Preparation and assessment of an optimized multichannel acellular nerve allograft for peripheral nerve regeneration

Abstract

Peripheral nerve regeneration after injury is still a clinical problem. The application of autologous nerve grafting, the gold standard treatment, is greatly restricted. Acellular nerve allografts (ANAs) are considered promising alternatives, but they are difficult to achieve satisfactory therapeutic outcomes, which may be attributed to their compact inherent ultrastructure and substantial loss of extracellular matrix (ECM) components. Regarding these deficiencies, this study developed an optimized multichannel ANA by a modified decellularization method. These innovative ANAs were demonstrated to retain more ECM bioactive molecules and regenerative factors, with effective elimination of cellular antigens. The presence of microchannels with larger pore size allowed ANAs to gain higher porosity and better swelling performance, which improves their internal ultrastructure. Their mechanical properties were more similar to those of native nerves. Moreover, the optimized ANAs exhibited good biocompatibility and possessed significant advantages in supporting the proliferation and migration of Schwann cells in vitro. The in vivo results further confirmed their superior capacity to promote axon regrowth and myelination as well as restore innervation of target muscles, leading to better functional recovery than the conventional ANAs. Overall, this study demonstrates that the optimized multichannel ANAs have great potential for clinical application and offer new insight into the further improvement of ANAs.

NLRP3 inflammasome activation in response to metals

“…In addition, Zn can inhibit high glucose-induced NLRP3 inflammasome activation in peritoneal mesothelial cells by attenuating ROS production (38). Zn also played a neuroprotective role by suppressing NLRP3 inflammasome activation through autophagy and ubiquitination in an experimental spinal cord injury model (39,83). Another study also showed that Zn suppressed NLRP3 activation by inducing microglia autophagy and played a neuroprotective role in spinal cord injury (40).…”

Biomedical Application of Decellularized Scaffolds

“…And with the advancement of medical technology and knowledge, the success rate of peripheral nerve therapy has significantly increased . However, due to the limitation of nerve regeneration capacity, there are still huge clinical challenges in improving peripheral nerve repair and regeneration . In recent years, researchers have been trying to find a substitute for neural tissue to replace autologous nerve transplantation.…”

“…251 However, due to the limitation of nerve regeneration capacity, there are still huge clinical challenges in improving peripheral nerve repair and regeneration. 252 In recent years, researchers have been trying to find a substitute for neural tissue to replace autologous nerve transplantation. Tissue engineering has become an important research topic in the field of neural regeneration.…”

Advanced technologies for biomedical applications by emerging researchers in Asia‐Pacific

“…Applying these ANAs in peripheral nerve regeneration holds promise for clinical use. 34 Yu et al engineered a structurally organized bladder construct by integrating buccal mucosa graft with vascularized smooth muscle tissue, which facilitated the repair of functional bladder defects. 35…”

“…Yu et al prepared innovative acellular nerve allografts (ANAs), which could retain a higher concentration of extracellular matrix bioactive molecules and regenerative factors while efficiently eliminating cellular antigens. Applying these ANAs in peripheral nerve regeneration holds promise for clinical use 34 . Yu et al engineered a structurally organized bladder construct by integrating buccal mucosa graft with vascularized smooth muscle tissue, which facilitated the repair of functional bladder defects 35 …”