Novel biomaterials for IBD treatment

摘要 超过300万美国成年人被诊断为炎症性肠病(IBD)。目前的IBD治疗方法，如 作为免疫抑制剂和生物制品，治疗IBD的症状；然而，它们通常不能解决 潜在原因，包括肠道屏障功能缺陷，促炎细胞因子水平异常 和免疫细胞，以及失调的肠道共生微生物。因此，迫切需要新的 IBD的治疗方法。此外，肠道微生物组正在成为药物开发的下一个前沿。 然而，如何有效地调节肠道微生物群以达到治疗目的仍不清楚。我们的长- 学期研究目标是开发新的肠道靶向策略，以调节先天性免疫和肠道微生物群。 我们在这一应用程序中的目标是生成关于生物材料参数的新的基本知识 有效靶向炎症的结肠，随后恢复肠道屏障功能和健康的肠道 IBD中的微生物区系。为了这个目标，我们开发了一种新的生物材料系统，可以针对发炎的结肠 并在发炎的结肠上皮中启动愈合反应。在这里，使用我们的生物材料系统作为起点 平台，我们寻求发现新的材料标准，以设计最佳结肠靶向(AIM)的生物材料 1)、调节先天免疫(目标2)和调节肠道微生物区系(目标3)。 总体而言，我们的提案的成功完成将使结肠靶向给药系统发挥作用 对IBD有很强的疗效。

Abstract Over 3 million U.S. adults are diagnosed with inflammatory bowel disease (IBD). The current IBD therapies, such as immunosuppressants and biologics, treat the symptoms of IBD; however, they generally do not address the underlying causes, including defective intestinal barrier functions, abnormal levels of pro-inflammatory cytokines and immune cells, and dysregulated gut commensal microbes. Thus, there exists a critical need for new approaches for treatment of IBD. Moreover, gut microbiome is emerging as the next frontier in drug development. However, it remains unknown how to effectively regulate the gut microbiome for therapeutic purposes. Our long- term research goal is to develop new gut-targeted strategies for modulating innate immunity and gut microbiome. Our objectives in this application is to generate new fundamental knowledge on biomaterial parameters for efficient targeting of inflamed colon and subsequent restoration of intestinal barrier functions and healthy gut microbiota in IBD. Toward this goal, we have developed a new biomaterial system that can target inflamed colon and initiate healing responses in inflamed colonic epithelium. Here, using our biomaterial system as a starting platform, we seek to uncover new materials criteria for designing biomaterials for optimal colon targeting (Aim 1), regulation of innate immunity (Aim 2), and modulation of the gut microbiota (Aim 3) in the context of IBD. Overall, successful completion of our proposal will enable colon-targeted drug delivery systems that will exert potent efficacy against IBD.