| Abstract: | Nerve defects are challenging to address clinically without satisfactory treatments. As a reliable alternative to autografts, decellularized nerve matrix scaffolds (DNM‐S) have been widely used in clinics for surgical nerve repair. However, DNM‐S remain inferior to autografts in their ability to support nerve regeneration for long nerve defects. In this study, we systematically and clearly presented the nano‐architecture of nerve‐specific structures, including the endoneurium, basement membrane and perineurium/epineurium in DNM‐S. Furthermore, we modified the DNM‐S by supplementing decellularized nerve matrix hydrogel (DNMG) and glial‐derived neurotrophic factor (GDNF) and then bridged a 50‐mm sciatic nerve defect in a beagle model. Fifteen beagles were randomly divided into three groups (five per group): an autograft group, DNM‐S group and GDNF‐DNMG‐modified DNM‐S (DNM‐S/GDNF@DNMG) group. DNM‐S/GDNF@DNMG, as optimized nerve grafts, were used to bridge nerve defects in the same manner as in the DNM‐S group. The repair outcome was evaluated by behavioural observations, electrophysiological assessments, regenerated nerve tissue histology and reinnervated target muscle examinations. Compared with the DNM‐S group, limb function, electrophysiological responses and histological findings were improved in the DNM‐S/GDNF@DNMG group 6 months after grafting, reflecting a narrower gap between the effects of DNM‐S and autografts. In conclusion, modification of DNM‐S with DNMG and GDNF enhanced nerve regeneration and functional recovery, indicating that noncellular modification of DNM‐S is a promising method for treating long nerve defects. |
