Enhancing peripheral nerve regeneration through <scp>NaOH</scp> ‐based decellularization of human nerve tissue

Peripheral nerves are vulnerable to trauma, pressure, and surgical injuries, complicating the regeneration process. While the autograft remains the gold standard for recovery, limitations such as tissue availability and donor site morbidities have led to the exploration of the allografts. However, conventional detergent-based decellularization methods in preparing allografts often cause residual toxicity and damage to the extracellular matrix (ECM). To address such challenges, we propose a sodium hydroxide (NaOH)-based decellularization technique that minimizes harmful residues. Our findings demonstrate that this method effectively removes inflammatory materials while preserving the ECM components and structures, and significantly reduces lipid and detergent residues. In vitro studies confirmed that the human nerves processed with the NaOH-based decellularization technique show low cytotoxicity and support elevated cell viability and proliferation. We further compared the performance of NaOH-based decellularized human nerves with that of autografts through an in vivo rabbit sciatic nerve defect model. NaOH-based decellularized nerves showed functional recovery comparable to autografts. Our findings demonstrate structural regeneration through neurofilament and laminin expression, indicating recovery levels similar to those of autografts. This study highlights that decellularized human nerve grafts through the NaOH-based protocol can promote nerve regeneration comparable to autografts, which can offer a safe and effective option for the treatment and reconstruction of peripheral nerve defects.