In vitro and ex vivo hemocompatibility of off-the-shelf modified poly(vinyl alcohol) vascular grafts

Abstract

Synthetic small diameter vascular grafts with mechanical properties of native arteries, resistance to thrombosis and capacity to stimulate in situ endothelialization are an unmet clinical need. Poly(vinyl alcohol) hydrogel (PVA) is an excellent candidate as a vascular graft due to its tunable mechanical properties. However, the hydrophilicity and bio-inertness of PVA prevents endothelialization in vivo. We hypothesize that the modification of PVA with biomolecules and topographies creates a hemocompatible environment that also enhances bioactivity. PVA modified with fibronectin, RGDS peptide, cyclicRGD (cRGD) peptide, or heparin provided cell-adhesion motifs, which were confirmed by detection of nitrogen through X-ray photoelectron spectroscopy. Protein-and peptide-modified surfaces showed a slight increase in human vascular endothelial cell proliferation over unmodified PVA. With the exception of fibronectin modification, modified surfaces showed in vitro hemocompatibility comparable with unmodified PVA. To further improve bioactivity, cRGD-PVA was combined with gratings and microlens topographies. Combined modifications of 2µm gratings or convex topography and cRGD significantly improved human vascular endothelial cell viability on PVA. In vitro hemocompatibility testing showed that topography on cRGD-PVA did not significantly trigger an increase of platelet adhesion or activation compared with unpatterned PVA. Using the more physiologically relevant ex vivo hemocompatibility testing, all PVA grafts tested showed similar platelet adhesion to ePTFE and significantly lower platelet accumulation compared to collagen-coated ePTFE grafts. The

Surface modification of polyvinyl alcohol (PVA)/polyacrylamide (PAAm) hydrogels with polydopamine and REDV for improved applicability

“…Although the water contact angle was increased by the PDA and PDA‐REDV coatings, the surfaces of both coated hydrogels were still highly hydrophilic. These results were in accordance with the previous reports …”

“…Undoubtedly, current vascular grafts do not meet these clinical requirements regarding high compliance yet. Therefore, researchers over the globe have been conducting more studies concerning the development of the innovative small diameter vascular grafts with high compliance, and biomedical hydrogels are appropriate candidates for their favorable elasticity …”

“…Therefore, researchers over the globe have been conducting more studies concerning the development of the innovative small diameter vascular grafts with high compliance, and biomedical hydrogels are appropriate candidates for their favorable elasticity. 58 Biomedical hydrogels show natural anti-fouling properties due to the super hydrophilicity, which leads to fewer proteins and cells adhesion onto the surface. 62 However, the data for long-term antithrombotic effects in vivo have not been sufficient and convincing.…”

Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix

“…While these results are encouraging, none of these coatings are inherently anti-thrombogenic. In fact, hemo-compatibility of collagen IV and fibronectin has been examined by other groups, and both were found to activate platelets in the absence of anti-platelet therapies such as hyaluronic acid or heparin [12,13]. …”

Bioactive Anti‐Thrombotic Modification of Decellularized Matrix for Vascular Applications

“…This quantity of platelets is similar to the amount of platelets that accumulated on the common clinically-utilized vascular graft material expanded polytetrafluoroethylene (ePTFE) in prior studies by our group using this model. [41] Despite the low platelet accumulation of unmodified SIS, the dual-modified SIS+TM+Hep did demonstrate a significant reduction in platelet accumulation, highlighting the potent anti-thrombotic effect of the dual modification.…”