Department of Molecular Science and Technology, Ajou University, San 5, Woncheon, Yeoungtong, Suwon 443-749, South Korea.
Colloids Surf B Biointerfaces. 2012 Nov 1;99:102-7. doi: 10.1016/j.colsurfb.2011.10.047. Epub 2011 Nov 2.
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.
尽管金属生物材料的耐用且血液相容的涂层的发展已有很长的历史，但它仍然是生物医学领域的一个主要问题。在这项研究中，开发了原位形成的、金属附着的肝素水凝胶，以涂覆金属基底以增强血液相容性。水凝胶由金属附着和酶反应性两亲嵌段共聚物（Tetronic-酪胺/多巴胺；TTD）和酶反应性肝素衍生物（肝素-酪胺或肝素-聚乙二醇-酪胺）组成，它们可以通过酶反应原位交联。肝素和 Tetronic 的组合在几十秒内形成具有相对较高机械强度（300-5000 Pa）的水凝胶；这也通过观察涂覆在金属表面上的干燥多孔结构得到证实。将多巴胺引入水凝胶网络增强了涂覆在金属上的水凝胶层的耐久性，使得超过 60%的肝素在 7 天内保持不变。与裸金属表面相比，水凝胶涂覆的金属表面表现出显著增强的血液相容性。纤维蛋白原吸附和血小板黏附的减少表明，涂覆的水凝胶层的血液相容性比裸金属表面增强了 3-5 倍。总之，通过酶反应制备的含有肝素和多巴胺的水凝胶有可能成为增强金属生物材料血液相容性的替代涂层方法。
