Clinical translation of protein-engineered, matrix-mimetic nerve guidance conduits for peripheral nerve injury

Abstract

Due to poor regeneration in the peripheral nervous system, injury often results in chronic or permanent loss of motor function and sensation. Several nerve guidance conduits (NGCs) are available in the clinic to aid in peripheral nerve regeneration, including naturally-derived acellular nerve allografts and synthetic hollow nerve guidance conduits. However, despite the ~200,000 surgeries performed each year in an attempt to regain lost function, many of which utilizes these NGCs, less than 25% of patients recover appropriate motor control and less than 3% regain full sensation.

To address this clinical need, we propose the development of a NGC composed of an engineered protein hydrogel (eNGC) which combines the reproducible and reliable fabrication of synthetic NGCs with the biochemical matrix cues of naturally-derived NGCs known to be critical in regeneration. Our eNGCs are composed of a modular, engineered recombinant protein that has independently tunable biochemical and biomechanical cues, allowing the optimized presentation of multiple matrix cues to mimic the native extracellular matrix. This allows our eNGC to better emulate the complexity of the native nerve matrix within a synthetic, reproducible material.