title: Surface Modification of Biodegradable Polymers towards Better Biocompatibility and Lower Thrombogenicity.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rudolph
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Teske
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Illner
authors.affiliation: Department of Transfusion Medicine, Rostock University Medical Center, Ernst-Heydemann-Strasse 6, D-18057, Rostock, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Kiefel
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Sternberg
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Grabow
authors.affiliation: Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, D-18057, Rostock, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.affiliation: Institute for Biomedical Engineering, Rostock University Medical Center, Friedrich-Barnewitz-Strasse 4, D-18119, Rostock, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Hovakimyan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry*; D002460:Cell Line; D003331:Coronary Vessels / Q000187:drug effects; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005347:Fibroblasts / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry*; D015607:Stents / Q000009:adverse effects; D013499:Surface Properties / Q000187:drug effects*; D013927:Thrombosis / Q000139:chemically induced*
chemical_list: D001672:Biocompatible Materials; D011108:Polymers