Arterio-venous Fistula Scaffold Jonathan Jaffery Ph D

Arterio-venous Fistula Scaffold Jonathan Jaffery, Ph. D – School of Medicine Naomi Chesler, Ph. D – Dept. of Biomedical Engineering Kristyn Masters, Ph. D – Dept. of Biomedical Engineering Brenda Ogle, Ph. D – Dept. of Biomedical Engineering Karen Chen Holly Liske Laura Piechura Kellen Sheedy

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Presentation Overview Background information n Problem statement n Design criteria n Overview of four materials n Testing n Matrix n Future work n

Background - Hemodialysis n Renal failure n 300, 000+ Americans n To cleanse the blood n Methods ¨ Catheter ¨ Graft ¨ Arterio-venous (AV) fistula

Background – Fistula Maturation n Connect vein and artery n Increased blood flow → Vein arterialization n Advantages ¨ Low infection rates ¨ High blood flow rate ¨ Low incidence of clotting Figure 1: Arterio-venous (AV) fistula.

Problem Statement n 45% success rate of current AV fistula n Veins collapse during hemodialysis n External scaffolding to prevent vein collapse n Shorter maturation period

Design Criteria n Injectable liquid n Polymerizable in situ n Adhere and tether to the vein n Withstand puncture and tension n Biocompatibility

Alginate ¨ Properties n n n Extracted from seaweed Linear branching copolymers Crosslinked by divalent cations (i. e. Ca 2+) ¨ Applications n n n Prosthetics Pharmaceuticals Burn dressing ¨ Degradation n Oxidation over time ¨ Advantages/Disadvantages n n + : immediate polymerization - : difficult to polymerize in situ

Pluronic F-127 ¨ Properties n n Triblock copolymer Thermoreversible polymerization ¨ Applications n n n Drug and peptide delivery Artificial skin Temporary vascular occlusion ¨ Degradation n Mechanical perturbation ¨ Advantages/Disadvantages n n + : polymerizes at physiological temperatures - : resulting gel is semi-solid

Polyethylene glycol diacrylate (PEG-DA) ¨ Properties n n Covalently cross-linked polymers PEG-DA + I-2959 photoinitiator + UV light ¨ Applications n n Polymer cross-linking Flexible plastics ¨ Degradation n n Resistant to hydrolysis and enzyme degradation Modified with concentration and copolymerization ¨ Advantages/Disadvantages n n + : firm polymer - : requires UV exposure to polymerize

Fibrin gel ¨ Properties n n Fibrinogen zymogen activated by thrombin Meshwork involved in blood clotting ¨ Applications n n Vascular sealant in surgery Tissue engineering of cartilage ¨ Degradation n Fibrinolysis ¨ Advantages/Disadvantages n n + : employs biological processes - : requires multiple polymerizing agents

Adhesion Test Figure 2: Relative strengths of the tissue-biomaterial adhesion for alginate, fibrin gel, PEG-DA, and Pluronic F-127 on bovine aorta tissue.

Puncture Test Alginate Fibrin gel Pluronic F-127 PEG-DA Figure 3: Material response to puncture with 18 G needle on porcine aorta tissue.

Material Matrix Materials Criterion Rank Adhesiveness Alginate Fibrin Gel PEG-DA Pluronic F 127 0. 50 2 5 4 1 Polymerization Method 0. 20 2 4 1 5 Elasticity 0. 20 4 3 3 4 Self-Sealing 0. 05 1 4 4 1 Biodegradable 0. 05 3 4 3 2 Totals 1. 0 2. 40 4. 30 3. 15 2. 45

Future Work n Optimize properties of fibrin gel n Test material in vitro Adhesion test ¨ Puncture test ¨ Perfusion chamber ¨ n Test material in vivo ¨ Pig model system

References Ching, A. L. , Liew, C. V. , Heng, P. W. S. and Chan, L. W. 2008. Impact of cross-linker on alginate matrix integrity and drug release. Int’l J. Pharmaceutics. Escobar-Chavez, J. J. , Lopez-Cervantez, M. , Maik, A. , Kalia, Y. N. , Quintanar-Guerrero, D. , Ganem-Quintanar, A. 2006. Applications of thermoreversible pluronic F-127 gels in pharmaceutical formulations. Journal of Pharmacy and Pharmaceutical Sciences. 9 (3): 339 -358. Eyrich, D. , Brandl, F. , Appel, B. , Wiese, H. , Maier, G. , Wenzel, Ml, Staudenmair, R. , Goepferich, A. , Blunk, T. 2007. Long-term stable fibrin gels for cartilage engineering. Biomaterials 28: 55 -65. Mao, Jeremy. 2006. Poly(ethylene glycol)-diacrylate crosslinked hydrogels comprising adipogenic mesenchymal stem cells. International Patent Application PCT/US 2005/023318. Ohta, S. , Nitta, N. , Takahasi, M. , Sonoda, A. , Tanaka, T. , Yamasaki, M. , Furukawa, A. , Takazakura, R. , Murata, K. , Sakamoto, T. , Kushibiki, T. , Tabata, Y. 2006. Pluronic F-127: application in arterial embolization. Journal of vascular and interventional radiology. 17 (3): 533 -539. Polyethylene glycol diacrylate. http: //chemicalland 21. com/industrialchem/functional%20 Monomer/POLYETHYLENE%20 GLYCOL%20 DI ACRYLATE. htm. <4 March 2008> Raymond, J. , Metcalfe, A. , Salazkin, I. , Schwarz, A. 2004. Temporary vascular occlusion with poloxamer 407. Biomaterials 25 (18): 3983 -3989.