title: In situ forming, metal-adhesive heparin hydrogel surfaces for blood-compatible coating.
abstract: 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.
authors.affiliation: Department of Molecular Science and Technology, Ajou University, San 5, Woncheon, Yeoungtong, Suwon 443-749, South Korea.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Joung
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: You
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Park
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Go
authors.forename: Ki Dong
authors.initials: KD
authors.lastname: Park
mesh_terms: D000269:Adhesives / Q000138:chemical synthesis* / Q000494:pharmacology; D000327:Adsorption; D001769:Blood; D001792:Blood Platelets / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis* / Q000494:pharmacology; D004298:Dopamine / Q000737:chemistry; D055119:Elastic Modulus; D005340:Fibrinogen / Q000737:chemistry; D006493:Heparin / Q000031:analogs & derivatives*; D006735:Horseradish Peroxidase / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis*; D006861:Hydrogen Peroxide / Q000737:chemistry; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D010973:Platelet Adhesiveness / Q000187:drug effects; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013193:Stainless Steel / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D014439:Tyramine / Q000737:chemistry
chemical_list: D000269:Adhesives; D020099:Coated Materials, Biocompatible; D020100:Hydrogels; D013501:Surface-Active Agents; D020442:Poloxamer; D013193:Stainless Steel; D011092:Polyethylene Glycols; D005340:Fibrinogen; D006493:Heparin; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D004298:Dopamine; D014439:Tyramine