Immunomodulatory ultrathin coatings for pancreatic islet transplantation

用于胰岛移植的免疫调节超薄涂层

• 批准号: 1306110
• 负责人: Eugenia Kharlampieva
• 金额: $ 50万
• 依托单位: University of Alabama at Birmingham
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1306110&HistoricalAwards=false
• 关键词: Immunomodulatory; ultrathin; coatings; pancreatic; islet

ID: MPS/DMR/BMAT(7623) 1306110 PI: Kharlampieva, Eugenia ORG: University of Alabama-BirminghamTitle: Immunomodulatory Ultrathin Multilayer Coatings for Pancreatic Islet TransplantationTechnical: Although transplantation of pancreatic islet cells has emerged as a promising treatment for Type 1 diabetes, its clinical application remains limited due to adverse effects of immunosuppression and declining allograft function. To overcome these hurdles, a preclinical approach to protect isolated islets and to modulate autoimmune responses in Type 1 diabetes is proposed. The goal of this proposal is to develop novel cytoprotective coatings with controlled immunomodulatory and inflammatory responses, and to gain insight into the fundamental mechanism of the coating activity to preserve islet viability and function. These coatings will be designed through layer-by-layer hydrogen-bonded assembly of cytocompatible macromolecules with antioxidant and anti-inflammatory characteristics. The objectives of the proposed study are as follows: (1) Synthesize ultrathin coating materials with a layer-by-layer hydrogen-bonded assembly approach. A series of novel functional copolymers with antioxidant metalloporphyrin modality will be synthesized and self-assembled through hydrogen-bonding interactions. (2) Define the immunomodulatory effects of 'islet-free' coatings in vitro. A novel polymer coating with advanced antioxidant and anti-inflammatory activity will be obtained. The coatings are adaptable and can be further modified to facilitate non-invasive imaging. (3) Evaluate the immunomodulatory effects of 'on-islet' coating in response to immune challenges in vitro. These efforts will establish fundamental correlations with biomaterial properties and islet function, and provide transformative knowledge for modification of other living cell types in a rapid and efficient manner. Non-Technical: The proposed research presents new opportunities for the development of novel cytoprotective materials to be used for basic research applications as well as a cell-based transplantation therapy for diabetic recipients. Our proposal is particularly timely since current islet encapsulation systems are challenging for transplantations due to high cytotoxicity and the requirement for large injection volumes. The design of novel immunoprotective materials will open new prospects for developing biomaterials with unique characteristics having applications in various bio-related areas such as bioengineering and tissue engineering. The educational objective of this project is to develop a discovery-driven, multidisciplinary biomaterials/polymer sciences program at UAB to promote diversity from the high school through graduate-level. The PI is currently developing a polymer science program at UAB with a specific focus on biomaterials at the B.S. and Ph.D. levels. High school, undergraduate, and graduate students, including underrepresented minorities, will be trained in modern aspects of biopolymer science including state-of-the-art synthetic and analytical methods, and will take part in intensive multidisciplinary collaborations throughout and beyond UAB. The proposed activities will develop interdisciplinary collaborative research between the Departments of Chemistry, Surgery, and Microbiology. These collaborative efforts will stimulate awareness of the needs of the UAB biomedical research community for specialized polymer-based biomaterials as novel platforms for cell transplantation therapy. The results will be disseminated through publications in peer-reviewed journals and presentations at national and international scientific conferences.

ID：MPS/DMR/BMAT（7623）1306110 PI：Kharlampieva，Eugenia ORG：题目：胰岛移植免疫调节超薄多层膜技术：尽管胰岛细胞移植已成为1型糖尿病的一种有前景的治疗方法，但由于免疫抑制和同种异体移植功能下降的不良反应，其临床应用仍然有限。 为了克服这些障碍，提出了一种保护分离的胰岛和调节1型糖尿病自身免疫反应的临床前方法。 该提案的目标是开发具有受控免疫调节和炎症反应的新型细胞保护涂层，并深入了解涂层活性的基本机制，以保持胰岛活力和功能。 这些涂层将通过具有抗氧化和抗炎特性的细胞相容性大分子的逐层氢键组装来设计。 本论文的主要研究内容如下：（1）采用逐层氢键组装的方法合成纳米涂层材料。 本论文将合成一系列新型的具有抗氧化功能的金属卟啉共聚物，并通过氢键作用进行自组装。 (2)确定“无胰岛”涂层的体外免疫调节作用。 将获得具有高级抗氧化剂和抗炎活性的新型聚合物涂层。 涂层是可适应的，并且可以进一步修改以促进非侵入性成像。 (3)评价“胰岛上”涂层对体外免疫激发的免疫调节作用。 这些努力将建立与生物材料特性和胰岛功能的基本相关性，并以快速有效的方式为其他活细胞类型的修饰提供变革性知识。 非技术：拟议的研究为开发用于基础研究应用的新型细胞保护材料以及糖尿病受体的细胞移植治疗提供了新的机会。 我们的建议是特别及时的，因为目前的胰岛封装系统是具有挑战性的移植，由于高细胞毒性和大注射体积的要求。 新型免疫保护材料的设计将为开发具有独特特性的生物材料开辟新的前景，这些生物材料在生物工程和组织工程等各种生物相关领域具有应用。 该项目的教育目标是在UAB开发一个以发现为导向的多学科生物材料/聚合物科学项目，以促进从高中到研究生阶段的多样性。 PI目前正在UAB开发一个聚合物科学项目，重点关注B.S.的生物材料。和博士程度. 高中，本科和研究生，包括代表性不足的少数民族，将接受生物聚合物科学的现代方面的培训，包括最先进的合成和分析方法，并将参加UAB内外的密集多学科合作。 拟议的活动将发展化学，外科和微生物学部门之间的跨学科合作研究。这些合作努力将激发UAB生物医学研究界对专业聚合物基生物材料的需求的认识，作为细胞移植治疗的新平台。研究结果将通过在同行评审期刊上发表文章以及在国家和国际科学会议上发表演讲的方式传播。