions performed in human patients. In our proposed study, we seek to demonstrate MSR in a more clinically relevant scenario. We hypothesize that matching of motor or sensory modality between donor and recipient nerves results in enhanced axonal regeneration. In order to more closely replicate nerve grafting as performed in human patients, our study will utilize only single-cable peripheral nerve grafts without the use of spinal roots. Our design also incorporates a more extensive analysis of grafted nerves than in prior studies, including retrograde labeling, stereology, and electron microscopy. If borne out by this study, modality matching of nerve grafts has the potential to significantly alter the practice of peripheral nerve reconstruction and enhance the clinical outcomes achieved in the nerve-injured patient.