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Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.

ABSTRACT: Sufficient and sustained anti-thrombogenicity is essential for blood-contacting materials, because blood coagulation and thrombosis caused by platelet adhesion and activation on material surfaces may lead to functional failure and even fatal outcomes. Covalently conjugating antithrombogenic moieties into polymer, instead of surface modifying or blending, can maintain the anti-thrombogenicity of polymer at a high level over a time range. In this study, series of randomly crosslinked, elastic, biodegradable polyurethanes (PU-DPA) were synthesized through a one-pot and one-step method from polycaprolactone (PCL) diol, hexamethylene diisocyanate (HDI) and anti-thrombogenic drug, dipyridamole (DPA). The mechanical properties, hydrophilicity, in vitro degradation, and anti-thrombogenicity of the resultant PU-DPA polymers can be tuned by altering the incorporated DPA amount. The surface and bulk hydrophilicity of the polyurethanes decreased with increasing hydrophobic DPA amount. All PU-DPA polymers exhibited strong mechanical properties and good elasticity. The degradation rates of the PU-DPAs decreased with increasing DPA content in both PBS and lipase/PBS solutions. Covalently incorporating DPA into the polyurethane significantly reduced the platelet adhesion and activation compared to the polyurethane without DPA, and also can achieve sustained anti-thrombogenicity. The PU-DPA films also supported the growth of human umbilical vein endothelial cells. The attractive mechanical properties, blood compatibility, and cell compatibility of this anti-thrombogenic biodegradable polyurethane indicate that it has a great potential to be utilized for blood-contacting devices, and cardiovascular tissue repair and regeneration.

SUBMITTER: Xu C

PROVIDER: S-EPMC6424506 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.

Xu Cancan C Kuriakose Aneetta E AE Truong Danh D Punnakitikashem Primana P Nguyen Kytai T KT Hong Yi Y

Journal of materials chemistry. B 20180807 44

Sufficient and sustained anti-thrombogenicity is essential for blood-contacting materials, because blood coagulation and thrombosis caused by platelet adhesion and activation on material surfaces may lead to functional failure and even fatal outcomes. Covalently conjugating antithrombogenic moieties into polymer, instead of surface modifying or blending, can maintain the anti-thrombogenicity of polymer at a high level over a time range. In this study, series of randomly crosslinked, elastic, bio ...[more]

PMID: 30906556

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Project description: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.

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Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.

Publications

Enhancing anti-thrombogenicity of biodegradable polyurethanes through drug molecule incorporation.

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