In situ forming, metal-adhesive heparin hydrogel surfaces for blood-compatible coating

Durable and blood-compatible coating of metallic biomaterials remains a major issue in biomedical fields despite its long history of development. In this study, in situ forming, metal-adhesive heparin hydrogels were developed to coat metallic substrates to enhance blood compatibility. The hydrogels are composed of metal-adhesive and enzyme-reactive amphiphilic block copolymer (Tetronic-tyramine/dopamine; TTD) and enzyme-reactive heparin derivatives (heparin-tyramine or heparin-polyethylene glycol-tyramine), which are cross-linkable in situ via an enzyme reaction. The combinations of heparin and Tetronic formed hydrogels with relatively high mechanical strengths of 300-5000 Pa within several tens of seconds; this was also confirmed by observing a dried porous structure as coated on a metal surface. The introduction of dopamine to the hydrogel network enhanced the durability of the hydrogel layers coated on metal, such that more than 60% heparin remained for 7 days. Compared to bare metal surfaces, hydrogel-coated metal surfaces exhibited significantly enhanced blood compatibility. Reduced fibrinogen adsorption and platelet adhesion showed that blood compatibility was 3-5-fold-enhanced on coated hydrogel layers than on the bare metal surface. In conclusion, hydrogels containing heparin and dopamine prepared by enzyme reaction have the potential to be an alternative coating method for enhancing blood compatibility of metallic biomaterials.