Repairing spinal cord injuries: the most promising current 1 biomaterials 2 for scaffolding and drug delivery, and the need for upgrade

Abstract: Spinal Cord Injury (SCI) results in severe sensory and motor deficits, with dramatic impact in lifespan and healthspan, due to the limited regenerative capacity of the central nervous system. Following the initial injury, glial scarring and extracellular matrix barriers prevent axonal regeneration, while secondary damage exacerbates inflammation and tissue loss. The gold standard treatment in the last decades is acute surgery and systemic drug administration. New technologies have been developed, such as stem cell therapies, or the combinatory use of biomaterials, nonetheless still offering limited recovery. Successful therapies must act directly on neurons, activating regenerative pathways, while simultaneously promoting a pro-regenerative environment. However, polymeric materials have in recent years shown a regenerative potential through a series of different processes, from promoting neural regeneration by supporting tissue repair and reducing inflammation, to local drug delivery mechanisms. In this work, we systematize the state-of-the-art, exploring recent advancements in polymer-based therapies for SCI, discussing their characteristics, limitations, and promising future applications.