Drug-delivery strategies using biomaterials in the field of nerve regeneration

Neural injuries can cause considerable functional impairments, and both central and peripheral nervous systems have limited regenerative capacity. The existing conventional pharmacological treatments in clinical practice show poor targeting, rapid drug clearance from the circulatory system, and low therapeutic efficiency. Therefore, in this review, we have first described the mechanisms underlying nerve regeneration, characterized the biomaterials used for drug delivery to facilitate nerve regeneration, and highlighted the functionalization strategies used for such drug-delivery systems. These systems mainly use natural and synthetic polymers, inorganic materials, and hybrid systems with advanced drug-delivery abilities, including nanoparticles, hydrogels, and scaffold-based systems. Then, we focused on comparing the types of drug-delivery systems for neural regeneration as well as the mechanisms and challenges associated with targeted delivery of drugs to facilitate neural regeneration. Finally, we have summarized the clinical application research and limitations of targeted delivery of these drugs. These biomaterials and drug-delivery systems can provide mechanical support, sustained release of bioactive molecules, and enhanced intercellular contact, ultimately reducing cell apoptosis and enhancing functional recovery. Nevertheless, immune reactions, degradation regulation, and clinical translations remain major unresolved challenges. Future studies should focus on optimizing biomaterial properties, refining delivery precision, and overcoming translational barriers to advance these technologies toward clinical applications.