Abstract: Traditional nerve repair methods, such as autologous nerve grafting and allogeneic nerve grafting, face issues such as donor shortage, functional loss, and immune rejection. Decellularized extracellular matrix-based grafts have emerged as highly promising alternatives, capable of uniquely recreating the natural neural microenvironment, promoting host cell remodeling, and ultimately enhancing functional neural regeneration. This review comprehensively analyzes the key mechanisms of peripheral nerve injury and regeneration, focusing on contemporary therapeutic strategies for key aspects such as axonal apoptosis inhibition, enhanced intrinsic regenerative capacity, construction of regenerative microenvironment, and prevention of target organ atrophy. Findings from this review has shown that decellularized extracellular matrix grafts can promote the migration, proliferation, and differentiation of nerve cells by providing physical support, chemical signals, and mechanical stability. Decellularized extracellular matrix grafts are mainly used as nerve conduits, scaffolds, hydrogels, and 3D printing inks. Decellularized extracellular matrix grafts have demonstrated significant advantages in promoting nerve regeneration by regulating the proliferation and differentiation of Schwann cells, improving the neural microenvironment, reducing inflammatory responses, and promoting angiogenesis. Additionally, decellularized extracellular matrix grafts can serve as drug carriers, enabling the controlled release of growth factors, which further enhances nerve regeneration. However, these grafts also have some limitations, including the presence of immunogenic residues, inadequate mechanical properties, inter-batch variability, and uncontrollable degradation rates. Future research should focus on optimizing the decellularization process, enhancing the mechanical properties of decellularized extracellular matrix grafts, reducing immunogenicity, improving biocompatibility and safety, and developing new composite materials. Furthermore, exploring their application potential in complex nerve injuries, such as diabetic neuropathy, is crucial to meet the needs of peripheral nerve regeneration and repair.

Key words: biological cues, biological scaffold, decellularization, decellularized extracellular matrix graft, decellularized tissue, extracellular matrix, nerve repair and regeneration, peripheral nerve injury, regenerative medicine, tissue engineering