Immunomodulatory ultrathin coatings for pancreatic islet transplantation Eugenia Kharlampieva, University of Alabama at Birmingham, DMR Transplantation of pancreatic islets (cell clusters) emerged as a promising treatment for Type 1 Diabetes, though its clinical application is constrained due to limited availability of the islets, adverse effects of immunosuppression, and declining allograft function. Current islet modification strategies are challenging for transplantation due to interference with islet function, limited nutrient transport, and cytotoxicity. The Kharlampieva Group is developing novel cytoprotective coatings with controlled immunomodulatory and inflammatory responses, and exploring the fundamental mechanism of the coating immunomodulatory activity. The coating is designed through a layer-by-layer (LbL) hydrogen-bonded assembly of natural antioxidant, tannic acid (TA) and synthetic polymer, polyvinylpyrrolidone (PVPON) (Fig. 1) and allows for enhanced viability and function of the encapsulated cell islets. This year we have developed synthesis of well-defined homopolymers of PVPON and its hydrophobic homologue PVCL with controlled molecular weights and size distributions using MADIX/RAFT polymerization (Fig. 2). The (TA/PVPON) coating was found to be stable at pH=7.4 without any disintegration for at least a month which is highly relevant for our studies on encapsulated islets in vitro. Additionally, we found that TA itself does not leach from TA/PVPON coating, which is crucial for long-term cell encapsulation for islet transplantation. Fig. 1. Pancreatic islets (left top). Chemical structures of TA and PVPON (left bottom). Islet encapsulation in a (PVPON/TA)n multilayer at pH=7.4 (right). Fig. 2. Synthesis of PVCL and PVPON homopolymers and double hydrophilic PVCL-b-PVPON and PVPON-b-PVCL diblock copolymers using RAFT polymerization.

o Overall, one postdoctoral associate and 4 graduate students, Jun Chen, Xing Liang, Bing Xue, and Fei Liu participated in the NSF project during Spring 2013-Spring o Xing Liang was recognized with the UAB College of Arts and Sciences Outstanding Graduate Student Award and received the Department of Chemistry Travel Award, which provided him an opportunity to attend the 247th Spring 2014 ACS meeting in Dallas, TX. o Since beginning the NSF project in 2013, five undergraduate students (through support from the NSF REU and UAB Research for undergraduates programs) including two female and one male students from underrepresented minority groups participated in the project. They received training in polymer chemistry and biomaterials-related research. o The project has enabled the collaboration with the Department of Biochemistry and Molecular Biology at the Southern Research Institute (SRI, Birmingham, AL). This collaboration has been providing the graduate students the opportunities to work closely with researchers from SRI and to become exposed to the modern aspects of polymer science and biochemistry. Fig. 2. An NSF REU student, Claudia Martinez-Lopez participated in the project during Summer She presented her research at the UAB 2013 research Expo. Fig. 3. Simone Ridgeway, a graduate student in UAB Biotechnology program worked on Type I diabetes-related research in the Kharlampieva Group during Summer Her work was supported by American Heart Association Fellowship. Immunomodulatory ultrathin coatings for pancreatic islet transplantation Eugenia Kharlampieva, University of Alabama at Birmingham, DMR Fig. 1. Undergraduate students, Allison Goins, Christopher Cox, and Claudia Martinez-Lopez participated in the project during Summer-Fall 2013 and have earned their co-authorship in the resulted publications (three published).