Extracellular Matrix Mimicking Biomaterials as a Paradigm Shift in Nerve Repair and Regeneration

ABSTRACT Extracellular matrix (ECM)‐mimicking biomaterials have revolutionized nerve repair by providing structural, biochemical, and mechanical support to injured neural tissues. These biomaterials emulate the natural ECM, fostering cell adhesion, proliferation, and differentiation, which are critical for axonal regeneration. Advances in biomaterial engineering have enabled the development of synthetic and natural scaffolds designed to replicate the intricate microarchitecture of the ECM. Advances in biomaterial engineering have enabled the development of both synthetic and natural scaffolds, such as collagen‐based scaffolds, polyethylene glycol (PEG) hydrogels, and decellularized ECM matrices, designed to replicate the intricate microarchitecture of the ECM. Key features such as biocompatibility, biodegradability, and bioactivity are tailored to meet the dynamic needs of nerve repair. This article reviews the latest progress in ECM‐mimicking biomaterials, focusing on their composition, fabrication techniques, and applications in peripheral and central nervous system repair. Innovations such as 3D bioprinting, nanotechnology, and functionalized hydrogels are explored for their ability to enhance scaffold performance. Additionally, the incorporation of bioactive molecules like growth factors, cytokines, and neurotrophic factors is discussed for their role in promoting neural tissue regeneration. The synergy between ECM‐mimicking biomaterials and stem cell‐based therapies is highlighted as a promising avenue for achieving functional nerve recovery. Despite significant advancements, challenges such as immune responses, scalability, and clinical translation remain barriers to widespread adoption. Addressing these limitations requires interdisciplinary collaboration to optimize biomaterial design and standardize preclinical and clinical evaluations. This review underscores the transformative potential of ECM‐mimicking biomaterials in nerve repair and their role in shaping future regenerative medicine.