Tissue Engineering for Nerve Regeneration

Abstract

Cut a peripheral nerve and leave a gap of more than three centimetres, and the surgeon faces an unpleasant choice. The textbook answer is an autologous nerve graft -- take a piece of sural nerve from behind the ankle, flip it around, and sew it into the gap. It works reasonably well, maybe 50 to 80 percent of patients recover useful function, but it leaves the donor site permanently numb and there is only so much sural nerve to harvest. For decades, tissue engineers have been trying to build a synthetic alternative: a tube you can pull off the shelf, suture into the gap, and expect the nerve to grow through. For short gaps the simple tubes work -- FDA-cleared collagen and PGA conduits handle defects up to about two centimetres without much trouble. But stretch that gap past three centimetres and the hollow tube fails, because the Schwann cells migrating inward from each stump run out of steam before they meet in the middle, and without Schwann cells the regenerating axons have nothing to grow along. Our group spent four years (2019-2023) testing every major strategy for fixing this problem: loading conduits with slow-release neurotrophic factors to coax the axons forward, seeding them with Schwann cells or fat-derived Schwann-like cells to provide biological support throughout the gap, spinning aligned polymer nanofibres to give axons a physical track to follow, and 3D-printing multi-channel conduits that match the branching anatomy of the native nerve. We tested 180 formulations in all -- 44 bare scaffolds, 38 growth-factor-loaded, 42 cell-seeded, 32 electrospun aligned, and 24 bioprinted -- in a standardised rat sciatic nerve model with a 15 mm critical gap, and scored each on five quality dimensions that we combined into the Nerve Regeneration Tissue Engineering Quality Index (NRTEQI). The index correlated with functional muscle recovery at r = +0.84 (AUC = 0.884), and the winners were conduits that combined all three enhancements -- aligned fibres plus Schwann cells plus GDNF microspheres -- which recovered 74.4 percent of normal muscle signal strength, statistically indistinguishable from the autograft benchmark of 78.4 percent.