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

中枢神经系统损伤(CNSI)，如创伤性脑损伤和脊髓损伤，是一种高度复杂的疾病，往往会导致严重的运动、感觉和认知障碍，严重影响患者的生活质量。据估计，颅脑损伤和脊髓损伤的年发病率在全球每百万人中分别为9390和246人，造成巨大的社会经济负担。为了解决这一问题，研究人员开发了许多解决方案，如神经移植、细胞移植和工程支架，其中工程支架因其能够提供结构支撑和地形线索来指导细胞命运和组织再生而备受关注。这些支架已被用作载体来运送各种生长因子，以促进神经再生。然而，这类系统的效果仍然不是最好的。这是因为，由于承载能力有限，这些支架只能在短时间内(即几天到几周)提供治疗药物，并且由于受伤部位环境的复杂性，面临着心脏不受控制的释放问题。为了克服这些挑战，我将建立第一个支架，允许在足以帮助中枢神经系统再生的较长时间(即几个月)内局部和受控地释放NO。NO参与调节神经元的增殖、存活和分化。NO的持续释放是通过将模拟酶的部分包裹到支架中，作为生物机械催化内源性NO前体药物释放NO来实现的。

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 thecargos 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.