Blood compatibility assessment of polymers used in drug eluting stent coatings

Abstract

Differences in thrombosis rates have been observed clinically between different drug eluting stents. Such differences have been attributed to numerous factors, including stent design, injury created by the catheter delivery system, coating application technologies, and the degree of thrombogenicity of the polymer. The relative contributions of these factors are generally unknown. This work focuses on understanding the thrombogenicity of the polymer by examining mechanistic interactions with proteins, human platelets, and human monocytes of a number of polymers used in drug eluting stent coatings, in vitro. The importance for blood interactions of adsorbed albumin and the retention of albumin was suggested by the data. Microscopic imaging and immunostaining enhanced the interpretation of results from the lactate dehydrogenase cell counting assay and provided insight into platelet interactions, total quantification, and morphometry. In particular, highly spread platelets may be surface-passivating, possibly inhibiting ongoing thrombotic events. In many of the assays used here, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) showed a differentiated protein deposition pattern that may contribute to the explanation of the consistently thromboresistant blood-materials interaction for fluororpolymers cited in literature. These results are supportive of one of several possible factors contributing to the good thromboresistant clinical safety performance of PVDF-HFP coated drug eluting stents.

Very Late Pathological Responses to Cobalt–Chromium Everolimus‐Eluting, Stainless Steel Sirolimus‐Eluting, and Cobalt–Chromium Bare Metal Stents in Humans

“…PEVA (poly[ethylene‐co‐vinyl acetate]) and PBMA (poly[ n ‐butyl methacrylate]) were used on SS‐SESs, whereas PVDF‐HFP (poly[vinylidene fluoride‐co‐hexafluoropropylene]) is the polymer used in CoCr‐EESs. The PVDF‐HFP “fluoropolymer” used on CoCr‐EESs adsorbs and retains albumin compared with BMSs, and this is thought to help minimize platelet adhesion and activation and leukocyte recruitment . In a preclinical study, other fluoropolymer‐coated metallic stents, in the absence of antiproliferative drugs, showed significantly less inflammation and less neointima than BMSs at 28 and 90 days in the coronary arteries of pigs .…”

Vascular response and intrastent thrombus in the early phase after drug‐eluting versus bare‐metal stent implantation in patients with ST‐segment elevation myocardial infarction: An observational, single‐center study

“…In contrast, the polymer in Xience‐EES was poly( n ‐butyl methacrylate) (PBMA) encapsulated by a poly(vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP). PVDF‐HFP (used on Xience‐EES) retained more albumin and platelet interaction behavior than PBMA and polystyrene‐ b ‐polyisobutylene‐ b ‐polystyrene (used on Taxus Liberté‐PES) . Thus, the difference in protein and surface materials may be attributed to the different properties in antithrombogenicity between the two DES.…”

“…The polymer in DES is a carrier of eluted drug and has several characteristics that improve biocompatibility of the stent through anti-inflammatory and antithrombotic effects. [29][30][31][32] Previous studies demonstrated that polymer coating provides thromboresistance through the modification of surface properties such as electrostatic forces, hydrophilic interaction, and roughness. [33][34][35] In particular, the fluoropolymer in Xience-EES was designed to have better biocompatibility for blood and vascular tissues compared with that in older stents.…”

Preface: In Focus Issue on Blood–Biomaterial Interactions

“…In this context, the report of Cornelius et al 1 on the interaction of lipoproteins with bare and polyethylene glycol-modified polyurethane surfaces can be highlighted, as well as the two reports pointing to differences in plasma protein adsorption and activation at different surfaces. 2,9 Szott et al 2 and Gupta et al 3 also report differences in platelet activation between different surfaces. The two latter studies contribute to the growing body of evidence that platelet spreading may not be representative of other activation phenomena.…”