Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems
Production of heparin-functionalized hydrogels for the development of responsive and controlled growth factor delivery systems
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DOI：
10.1016/j.jconrel.2007.04.019
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发表时间：
2007-10-08
影响因子：
10.8
通讯作者：
Kiick, Kristi L.
中科院分区：
文献类型：
--
作者：
Nie, Ting;Baldwin, Aaron;Kiick, Kristi L.
我们和其他人之前已经证明了基于非共价蛋白质-糖胺聚糖相互作用组装聚合水凝胶的方法，并有望开发受体响应性水凝胶材料；此类系统机械性能的改进将扩大其用途。因此，原位可交联和可降解的含肝素水凝胶被设计用于生长因子的结合和控制释放。具体来说，马来酰亚胺官能化高分子量肝素（HMWH）是通过简单的化学方法合成的，通过控制催化剂和反应条件，可以通过控制催化剂和反应条件，用马来酰亚胺基团轻松、可控地修饰 HMWH 中的羧酸盐，并通过 H-1 NMR 光谱进行评估。这些修饰的肝素通过与各种硫醇官能化 PEG 反应交联成水凝胶。通过振荡流变测定法评估的凝胶的胶凝时间和弹性模量可以通过控制 HMWH 的功能、水凝胶的浓度、基于 PEG 的交联剂的特性以及马来酰亚胺和硫醇基团之间的摩尔比来调节。通过免疫化学测定研究了水凝胶与生长因子结合的能力。初步研究表明这些材料可控制释放碱性成纤维细胞生长因子（bFGF），并表明它们在响应性材料的设计中具有更广泛的用途。 (c) 2007 Elsevier B.V 保留所有权利。
Methods to assemble polymeric hydrogels on the basis of noncovalent protein-glycosaminoglycan interactions have been previously demonstrated by us and others and hold promise in the development of receptor-responsive hydrogel materials; improvements in the mechanical properties of such systems would broaden their utility. Thus, in situ crosslinkable and degradable heparin-containing hydrogels were designed for the binding and controlled release of growth factors. Specifically, maleimide-functionalized high molecular weight heparin (HMWH) was synthesized via straightforward chemical methods that permitted facile and controllable modification of carboxylates in HMWH with maleimide groups via control of catalyst and reaction conditions, as assessed via H-1 NMR spectroscopy. These modified heparins were crosslinked into hydrogels via reaction with various thiol-functionalized PEGs. The gelation times and elastic moduli of the gels, as assessed through oscillatory rheometry, could be tuned by controlling the functionality of HMWH, the concentration of the hydrogel, the identity of the PEG-based crosslinker, as well as the molar ratio between maleimide and thiol groups. The capability of the hydrogels to bind to growth factors was investigated with immunochemical assays. Preliminary studies indicate the controlled release of basic fibroblast growth factor (bFGF) from these materials and suggest their broader use in the design of responsive materials. (c) 2007 Elsevier B.V All rights reserved.