In Vitro and In Vivo biocompatibility study of fluorinated polyphosphazene coatings for blood-contacting medical devices

氟化聚磷腈涂层在血液接触医疗器械中的体外和体内生物相容性研究

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作者:Bryan M Gregorits,Yi Wu,Chen Chen,Eric Yeager,Myddelton C Parker,Isabel Martinez,Meghan L Lancaster,Chad Schmiedt,Hitesh Handa,Harry R Allcock,Christopher A Siedlecki,Li-Chong Xu

Abstract

Implant-induced thromboembolic events are the most common complication of blood contacting medical devices. Coatings are a promising approach to improve the biocompatibility of current biomaterials and devices. Poly[bis(trifluoroethoxy) phosphazene] (TFE) has been demonstrated to be biocompatible, anti-inflammatory, and antithrombogenic as a device coating over the past decades; however, its inherently poor mechanical properties make applications in medical devices challenging, especially regarding potential detachment from devices. Our previous work developed a new fluorinated polyphosphazene, poly[bis(octafluoropentoxy) phosphazene] (OFP), and incorporated allylphenoxy side groups to the P-N backbone to make the polymer crosslinkable (X-OFP). In this study, we applied this X-OFP coating on central venous catheters and investigated the surface properties and biocompatibility of the coatings. In vitro and in vivo studies demonstrated that X-OFP has a similar antithrombogenic performance as TFE, but its mechanical properties including adhesion strength of coating-to-substrate are significantly improved, thereby enhancing the stability of the coating. The success of X-OFP will provide a platform to incorporate other side groups to the polymer backbones and generate new fluorinated polyphosphazene polymers having improved biocompatibility and mechanical properties for coating applications in blood-contacting medical devices. STATEMENT OF SIGNIFICANCE: Implant-induced thrombosis is a major complication of blood-contacting medical devices. This study demonstrated a new fluorinated polyphosphazene coating suitable for the medical device with the significant improvement of the biocompatibility of catheters. Compared to the traditional fluorinated polyphosphazene coating, poly[bis(trifluoroethoxy) phosphazene] (TFE), crosslinkable poly[bis(octafluoropentoxy) phosphazene] (X-OFP) contains a higher amount of fluorocarbon content with the octafluoropentoxy side group and is crosslinkable with the allylphenoxy side group. TFE and X-OFP were applied on central venous catheters as coatings. In vitro and in vivo studies demonstrated that X-OFP has a similar antithrombogenic performance as TFE, but its mechanical properties including adhesion strength of coating-to-substrate are significantly improved, thereby enhancing the stability of the coating.

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