Event Abstract Back to Event An external shape memory mesh to prevent dialysis graft failure Timothy Boire1*, William C. Kaplan1*, Christy M. Guth2, 3*, Eric S. Wise2*, David Shaffer3*, Colleen M. Brophy2* and Hak-Joon Sung1* 1 Vanderbilt University, Biomedical Engineering, United States 2 Vanderbilt University, Division of Vascular Surgery, United States 3 Vanderbilt University, Division of Kidney & Pancreas Transplantation, United States Introduction: Hemodialysis is the primary lifeline for patients with end-stage renal disease, but arteriovenous graft (AVG) failure imposes significant morbidity, mortality, and financial impositions. Failure rates of 50% after 1 year and 75% after 2 years are reported in hemodialysis patients that utilize AVGs. Stenosis at the venous anastomosis ultimately leads to compromised blood flow, necessitating vascular interventions (e.g. balloon angioplasty or stents) or re-do access surgeries. Major financial impositions ensue for patients, insurers, and dialysis clinics, while blemishing hospital records with unwanted, expensive patient readmissions. The leading cause of failure at the venous anastomosis is neointimal formation triggered by venous responses to surgical injury and increased hemodynamic stresses experienced in the high pressure, high flow arterial circulation. We are developing an external mesh that can minimize neointimal formation by providing mechanical support to the thin venous walls and promoting outward instead of inward vein remodeling in this environment. Existing external mesh supports applied in other settings, such as to saphenous vein grafts in heart bypass grafting surgeries, have demonstrated some promise but cannot be readily applied in hemodialysis vascular access surgeries because of the geometric complexity of the venous anastomosis, the foci of neointimal formation. Our novel shape memory polymers (SMPs) enable facile encompassing of the anastomosis that is most critical to maintaining vein patency. Preliminary data in an ex vivo model with human saphenous veins (HSV) indicates an ability of these external supports to reduce neointimal formation and, in turn, obviate the subsequent adverse clinical repercussions. Materials and Methods: Meshes comprised of x%poly(ε-caprolactone)-co-y%(α-allyl carboxylate ε-caprolactone) SMPs were fabricated via a 3D printing mold creation method and photocrosslinking [1]. HSVs were obtained from CABG patients at VUMC according to IRB protocols and treated with external supports in a well-established ex vivo model [2]. After 14 days, tissues were fixed in 10% formalin, paraffin-embedded, sectioned, and stained with elastic to assess morphometry for treated versus untreated (day 14) and baseline (day 0) controls. Results and Discussion: Fabricated shape memory external supports displayed uniform porosity and thickness, and were able to be molded around constructed anastomoses at body temperature with ease. Application of these meshes to HSV samples reduced intimal and medial thicknesses after 14 days of ex vivo culture compared to untreated controls (Figure 1). Figure 1. SMP-treated HSVs (right) reveal less intimal thickening (black bars) than the untreated group (left). Conclusion: External SMP meshes were fabricated that are capable of robustly encompassing the venous anastomosis and reducing neointimal formation in HSVs. This demonstrates a promising effect of this support to improve vein graft patency in surgical procedures exposing veins to the arterial circulation such as in hemodialysis access and CABG surgeries. Unlike other materials, these SMPs can readily encompass venous anastomoses without sutures, reducing surgery times, risk of infection and suture dehiscence. Ongoing work involves testing venous responses in an ex vivo flow model with artery-mimetic pressure and flow [3], characterizing immunohistochemical and VSMC responses to these materials, and selecting the most promising prototype for a porcine dialysis graft model.
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