The Role of Collagen in Peripheral Nerve Regeneration and Emerging Repair Strategies.

Abstract

To our knowledge, no comprehensive review has specifically examined the role of collagen in peripheral nerve regeneration. Peripheral nerve injuries are associated with substantial impairment and incomplete recovery despite advances in microsurgical repair. Outcomes are limited by donor-site morbidity, graft mismatch, and the biological complexity of nerve degeneration and regeneration. Collagen, a major component of the extracellular matrix, plays an important regulatory role in this process and has emerged as a promising biomaterial for nerve repair. This review examines the biological role of collagen in peripheral nerve regeneration and evaluates current collagen-based repair strategies in the literature. The discussion focuses on how collagen helps coordinate regenerative response after injury by shaping the extracellular environment, supporting key cellular interactions, and guiding axonal recovery. We conducted a literature review of articles on collagen, peripheral nerve regeneration, and nerve repair using the PubMed and Web of Science databases. Collagen was found to be a versatile protein that plays an important role in regenerative microenvironments. As a key extracellular matrix component, it supports Schwann cell adhesion, migration, and alignment, helping to organize the extracellular framework that is required for axonal regrowth and remyelination. Dysregulated collagen deposition can contribute to fibrosis, scar formation, neuroma development, and impaired regeneration. Findings suggest that collagen-based conduits, hydrogels, scaffolds, and decellularized nerve grafts can potentially support peripheral nerve repair by recreating key structural and biochemical features. These biomaterials offer advantages such as biocompatibility and biodegradability, though limitations remain in mechanical strength, degradation timing, and effectiveness in larger nerve gaps. Collagen plays a central role in both native peripheral nerve regeneration and the development of emerging repair technologies. Future advances in collagen-based biomaterials may strengthen clinical translation and improve functional outcomes after peripheral nerve injury.