Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial 英文参考文献.docVIP

Materials 2012, 5, 1986-2002; doi:10.3390/ma5101986 OPEN ACCESS materials ISSN 1996-1944 /journal/materials Article Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial Jui-Yang Lai 1,2,3 1 Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; E-Mail: jylai@.tw; Tel.: +886-3-211-8800, ext. 3598; Fax: +886-3-211-8668 2 Biomedical Engineering Research Center, Chang Gung University, Taoyuan 33302, Taiwan 3 Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan Received: 11 October 2012; in revised form: 16 October 2012 / Accepted: 18 October 2012 / Published: 23 October 2012 Abstract: Hyaluronic acid (HA) is one of the most important ophthalmic biomaterials, while also being used for tissue engineering and drug delivery. Although chemical cross-linking is an effective way to improve the material performance, it may as a consequence be detrimental to the living cells/tissues. Given that the cross-linking efficiency is mediated by the solvent composition during the chemical modification, this study aims to explore the stability and biocompatibility of carbodiimide cross-linked HA in relation to material processing conditions by varying the acetone/water volume ratio (from 70:30 to 95:5) at a constant 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) concentration of 100 mM. Our results indicated that after the EDC treatment in the presence of an acetone/water mixture (85:15, v/v), the HA hydrogel membranes have the lowest equilibrium water content, the highest stress at break and the greatest resistance to hyaluronidase digestion. Live/Dead assays and pro-inflammatory cytokine expression analyses showed that the cross-linked HA hydrogel membranes, irrespective of the solvent composition, are compatible with human RPE cell lines