Researchers have made significant strides in developing biomaterials for nerve guiding conduits, exploring natural polymers like chitosan, collagen, and silk, along with synthetic counterparts such as silicone, poly(lactic-co-glycolic acid), polycaprolactone, and poly(L-lactic acid). Each material offers distinct benefits, necessitating further study for refinement. Diverse conduit designs, including hollow/non-porous, porous, grooved, multi-channel, and fiber/hydrogel-filled conduits, have been created. Multi-channel and aligned fiber designs stand out for providing effective topographical cues guiding axon formation. Various manufacturing methods, from solvent casting to three-dimensional printing techniques like electrohydrodynamic jet and digital light processing, enable scaffold manipulation. Positive outcomes in laboratory (in vitro) and live animal (in vivo) experiments indicate the effectiveness of biomaterial-based conduits in connecting nerve gaps and promoting regeneration. However, research remains predominantly in the preclinical phase, with challenges like inadequate mechanical characteristics and the absence of biological signals. Addressing these constraints requires material refinement and the introduction of biological functionality. Future prospects involve intelligent conduits using nanocomposite biomaterials, stem cells, controlled release of neurotrophic factors, and integration of electrical and optical stimulation. Comprehensive preclinical validation is crucial before clinical translation. Despite advancements, further study is essential to fully leverage biomaterials as nerve autograft substitutes, with multidisciplinary collaboration key to continued progress in this promising field. The main goal is to present a thorough overview of the most recent developments, cutting-edge research gaps, and future prospects in the engineering and design of biomaterial-based nerve guiding conduits for the repair of peripheral nerve injury.
