Technical: 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.
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.
