This award by the Biomaterials program in the Division of Materials Research to University of Alabama at Birmingham is to develop biologically-active biomaterials for potential treatment of an autoimmune disease, such as Type 1 diabetes (T1D). Restoring immune tolerance, i.e., the inability of the immune system to respond to specific autoantigens such as insulin is a major challenge in T1D. To address this challenge, this project will develop novel immunoprotective polymeric nano- and micro-particles with encased insulin to dampen aberrant Type 1 diabetes autoimmune responses. This research will impact the design and application of a new type of polymer material with autoimmune modulating activity and will provide a fundamental understanding of the physical and chemical properties of these materials at biological interfaces. The design of this material will open new prospects in various bio-related areas such as bioengineering and tissue engineering and autoimmune therapies. The educational objective of this project is to develop a discovery-driven multidisciplinary biomaterials/polymer sciences program at University of Alabama at Birmingham in promoting diversity from the high school through graduate-level. These students, including underrepresented minorities, will be trained in modern aspects of biopolymer sciences including state-of-the-art synthetic and analytical methods, and they will take part in intensive multidisciplinary collaborations between the Departments of Chemistry and Microbiology.
The goal of this proposal is to develop a new type of immunomodulatory particulate material with encased autoantigens (insulin) for dampening autoimmune responses in Type 1 diabetes (T1D), and to gain a fundamental understanding of the mechanism of immune modulating activity. These hollow particles will be designed through hydrogen-bonded assemblies of polyphenolic tannic acid (TA) with neutral polymers to produce micro- and nano-capsules for delivery of insulin to immune cells and restore their immune tolerance. The objectives of the proposed study are as follows: 1) synthesis TA-based microcapsules with novel temperature-sensitive diblock copolymers, and explore their immune cell uptake properties; 2) explore the loading of insulin into capsules with tunable thermal, antioxidant and anti-inflammatory properties; 3) investigate immunomodulation of antigen-presenting cells with TA-based capsules with dampening autoimmune responses in an autoantigen-specific manner; and 4) study the interaction of these materials with antigen-presenting cells in vitro. Correlations between material physical/chemical properties and function of immune cells is pivotal for transformative knowledge in developing immunomodulatory materials for treating a broad spectrum of autoimmune diseases. Access to state-of-the-art techniques with unique capabilities of in situ nano-scaled measurements, advanced imaging, and immunology facilities will ensure the successful completion of the project. Recruitment and/or mentoring of students at different levels - High school, undergraduate, and graduate including underrepresented minorities - and training them in modern aspects of biopolymer sciences including state-of-the-art synthetic and analytical methods are parts of this award.
