Tailoring Stimuli Responsiveness using Dynamic Covalent Cross-Linking of Poly(vinyl alcohol)-Heparin Hydrogels for Controlled Cell and Growth Factor Delivery

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• 作者：Justine J. Roberts ; Pratibha Naudiyal ; Lauriane Jugé ; Lynne E. Bilston ; Anthony M. Granville ; Penny J. Martens
• 刊名：ACS Biomaterials Science & Engineering
• 出版年：2015
• 出版时间：December 14, 2015
• 年：2015
• 卷：1
• 期：12
• 页码：1267-1277
• 全文大小：548K
• ISSN：2373-9878

文摘

Heparin-based hydrogels are attractive for cell encapsulation and drug delivery because of the ability of heparin to bind native proteins. However, heparin-based hydrogels have received little attention for their potential as stimuli-sensitive materials. Biosynthetic, poly(vinyl alcohol) (PVA)-heparin hydrogels were formed using dynamic, covalent cross-linking. Hydrogel stimuli-sensitivity was tailored by tuning the concentration of heparin to PVA. Relatively thermally and pH stable hydrogels were produced when formed from only the synthetic, nonionic PVA polymer cross-linked via hydrazone bonds. Cross-linking in the ionic biopolymer heparin, to form PVA-heparin gels, has a profound impact on thermal stability, with degradation ranging from over 6 months to only 4 days across 25–50 °C. PVA-heparin hydrogels degrade within 18 days at basic pH (10), while not fully degrading over 6 months at lower pH (4, 7.4). This finding is attributed to the anionic repulsion of carboxyls and sulfates in heparin. PVA-heparin macromers were cytocompatible and enabled mild cell encapsulation, in addition to providing pH-controlled growth factor release. Overall, it is demonstrated that the biopolymer heparin can be used to create pH and temperature-responsive hydrogel biomaterials for cell and drug delivery.