Carbon Nanodot-enabled Fluorescent Nerve Conduits for Peripheral Nerve Repair: A Systematic Review of Translational...

This systematic review evaluates the translational readiness of carbon nanodot (CD)-enabled nerve conduits within the broader context of peripheral nerve repair. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology, major databases were searched through January 2025 for clinical, preclinical, biomaterial, imaging, degradation, and economic studies related to autograft, allograft, conduit repair, CDs, and fluorescence-guided nerve visualization. Sixty-eight studies met the inclusion criteria. CD-containing conduits, including fruit-peel-derived systems, have demonstrated tunable fluorescence, neural-range conductivity, and favorable Schwann cell and axonal responses but remain limited to small-animal proof-of-concept models, without good laboratory practice toxicology, large-animal studies, investigational device exemption-enabling data, or human trials. In contrast, fluorescence-guided nerve imaging with near-infrared agents and nerve autofluorescence is already clinically validated under standard operating room lighting, defining target emission windows and signal-to-background thresholds for future CD-based scaffolds. CDs undergo enzyme-mediated biodegradation and can be immobilized within hydrogels for controlled, degradation-linked release; however, their long-term in vivo fate and mass balance remain incompletely characterized. Across studies, CD synthesis is hindered by major reproducibility and quality-control gaps in quantum yield, particle size, and surface chemistry. Economic analyses highlight substantial donor-site morbidity and operative time costs for autografts, a lack of transparent device-level pricing for allografts and conduits, and preliminary evidence of cost-effectiveness advantages for allografts over nonoperative management. Overall, CDs are scientifically promising but translationally immature compared with established passive conduits, and targeted advances in manufacturing, safety, imaging performance, and economic evaluation will be required for clinical adoption.