Functional nanomaterials in peripheral nerve regeneration: Scaffold design, chemical principles and microenvironmental remodeling

Neuronal microenvironment imbalance is associated with successive and irreversible pathophysiological changes and insufficient functional restoration after peripheral nerve injury. Conventional neural-supporting scaffolds result in unsatisfactory curative effects due to lack of biomimetic nanotechnology designs and biochemical or physicochemical modifications. Consequently, they fail in rational and facile remodeling of the imbalanced growth microenvironment, and cannot recover neural structure and function. In recent years, with the increasing knowledge in neuronal injury-associated microenvironment, a number of novel strategies are applied in enhancing the biochemical and physicochemical natures of biomimetic nanomaterial-based scaffolds for nerve tissue engineering. These nanoscale scaffolds can trigger growth factor secretion and aggregation through surface modification, regulate ATP synthesis and hydrolysis, switch between oxidation and reduction states, and activate ion channels and stimulate electrical signals under certain biophysical cues. Consequently, they can determine neuronal cell fate by modulating their viability, development and cell cycles during the regeneration process. In this review, we systematically summarize the studies on the biomimetic scaffold design of functional nanomaterials, their basic topological, biochemical and physical properties, and nanotechnology-based restoration of a balanced nutritional microenvironment regarding four key neural regeneration factors, including immune response, intraneural vascularization, bioenergetic metabolism and bioelectrical conduction in order to provide ideas and inspiration for the nanomedicine-based neuronal regeneration therapy.