Mussel-inspired one-step adherent coating rich in amine groups for covalent immobilization of heparin: hemocompatibility, growth behaviors of vascular cells, and tissue response

ACS Appl Mater Interfaces. 2014 Aug 27;6(16):14608-20. doi: 10.1021/am503925r. Epub 2014 Aug 18.

Abstract

Heparin, an important polysaccharide, has been widely used for coatings of cardiovascular devices because of its multiple biological functions including anticoagulation and inhibition of intimal hyperplasia. In this study, surface heparinization of a commonly used 316L stainless steel (SS) was explored for preparation of a multifunctional vascular stent. Dip-coating of the stents in an aqueous solution of dopamine and hexamethylendiamine (HD) (PDAM/HD) was presented as a facile method to form an adhesive coating rich in primary amine groups, which was used for covalent heparin immobilization via active ester chemistry. A heparin grafting density of about 900 ng/cm(2) was achieved with this method. The retained bioactivity of the immobilized heparin was confirmed by a remarkable prolongation of the activated partial thromboplastin time (APTT) for about 15 s, suppression of platelet adhesion, and prevention of the denaturation of adsorbed fibrinogen. The Hep-PDAM/HD also presented a favorable microenvironment for selectively enhancing endothelial cell (EC) adhesion, proliferation, migration and release of nitric oxide (NO), and at the same time inhibiting smooth muscle cell (SMC) adhesion and proliferation. Upon subcutaneous implantation, the Hep-PDAM/HD exhibited mitigated tissue response, with thinner fibrous capsule and less granulation formation compared to the control 316L SS. This number of unique functions qualifies the heparinized coating as an attractive alternative for the design of a new generation of stents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bivalvia*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Coated Materials, Biocompatible / adverse effects
  • Coated Materials, Biocompatible / chemistry*
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Endothelium, Vascular / cytology
  • Heparin
  • Humans
  • Materials Testing
  • Platelet Adhesiveness / drug effects
  • Rabbits
  • Stainless Steel
  • Stents / adverse effects

Substances

  • Coated Materials, Biocompatible
  • Stainless Steel
  • Heparin