Advances in smart hydrogels for nerve repair: A review focusing on criteria and applications
Yasaman Mozhdehbakhsh Mofrad, Sasan Asiaei, Hossein Shaygani, Fatemeh Cheraghi, Soumayeh Amirsaadat, Mohammadreza Soltani, Farina Dehghan Nezhad Derarandash, Maedeh Shams, S Zare, Amir Shamloo
Abstract
Smart hydrogels are emerging as highly promising biomaterials for nerve tissue engineering due to their ability to mimic the extracellular matrix (ECM) and deliver therapeutic agents in a controlled manner. This review specifically highlights key selection criteria for smart hydrogels, including mechanical properties, degradation rate, electrical conductivity, biocompatibility, and responsiveness to biochemical or physical stimuli. Evidence from recent studies shows that conductive and bioactive hydrogels enhance neuron differentiation and axon guidance, while injectable formulations facilitate minimally invasive central nervous system (CNS) and peripheral nervous system (PNS) repair. Current challenges include ensuring consistent performance, regulatory approval, and translation from small to large-animal models. Finally, the review identifies future research directions, such as developing adaptive hydrogels that respond to local inflammation, optimizing drug and cell delivery, and advancing personalized hydrogel therapies based on patient-specific genetics, aiming to guide the field toward clinically translatable neural regeneration solutions.