Novel biomaterials for IBD treatment

用于治疗 IBD 的新型生物材料

• 批准号: 10611921
• 负责人: Nobuhiko Kamada
• 金额: $ 63.44万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10611921
• 关键词: Acute; Adult; Affect; American; Benchmarking; Bilirubin; Binding; Biocompatible Materials; Biological Products; CD44 gene; Cells; Colitis; Colon; Colonic inflammation; Cytoprotection; Diagnosis; Disease; Drug Delivery Systems; Drug Targeting; Epithelium; Germ-Free; Goals; Human; Hyaluronic Acid; Immune; Immunosuppressive Agents; Infection; Inflammatory; Inflammatory Bowel Diseases; Interleukin-1 beta; Interleukin-6; Intestines; Knowledge; Macrophage; Mononuclear; Mus; Natural Immunity; Oral Administration; Phagocytes; Pharmaceutical Preparations; Property; Regulation; Research; Role; System; TNF gene; Therapeutic; Translations; Transplantation; Treatment Efficacy; commensal bacteria; commensal microbes; cytokine; design; drug development; early phase clinical trial; fecal transplantation; frontier; gastrointestinal epithelium; gut inflammation; gut microbiome; gut microbiota; healing; human microbiota; humanized mouse; immunosuppressed; intestinal barrier; microbiome therapeutics; microbiota; monocular; monocyte; mouse model; nanoformulation; nanoparticle; novel; novel therapeutic intervention; response; restoration; self assembly; symptom treatment

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.

摘要 超过300万美国成年人被诊断患有炎症性肠病（IBD）。目前的IBD疗法，如 作为免疫抑制剂和生物制剂，治疗IBD的症状;然而，它们通常不能解决IBD的症状。 根本原因，包括肠屏障功能缺陷，促炎细胞因子水平异常 免疫细胞和失调的肠道微生物。因此，迫切需要新的 治疗IBD的方法。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组以达到治疗目的仍然是未知的。我们长久以来- 长期研究目标是开发新的肠道靶向策略，用于调节先天免疫和肠道微生物组。 我们在此应用中的目标是产生关于生物材料参数的新的基础知识， 有效靶向发炎的结肠并随后恢复肠屏障功能和健康的肠道 IBD中的微生物群。为了实现这一目标，我们开发了一种可以针对炎症结肠的新生物材料系统 并在发炎的结肠上皮中引发愈合反应。在这里，使用我们的生物材料系统作为一个开始， 平台，我们寻求发现新的材料标准，设计生物材料的最佳结肠靶向（目的 1），先天免疫的调节（目的2），和肠道微生物群的调节（目的3）在IBD的背景下。 总的来说，成功完成我们的提案将使结肠靶向药物输送系统，将发挥 对IBD的有效治疗。

项目成果

A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo.

• DOI: 10.1016/j.xcrm.2022.100774
• 发表时间: 2022-10-18
• 期刊: CELL REPORTS MEDICINE
• 影响因子: 14.3
• 作者: Chan, Jasper Fuk-Woo;Oh, Yoo Jin;Yuan, Shuofeng;Chu, Hin;Yeung, Man-Lung;Canena, Daniel;Chan, Chris Chung-Sing;Poon, Vincent Kwok-Man;Chan, Chris Chun-Yiu;Zhang, Anna Jinxia;Cai, Jian-Piao;Ye, Zi-Wei;Wen, Lei;Yuen, Terrence Tsz-Tai;Chik, Kenn Ka-Heng;Shuai, Huiping;Wang, Yixin;Hou, Yuxin;Luo, Cuiting;Chan, Wan-Mui;Qin, Zhenzhi;Sit, Ko-Yung;Au, Wing-Kuk;Legendre, Maureen;Zhu, Rong;Hain, Lisa;Seferovic, Hannah;Tampe, Robert;To, Kelvin Kai-Wang;Chan, Kwok-Hung;Thomas, Dafydd Gareth;Klausberger, Miriam;Xu, Cheng;Moon, James J.;Stadlmann, Johannes;Penninger, Josef M.;Oostenbrink, Chris;Hinterdorfer, Peter;Yuen, Kwok-Yung;Markovitz, David M.
• 通讯作者: Markovitz, David M.