Three-Dimensional Printing of the Epineurium for Peripheral Nerve Repair: A Comprehensive Review of Novel Scaffolds...

Background: Nerve conduits are used to bridge peripheral nerve defects caused by trauma, iatrogenic injury, or oncologic disruption. Three-dimensional (3D) biomimetic scaffolds for peripheral nerve regeneration have advanced significantly in recent years, driven by improvements in printing technology and neuronal seeding techniques. We report on published designer conduits that can recreate the epineurium, a critical yet challenging-to-manufacture feature of nerve tissue. Methods: A medical librarian conducted a literature search for our systematic review on EMBASE, Web of Science, and PUBMED, following PRISMA guidelines, for articles from January 2010 to January 2026 for the systematic review. Descriptive statistical analysis was performed using Microsoft 365 Suite software. The literature review was conducted using keywords and search terms describing the history and development of 3DP nerve guidance conduits published prior to January 2026. Results: Our search yielded 273 titles, of which 8 were included after full-text review; these studies used 3D printing to generate nerve conduits for preclinical models. Manual data extraction identified studies reporting successful epineurial recreation. The included scaffold materials were polycaprolactone, poly(l-lactide-co-ε-caprolactone), poly(lactic-co-glycolic acid), acrylate resin, and gelatin methacryloyl. In animal model studies, various terms were used to describe the epineurium outer sheath. Despite this variability in nomenclature, many of these reports indicated successful sciatic functional index (SFI) recovery, favorable g-ratios, good durability, high cell viability, and significant neurite elongation at the time of sacrifice. Conclusions: 3DP nerve conduits targeting the epineurium are promising approaches for treating peripheral nerve defects. The constructs promote oriented growth and myelination. Future research on incorporating the epineurium into nerve scaffolds may consider encapsulating NGF to promote more efficient nerve regeneration, standardizing the definition of epineurial recreation, designing mechanical and permeability reporting benchmarks, and evaluating cell strategies using comparable functional and histologic endpoints.