Collagen Nerve Conduits and Scaffolds in Peripheral Nerve Repair: A Comprehensive Review with Meta-Analytical, Mechanical Failure Mapping, and AI-Driven Design Insights

Nervous system

Abstract

Peripheral nerve injuries (PNIs) affect millions worldwide annually, often resulting in persistent sensorimotor deficits. Autologous nerve grafting remains the clinical gold standard but is limited by donor site morbidity and limited availability [1, 2]. Collagen-based nerve guidance conduits (NGCs) offer excellent biocompatibility, low immunogenicity, and natural extracellular matrix (ECM) mimicry [3, 4]. This review provides three novel analytical layers: (1) a pooled analysis of 7 clinical studies (n=412) stratifying success rates by gap length, demonstrating decline from 92% in gaps <1 cm to 32% in gaps >3 cm (p<0.001 vs. autograft); (2) a predictive failure mode map identifying mechanical collapse, fibrotic encapsulation, and degradation-regeneration mismatch as dominant failure mechanisms; and (3) an artificial neural network (ANN)-based optimization framework for conduit design parameters. Genipin crosslinking at 0.1% concentration achieves optimal degradation kinetics (half-life ≈15.4 days) with relative cell growth rates of 87.9–105.4%, indicating very low cytotoxicity [5, 6]. Cost-effectiveness analysis confirms collagen conduits are favorable for gaps <2 cm (ICER 17,073/QALY) but marginal for gaps>3cm(ICER17,073/QALY)but marginal for gaps>3cm(ICER50,000/QALY). Collagen conduits are recommended for sensory nerve gaps <2 cm but are not recommended for gaps >3 cm or pure motor nerves. Next-generation conduits must become mechanically reinforced, smart, and AI-optimized.