Integrating Cells, Biomaterials, and Advanced Engineering for Next-Generation Peripheral Nerve Repair

Area of Science:

• Biomaterials Science
• Cell Biology
• Biofabrication

Background:

• Peripheral nerve injuries (PNIs) cause significant functional deficits, with autografts having limitations for long or proximal lesions.
• Engineered nerve conduits offer a promising alternative to autografts, leveraging advances in cell biology, biomaterials, and biofabrication.
• This review integrates these domains to establish a translational framework for engineered nerve replacements.

Purpose of the Study:

• To review the past decade of progress in engineered nerve conduits for PNI repair.
• To evaluate cell-based therapies, biomaterial scaffolds, and integrated strategies.
• To benchmark functional outcomes using standardized metrics and propose design-readiness targets.

Main Methods:

• Structured narrative review of 160 articles (2015-2025) from major scientific databases.
• Analysis of cell types (SCs, MSCs, iPSCs, NSCs/NPCs, OECs), scaffold materials (natural, synthetic, hybrid), and integrated constructs (seeded conduits, hydrogels, conductive designs, 3D bioprinted).
• Evaluation of functional recovery in rodent (≤15 mm) and large-animal (≥30 mm) models using motor (SFI, CMAP, NCV) and sensory metrics.

Main Results:

• Cell-seeded conduits achieve ≥85% motor recovery in rodent models and show promise in large animals for nerve gaps up to 30 mm.
• Various cell types and scaffold designs demonstrate potential for neurotrophic support, immunomodulation, and remyelination.
• Standardized sensory testing shows parallel recovery trends, though less frequently reported.

Conclusions:

• Engineered conduits are nearing equivalence with autografts for specific PNI models.
• Key challenges include vascularization, degradation by-products, cell variability, and scalable manufacturing.
• Clinical translation is promising for digital nerve repairs, with future potential for more complex injuries using advanced, integrated strategies.