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Development of a Hybrid Cryogel-coated Prosthetic Vascular Graft for Delivery of Targeted Gene Therapies
Cindy Huynh1,2, Ting-Yu Shih2, Amruta Samant1, Saif G. Pathan3, David W. Nelson3, David J. Mooney2, Leena Pradhan-Nabzdyk1, Frank W. LoGerfo1
1Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA, 2SUNY Upstate Medical University, Syracuse, NY, USA, 3John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA, 4BioSurfaces, Inc., Ashland, MA

Objective(s):
Anastomotic neo-intimal hyperplasia (ANIH) remains a limiting factor in the long-term success of prosthetic vascular grafts. Understanding of the molecular mechanisms involved in the host response to prosthetic material has set the stage for using this material to deliver siRNA and other modulators of the ANIH-associated transcriptome response, along with antithrombotic agents. To create practical and effective drug delivery from a prosthetic material, we have combined a platform of polyethylene terephthalate (PET) fabric with an applied cryogel carrying the biologic agents, resulting in a bioactive prosthetic graft system.
Methods:
Hybrid grafts were synthesized by cryopolymerization of methacrylated alginate and heparin onto electrospun (ePET), knitted, or woven PET. Arg-Gly-Asp peptides were added to increase cell adhesion. Scanning electron microscopy (SEM) was used to study the microstructure at 1 day, and 2, 4, and 8 weeks. Human aortic endothelial cell (HAoEC) adherence and proliferation were assessed with a resazurin-based assay, and confocal microscopy was used to visualize cell interaction with the graft materials after 24 hours in culture. Heparin activity of the materials in buffer solution was measured using an anti-Xa assay.
Results:
SEM demonstrated large interconnected pores throughout the entire structure for all graft types, with minimal degradation of the cryogel after 8 weeks. HAoECs incorporated, adhered, and proliferated over 7 days for all materials (Figure 1). Anti-Xa assay confirmed continued activity of heparin from all grafts over 7 days.
Conclusions:
We have created a bioactive prosthetic graft system with a biocompatible cryogel polymer coating that allows for cell adherence and growth, with antithrombotic activity. This system allows application of the gel and biologic agents onto PET prior to implantation, and provides flexibility in combining bioengineering and targeted gene therapy approaches to create an improved prosthetic graft adaptable to evolving strategies.


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