Water-soluble argatroban for antithrombogenic surface coating of tissue-engineered cardiovascular tissues

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Vol. 99B; no. 2; pp. 420 - 430
• Main Authors: Nakayama, Yasuhide, Yamaoka, Saori, Yamanami, Masashi, Fujiwara, Megumi, Uechi, Masami, Takamizawa, Keiichi, Ishibashi-Ueda, Hatsue, Nakamichi, Marie, Uchida, Kingo, Watanabe, Taiji, Kanda, Keiichi, Yaku, Hitoshi
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.11.2011; Wiley-Blackwell
• Subjects: Adsorption; Animals; anionic; antithrombogenic coating; aqueous coating; argatroban; Biological and medical sciences; Biotechnology; Blood Vessel Prosthesis; Coated Materials, Biocompatible - chemistry; Coloring Agents - chemistry; Coloring Agents - pharmacology; Connective Tissue - pathology; Dogs; Female; Fundamental and applied biological sciences. Psychology; Health. Pharmaceutical industry; Heart Valve Prosthesis; Humans; Industrial applications and implications. Economical aspects; Ions; Materials Testing; Medical sciences; Miscellaneous; Models, Chemical; Pipecolic Acids - chemistry; Solubility; surface modification; Surface Properties; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Technology. Biomaterials. Equipments; Tissue Engineering - methods; Water - chemistry; Water; Coating material; Tissue engineering; surface modification; Argatroban; anionic; Biomaterial; Coatings; antithrombogenic coating; Surface treatment; Biomedical engineering; aqueous coating
• ISSN: 1552-4973; 1552-4981; 1552-4981
• DOI: 10.1002/jbm.b.31914

Argatroban is a powerful synthetic anticoagulant, but due to its water‐insoluble nature, it is unsuitable for use as a coating material to reduce the thrombogenic potential of natural or tissue‐engineered blood‐contacting cardiovascular tissues. On the other hand, anionic compounds could adsorb firmly onto connective tissues. Therefore, in this study, an anionic form of argatroban was prepared by neutralization from its alkaline solution, dialysis, and freeze‐drying. The subsequently obtained argatroban derivative could be easily dissolved in water. Analysis of the surface chemical composition showed that the water‐soluble argatroban (WSA) could be adsorbed on the entire surface of tissue‐engineered connective tissue sheets composed mainly of collagen. Adsorption was achieved on immersion of the tissue‐engineered connective tissue sheet in a saline/WSA solution for only 30 s without any change in the mechanical properties of the tissue‐engineered sheets. Complete surface adsorption (ca., 1 mg/cm2) was obtained at WSA concentrations of over 5 mg/mL. WSA adsorption was maintained for at least 7 days with rinsing. Blood coagulation was significantly prevented on the WSA‐adsorbed surfaces in acute in vitro experiments. The coating was applied to in vivo tissue‐engineered vascular grafts (biotubes) or tri‐leaflet tissues (biovalves) under development, ensuring a high likelihood of nonthrombogenicity of their blood‐contacting surfaces with high patency, at least in the subchronic phase. It appears that WSA satisfies the initial requirements for a biocompatible aqueous coating material for use in natural or tissue‐engineered tissues. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 99B: 420–430, 2011.