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Academic Inventions through Multidisciplinary Collaborations between Weill Cornell Medical College and Ithaca Campuses Bo Liu Division of Vascular Surgery Translate inventions in material science to novel treatments for vascular diseases. Vascular Surgeons Experimental hypotheses Material Scientists Vascular Biologists Project I: DNA Carriers Problem: Lack of safe and efficient DNA/RNA carriers for molecular therapy. O * O x O H N H C C O O O y C NH Hypothesis: Newly invented PEA polymers are capable of binding DNA and delivering it to vascular cells and tissues. H2 N H C H N * NH NH2 H2 N NH2 PEA polymer Cornell University Seed Grant (Liu & Chu) 11/1/06-10/31/07 Novel biodegradable biomaterials as non-viral gene transfer systems. Cytotoxicity healthy SMC 15 μg PEA 1,500 μg PEA Control – no transfection unhealthy 15 μg PEI 15 μg Superfect® Higher %, more cell friendly Cytotoxicity: Cell Viability Transfection Efficiency in SMC RLU/mg Firefly 4.5E+05 4.0E+05 3.5E+05 3.0E+05 2.5E+05 2.0E+05 1.5E+05 1.0E+05 5.0E+04 0.0E+00 SF 2-A-6E-Cl100 2-A-6E-Cl200 Commercial reagent 2-A-6E-Cl500 2-A-6E-Cl-1K 2-A-6E-Cl-2K Chu’s PEA samples SMC Transfection by DNA Encoded with Green Fluorescence Protein Outcome: grant proposals NIH R21/R33 submitted on 9/16/07 Novel biodegradable polymers as non-viral gene transfer systems. Liu, Kent, Rafii, and Chu The Uehara Memorial Foundation (Japan) Research Fellowship----- 1/01/08 to 12/31/09 Yamanochi Outcome: publication Transfection of Vascular Smooth Muscle Cells with Novel Biodegradable Arginine Based Poly(ester-amide)s Dai Yamanouchi, M.D., Ph.D.,1, Jun Wu,2, Andrew Lazar,1, K Craig Kent, MD.,1, Chih-Chang Chu, Ph.D.,2, Bo Liu, Ph.D.1. 1. Weill Medical College; 2. Cornell University Submitted to Molecular Therapy Project II: Tissue engineering of blood vessels Problem: Synthetic arterial grafts fail due to restenosis. Approach: Using biodegradable materials as scaffold to generate blood vessels ex vivo or in vitro. Morgan Seed Grant (Chu, Peinhart-King, Liu, and Kent) 7/1/07-12/31/08 Novel biodegradable scaffolds for tissue engineering of blood vessels. Chu: Human Ecology Synthesis of PEA-based biodegradable and biofunctional elastomeric scaffolds Feedback for optimization of design parameters Reinhart-King: BME Liu/Kent: Weill Medical In vitro engineering of scaffolds & cell adhesion study using vascular cells Optimization using stem-cell mediated healing to enhance success of engineered grafts Liu/Kent: Weill Medical In vivo animal model & implantation Future Plan NIH: PAR-06-504 (R01) Enabling Technologies for Tissue Engineering and Regenerative Medicine Projected submission date: 9/10/08 Industry grants Patents Vascular Surgery Lab K. Craig Kent, MD Bo Liu, PhD Rachel Elden Brad Herman, PhD Kaori Kato, MD Rishi Kundi, MD Sebastian Schuble, MD Shirling Tsai, MD Chunjie Wang Dai Yamanouchi, MD, PhD Fan Zhang, MD, PhD Andrew Zohlman Ithaca C.C. Chu, PhD Hua Song, PhD Jun Wu Department of Surgery Research and Sponsored Program Caren A Heller, MD Cornell Intercampus Seed Grant Morgan Seed grant