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

对“否”说“是”：具有局部和持续一氧化氮 (NO) 输送的下一代支架，用于中枢神经系统再生

• 批准号: EP/X027198/2
• 负责人: Molly Stevens
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX027198%2F2
• 关键词: Say; Yes; NO; Next; Generation

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.

中枢神经系统损伤（CNSI），如创伤性脑损伤和脊髓损伤，是高度复杂的疾病，通常会导致严重的运动，感觉和认知障碍，严重影响患者的生活质量。TBI和SCI的估计年发病率分别为9390和246/百万人，造成了巨大的社会经济负担。为了解决这个问题，研究人员已经开发了许多解决方案，如神经移植，细胞移植和工程支架，其中工程支架由于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受到广泛关注。这些支架已被用作载体，以提供各种生长因子，以促进神经再生。然而，这种系统的功效仍然是次优的。这是因为这些支架只能在短时间内递送治疗剂（即，由于装载能力有限，需要几天到几周的时间，而且由于受伤地点环境的复杂性，面临着货物不受控制地释放的问题。为了克服这些挑战，我将建立第一个允许在延长的时间范围内局部和受控NO释放的支架（即，这足以帮助中枢神经系统再生。NO参与调节神经元的增殖、存活和分化。通过将酶模拟颗粒包裹在支架中，作为生物机械催化内源性NO前药释放NO，实现NO的持续释放。