Abstract 132: Application of a Cryogel-Coated Prosthetic Vascular Graft Material for Delivery of Targeted Gene Therapies in a Rabbit Model

Objectives: Long-term success of prosthetic grafts (PG) in peripheral arterial disease is limited by development of anastomotic neointimal hyperplasia. We have constructed a bioactive prosthetic graft material (BPGM) capable of delivering biologic agents in vitro, and evaluate our BPGM in vivo with a rabbit carotid interposition bypass model. Methods: We synthesized our BPGM by cryopolymerization of RGD with methacrylated alginate and heparin, coating 1.5cm by 2mm electrospun PET (ePET) grafts, and dipcoating in fluorescent siRNA for 3 hours. Three rabbits received bare ePET and 3 received cryogel-coated ePET for a carotid interposition bypass (Figure 1). After 24 hours, bypass patency was assessed, and cell toxicity of the proximal anastomosis, mid-graft, and distal anastomosis examined with H&E staining. Confocal microscopy was used to visualize fluorescence, correlating with ability to deliver siRNA in vivo. Results: Graft patency was equal between groups, with no increased cell toxicity in rabbits receiving cryogel-coated ePET. Confocal microscopy demonstrated no difference in retained fluorescence between rabbits receiving cryogel-coated or bare ePET, and no increased transfection of cells at 24 hours (Figure 2). Conclusion: Creation of the optimal PG demands a material that is biocompatible, responsive, and nonthrombogenic. We have constructed a modified PG capable of in vitro delivery of targeted gene therapies, with comparable patency and biocompatibility in our large animal model. Additional optimization to achieve predictable and sustained release is needed to validate this as an effective and practical method to deliver biologic agents in vivo.