Injectable hyaluronic acid/PEG-p(HPMAm-lac)-based hydrogels dually cross-linked by thermal gelling and Michael addition

Injectable hyaluronic acid/PEG-p(HPMAm-lac)-based hydrogels dually cross-linked by thermal gelling and Michael addition
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DOI:
10.1016/j.eurpolymj.2015.07.036
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发表时间:
2015-11-01
影响因子:
6
通讯作者:
Di Martino, Piera
Di Martino, Piera
中科院分区:
化学2区
文献类型:
--
作者:
Dubbini, Alessandra;Censi, Roberta;Di Martino, Piera

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通过基于37 ℃热凝胶化和乙烯砜与巯基之间的同时Michael加成交联的双重交联策略,制备了由乙烯砜-p(HPMAm-lac(1 - 2))-PEG-p(HPMAm-lac(1 -2))三嵌段共聚物和巯基修饰的透明质酸组成的快速原位形成的温敏水凝胶。通过控制乙烯基砜衍生化程度、三嵌段共聚物浓度和硫醇化程度,在9-60分钟的时间内改变化学网络的形成。多糖透明质酸链上的巯基取代程度显著影响所得网络的物理和机械性质,以及溶胀和降解行为,如流变学、吸水实验和降解实验所证实的。此外,所开发的水凝胶在21天的时间范围内对小鼠骨髓基质细胞和NIH 3 T3小鼠成纤维细胞均显示出良好的体外细胞相容性。所开发的水凝胶显示出作为具有可调凝胶化动力学、可调机械性能、溶胀和降解时间的有前途的可注射生物材料的潜力。这些生物材料可以作为再生细胞基质和可控药物输送系统。(C)2015爱思唯尔有限公司版权所有。
Fast in situ forming thermosensitive hydrogels consisted of vinyl sulfone bearing p(HPMAm-lac(1-2))-PEG-p(HPMAm-lac(1-2)) triblock copolymers and thiol modified hyaluronic acid were prepared via a dual cross-linking strategy based on thermal gelation at 37 degrees C and simultaneous Michael addition cross-linking between vinyl sulfone and thiol moieties. The formation of a chemical network was varied within a time period of 9-60 min by controlling the degree of vinyl sulfone derivatization, the triblock copolymer concentration and the degree of thiolation. The extent of thiol substitution on the polysaccharidic hyaluronan chain markedly affected the physical and mechanical properties, as well as the swelling and degradation behavior of the resulting networks, as confirmed by rheology, water uptake experiments And degradation tests. In addition, the developed hydrogels showed a good cytocompatibility in vitro during a timeframe of 21 days both for mouse bone marrow stromal cell and for NIH 3T3 mouse fibroblasts. The developed hydrogels showed potential as promising injectable biomaterials with tunable gelation kinetics, adjustable mechanical properties, swelling and degradation times. These biomaterials could find application both as a regenerative cell matrix and as controlled drug delivery system. (C) 2015 Elsevier Ltd. All rights reserved.