Porous Decellularized Nerve Grafts Facilitate Recellularization and Nerve Regeneration in a Rat Model of Critical Long‐Gap Peripheral Nerve Injury

Severe peripheral nerve injury (PNI) requiring nerve graft remains a clinical challenge due to limitations associated with currently available grafts. While decellularized nerve grafts (DNGs) are commonly used, their efficacy is largely restricted to short-gap repairs due to their acellular and dense structure, which poses a persistent challenge in the treatment of critical long-gap nerve defects. It is hypothesized that making porous DNGs (PDNGs) can create a suitable microenvironment that would facilitate the cell infiltration, recellularization, and further axonal growth to enhance nerve regeneration. In this study, PDNGs are generated and their ability are evaluated to support cell proliferation and penetration in vitro. Their potential to promote nerve regeneration in vivo using a rat model of sciatic nerve transection followed by implantation of a 30 mm-long graft is further evaluated. It is found that PDNGs facilitated greater cellular infiltration within the grafts and enhanced angiogenesis compared to the traditional compact DNGs. In vivo analysis further reveals thicker myelin sheaths in the PDNG group, along with improved axonal alignment. Taken together, PDNGs enhanced nerve regeneration by reorganizing the porous structure into an extracellular matrix that supported cell infiltration, revascularization, and remyelination, all of which contribute to nerve repair.