Say Yes to NO: The Next Generation Scaffolds with Localized and Sustained Nitric Oxide (NO) Delivery for Central Nervous System Regeneration

Central nervous system injuries (CNSIs), such as traumatic brain injury and spinal cord injury, are highly complex conditions that often cause critical impairment in motion, sensation and cognition, which severely affects patients' quality of life. The estimated annual incidence for TBI and SCI is 9390 and 246 per million people worldwide, creating a tremendous socioeconomic burden. To address this issue, researchers have developed many solutions such as nerve grafts, cell transplantation, and engineered scaffolds, among which engineered scaffolds have received much attention owing to their ability to provide structural support and topographical cues to direct cell fates and tissue regrowth. These scaffolds have been used as carriers to deliver various growth factors to enhance neural regeneration. However, the efficacy of such systems remains sub-optimal. This is because these scaffolds can only deliver therapeutics over a short period of time (i.e., days to weeks) owing to the finite loading capacities and face the issue of uncontrolled release of the
cargos due to the complexity of the milieu of the injured sites. In an attempt to overcome these challenges, I will establish the first scaffold that allows for localized and controlled NO release over an extended timeframe (i.e., months) that is sufficient to aid central nervous system regeneration. NO has been implicated to regulate the proliferation, survival and differentiation of neurons. The sustained NO release will be realized by encapsulating enzyme mimetic partcles into the scaffolds, serving as biological machinery to catalyze endogenous NO prodrugs to release NO.