Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

Abstract

PurposeDrug-eluting stents (DES) based on permanent polymeric coating matrices have been introduced to overcome the in stent restenosis associated with bare metal stents (BMS). A further step was the development of DES with biodegradable polymeric coatings to address the risk of thrombosis associated with first-generation DES. In this study we evaluate the biocompatibility of biodegradable polymer materials for their potential use as coating matrices for DES or as materials for fully bioabsorbable vascular stents.Materials and MethodsFive different polymers, poly(L-lactide) PLLA, poly(D,L-lactide) PDLLA, poly(L-lactide-co-glycolide) P(LLA-co-GA), poly(D,L-lactide-co-glycolide) P(DLLA-co-GA) and poly(L-lactide-co-ε-caprolactone), P(LLA-co-CL) were examined in vitro without and with surface modification. The surface modification of polymers was performed by means of wet-chemical (NaOH and ethylenediamine (EDA)) and plasma-chemical (O2 and NH3) processes. The biocompatibility studies were performed on three different cell types: immortalized mouse fibroblasts (cell line L929), human coronary artery endothelial cells (HCAEC) and human umbilical vein endothelial cells (HUVEC). The biocompatibility was examined quantitatively using in vitro cytotoxicity assay. Cells were investigated immunocytochemically for expression of specific markers, and morphology was visualized using confocal laser scanning (CLSM) and scanning electron (SEM) microscopy. Additionally, polymer surfaces were examined for their thrombogenicity using an established hemocompatibility test.ResultsBoth endothelial cell types exhibited poor viability and adhesion on all five unmodified polymer surfaces. The biocompatibility of the polymers could be influenced positively by surface modifications. In particular, a reproducible effect was observed for NH3-plasma treatment, which enhanced the cell viability, adhesion and morphology on all five polymeric surfaces.ConclusionSurface modification of polymers can provide a useful approach to enhance their biocompatibility. For clinical application, attempts should be made to stabilize the plasma modification and use it for coupling of biomolecules to accelerate the re-endothelialization of stent surfaces in vivo.

Long-term results of stenting unprotected left main of the left coronary artery in patients with a stable ischemic heart disease using different types of stents with antiproliferative coating

“…По результатам нашего наблюдения, основными причинами, определившими лучшие результаты стентирования незащищенного ствола ЛКА при использовании стентов II и III поколения, стали устранение неблагоприятного воздействия постоянного полимерного покрытия на стенку сосуда и уменьшение профиля платформы стента. Это привело к снижению риска мальаппозиции стента и улучшению его эндотелизации [16,17]. Улучшение результатов стентирования отмечено на фоне изменения популяции пациентов, их возраста и исходных клинических характеристик.…”

Dialysis-Induced Cardiovascular and Multiorgan Morbidity

“…For example, minimization of the blood-air interface in the extracorporeal circuit is possible by combining a very short circuit with a blood cassette and avoidance of the venous bubble trap. 130,131 Incorporation of antithrombotic agents within the core polymer bulk or on the surface of dialyzer fibers and blood lines is also being explored, 132,133 as is the use of citric-acidified bicarbonate dialysate as an adjunct to antithrombotic-treated polymer. [134][135][136] Finally, methods are being developed to prevent or reduce microbubble formation within the extracorporeal circuit.…”

Mutual influence of incorporated drugs in a dual drug delivery coating for cardiovascular applications

“…At first the polymer was activated via oxygen (O 2 )-plasma according to Rudolph et al [12] followed by an incubation in a BS 3 phosphate buffered saline solution (PBS, pH 7.6) for 30 min at room temperature. After rinsing with PBS and water samples were immersed in PBS with VEGF (1 µg/mL) for 1 h at room temperature.…”

“…As model drug for bulk incorporation we used fluorescein diacetate (FDAc) with diffusion and distribution coefficients similar to paclitaxel [11]. To immobilize VEGF we generated functional groups on the polymer surface via an established oxygen plasma procedure which also improves hemocompatibility of PLLA-co-CL [12]. The immobilization of VEGF occurs by the formation of ester bonds and the release of VEGF by their hydrolysis [13].…”