Hydrogels for Peripheral Nerve Repair: Emerging Materials and Therapeutic Applications

Peripheral nerve injuries pose a significant clinical challenge due to the complex biological processes involved in nerve repair and their limited regenerative capacity. Despite advances in surgical techniques, conventional treatments, such as nerve autografts, are faced with limitations like donor site morbidity and inconsistent functional outcomes. As such, there is a growing interest in new, novel, and innovative strategies to enhance nerve regeneration. Tissue engineering/regenerative medicine and its use of biomaterials is an emerging example of an innovative strategy. Within the realm of tissue engineering, functionalized hydrogels have gained considerable attention due to their ability to mimic the extracellular matrix, support cell growth and differentiation, and even deliver bioactive molecules that can promote nerve repair. These hydrogels can be engineered to incorporate growth factors, bioactive peptides, and stem cells, creating a conducive microenvironment for cellular growth and axonal regeneration. Recent advancements in materials as well as cell biology have led to the development of sophisticated hydrogel systems, that not only provide structural support, but also actively modulate inflammation, promote cell recruitment, and stimulate neurogenesis. This review explores the potential of functionalized hydrogels for peripheral nerve repair, highlighting their composition, biofunctionalization, and mechanisms of action. A comprehensive analysis of preclinical studies provides insights into the efficacy of these hydrogels in promoting axonal growth, neuronal survival, nerve regeneration, and, ultimately, functional recovery. Thus, this review aims to illuminate the promise of functionalized hydrogels as a transformative tool in the field of peripheral nerve regeneration, bridging the gap between biological complexity and clinical feasibility.