Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity

• Published in: PloS one Vol. 10; no. 12; p. e0142075
• Main Authors: Rudolph, Andreas, Teske, Michael, Illner, Sabine, Kiefel, Volker, Sternberg, Katrin, Grabow, Niels, Wree, Andreas, Hovakimyan, Marina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-12-2015; Public Library of Science (PLoS)
• Subjects: Acids; Addition polymerization; Adhesion; Adhesion tests; Ammonia; Animals; Biocompatibility; Biocompatible Materials - administration & dosage; Biocompatible Materials - chemistry; Biodegradability; Biodegradable materials; Biodegradation; Biomedical engineering; Biomedical materials; Biomolecules; Caprolactone; Cardiovascular disease; Care and treatment; Cell adhesion & migration; Cell growth; Cell Line; Coatings; Coronary artery; Coronary Vessels - drug effects; Cytology; Cytotoxicity; Diagnosis; Drug delivery; Drug-Eluting Stents - adverse effects; Drugs; Endothelial cells; Engineering; Ethylenediamine; Ethylenediamines; Fibroblasts; Fibroblasts - drug effects; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Implants; In vivo methods and tests; Life assessment; Mice; Microscopy; Poly(L-lactide); Polylactic acid; Polymer coatings; Polymers; Polymers - administration & dosage; Polymers - chemistry; Restenosis; Stents; Stents - adverse effects; Surface Properties - drug effects; Surgical implants; Thromboembolism; Thrombosis; Thrombosis - chemically induced; Toxicity; Umbilical vein; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0142075

Drug-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.
Five 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.
Both 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.
Surface 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.