Materials 2012, 5(10), 1986-2002; doi:10.3390/ma5101986
Article

Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial

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Received: 11 October 2012; in revised form: 16 October 2012 / Accepted: 18 October 2012 / Published: 23 October 2012
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 without causing toxicity and inflammation. However, it should be noted that the test samples prepared by the cross-linking in the presence of acetone/water mixtures containing 70, 75, and 95 vol % of acetone slightly inhibit the metabolic activity of viable ARPE-19 cultures, probably due to the alteration in the ionic interaction between the medium nutrients and polysaccharide biomaterials. In summary, the water content, mechanical strength and RPE cell proliferative capacity strongly depends on the solvent composition for carbodiimide cross-linking of HA materials.
Keywords: hyaluronic acid; carbodiimide; cross-linking; solvent composition; ophthalmic biomaterial
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MDPI and ACS Style

Lai, J.-Y. Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial. Materials 2012, 5, 1986-2002.

AMA Style

Lai J-Y. Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial. Materials. 2012; 5(10):1986-2002.

Chicago/Turabian Style

Lai, Jui-Yang. 2012. "Solvent Composition is Critical for Carbodiimide Cross-Linking of Hyaluronic Acid as an Ophthalmic Biomaterial." Materials 5, no. 10: 1986-2002.


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