A Roadmap of Peptide-Based Materials in Neural Regeneration

Injuries to the nervous system lead to irreversible damage and limited functional recovery. The peripheral nervous system (PNS) can self-regenerate to some extent for short nerve gaps. In contrast, the central nervous system (CNS) has an intrinsic limitation to self-repair owing to its convoluted neural microenvironment and inhibitory response. The primary phase of CNS injury, happening within 48 h, results from external impacts like mechanical stress. Afterward, the secondary phase of the injury occurs, originating from neuronal excitotoxicity, mitochondrial dysfunction, and neuroinflammation. No golden standard to treat injured neurons exists, and conventional medicine serves only as a protective approach to alleviating the symptoms of chronic injury. Synthetic peptides provide a promising approach for neural repair, either as soluble drugs or by using their intrinsic self-assembly propensity to serve as an extracellular matrix (ECM) mimic for cell adhesion and to incorporate bioactive epitopes. In this review, an overview of nerve injury models, common in vitro models, and peptide-based therapeutics such as ECM mimics is provided. Due to the complexity of treating neuronal injuries, a multidisciplinary collaboration between biologists, physicians, and material scientists is paramount. Together, scientists with complementary expertise will be required to formulate future therapeutic approaches for clinical use.