Introduction of sacrificial bonds to hydrogels to increase defect tolerance during suturing of multilayer vascular grafts

Abstract

Small-caliber vascular grafts used in coronary artery bypass procedures typically fail due to the development of intimal hyperplasia or thrombosis. Our laboratory has developed a multilayered vascular graft with an electrospun polyurethane outer layer with improved compliance matching and a hydrogel inner layer that is both thromboresistant and promotes endothelialization. Initial in vivo studies showed that hydrogel particulates were dislodged from the hydrogel layer of the grafts during suturing. To address this problem, we developed and characterized a new hydrogel formulation that resists damage during suturing. Introduction of sacrificial, hydrogen bonds to poly(ethylene glycol)-based hydrogels via co-polymerization with n-vinyl pyrrolidone (NVP) increased the fracture energy as determined by single edge notch testing. This enhanced defect tolerance resulted in a hydrogel layer that was resistant to suture-induced damage with no dislodged particles observed. Importantly, the incorporation of NVP did not affect the thromboresistance, bioactivity, or biostability of the hydrogel layer. In addition to eliminating complications due to hydrogel particle generation in our multilayer graft design, this defect tolerant hydrogel formulation has broad potential use in many cardiovascular and soft tissue applications.

Statement of significance: Small-caliber vascular grafts used in coronary artery bypass procedures typically fail due to development of intimal hyperplasia or thrombosis. Our laboratory has developed a multilayered vascular graft with an electrospun polyurethane outer layer with improved compliance matching and a hydrogel inner layer that is both thromboresistant and promotes endothelialization. However, hydrogel particulates were dislodged from the hydrogel layer during suturing in vivo. This work describes a hydrogel formulation based on poly(ethylene glycol) that is resistant to suture-induced damage. The introduction of sacrificial, hydrogen bonds by co-polymerization with n-vinyl pyrrolidone (NVP) resulted in an increase fracture energy without affecting the thromboresistance, bioactivity, or biostability. This defect-tolerant hydrogel formulation and the methodology to assess hydrogel defect tolerance has broad potential use in cardiovascular and soft tissue applications.

Keywords: Hydrogel; Sacrificial bonds; Suture damage resistance; Thromboresistant coating; Vascular graft.