Photopatterning the Mechanical Properties of Polysaccharide-Containing Gels Using Fe3+ coordination
Photopatterning the Mechanical Properties of Polysaccharide-Containing Gels Using Fe3+ coordination
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DOI：
10.1021/acs.chemmater.5b01727
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发表时间：
2015-07-28
影响因子：
8.6
通讯作者：
Ostrowski, Alexis D.
中科院分区：
文献类型：
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作者：
Giammanco, Giuseppe E.;Ostrowski, Alexis D.
基质材料是组织工程中必不可少的元素，支撑基质的化学和物理性质可以最终控制生长细胞的命运和活力。1 - 4用于再生医学的生物材料需要提供简单的方法来修改和调整这些特性，以便控制基底材料与生长组织的相互作用。大多数用于组织工程和细胞培养的材料具有均匀的力学性能。然而，在体内，细胞可能发现不同组织界面的细胞外基质刚度的动态变化或作为疾病状态的结果。5,6基质材料的弹性为生长细胞的发育创造了机械线索。1,5,7使用模型系统（如聚丙烯酰胺（Paam）凝胶）对这些信号进行了广泛的研究，其中刚度可以通过在配方1,8−10期间调整试剂的比例来控制，或者使用不同强度的光或热对底物进行不均匀或多步聚合。1,3,5,10,11然而，这些方法都没有提供一种合成后的替代方法来调节和控制基板的机械性能。我们描述了一种简单的方法，用于已经制备的水凝胶材料的光图图化，以创建刚度和弹性的梯度和界面。通过这些材料的图案，我们可以创造机械线索来控制和指导细胞的发育。混合Paam -多糖材料已被报道，并被描述为高拉伸性，12,13金属离子响应，14和良好的絮凝剂。这些材料被证明具有生物相容性和无细胞毒性，在药物输送系统16和组织工程材料中具有成熟的应用。17,18我们的方法是将含尿醛酸多糖（UCPS）引入聚丙烯酰胺凝胶中，以产生混合水凝胶网络。我们使用了三种不同的UCPS：海藻酸盐（Alg）、果胶酸盐（Pec）和透明质酸盐（Hya）。这些天然多糖在其结构中存在羧酸基团（支持信息图S1）。羧酸基板与过渡金属（如铁）的相互作用之前已被用于制造对不同刺激作出反应的材料，以经历结构和机械变化。19−23据描述，在Fe （III）存在下，聚脲酸盐海藻酸盐和果胶酸盐形成光反应性水凝胶，其中紫外线和可见光照射可以通过触发金属的还原和多糖的脱羧来诱导凝胶的物理状态发生变化（支持信息方案S1）。22,24,25在这项工作中，我们首次提出了Fe (III) -透明质酸盐作为光响应系统，表现出与Alg和Pec相似的行为。这些系统的光化学操作允许paam基凝胶在可见光照射下发生机械变化（图1）。此外，多糖羧酸基团分布的变化在与金属的配位中产生了不同的动态。在开始聚合之前，将UCPS加入丙烯酰胺溶液中，可以很容易地制备混合凝胶（支持信息图S2）。在该反应中，丙烯酰胺的聚合不仅由APS/TEMED体系引发，而且由多糖链上形成的烷氧基自由基引发。26,27接枝反应和添加的MBA都有助于材料的共价交联，而多糖中的羧酸盐提供了与金属产生非共价动态相互作用的机会。14
Substrate materials are an essential element in tissue engineering, where the chemical and physical properties of the support matrix can ultimately control the fate and viability of the growing cells. 1− 4 Biomaterials for applications in regenerative medicine need to offer easy ways to modify and tune these properties in order to control the interactions of the substrate material with the growing tissue. Most materials used for tissue engineering and cell culture present uniform mechanical properties. However, in vivo, cells may find dynamic changes in the stiffness of the extracellular matrix at the interface of different tissues or as a consequence of disease states. 5, 6 The elasticity of substrate materials creates mechanical cues for the development of the growing cells. 1, 5, 7 These cues have been widely studied using model systems such as polyacrylamide (Paam) gels, where the stiffness can be controlled by adjusting the ratio of reagents during the formulation 1, 8− 10 or performing uneven or multistep polymerization of the substrate with different intensities of light or heat. 1, 3, 5, 10, 11 However, none of these approaches offers a postsynthetic alternative for tuning and controlling the mechanical properties of the substrate. We describe a facile method for the photopatterning of already prepared hydrogel materials to create gradients and interfaces in stiffness and elasticity. By patterning these materials, we could create mechanical cues to control and direct the development cells. Mixed Paam− polysaccharide materials have been reported and are described as highly stretchable, 12, 13 metal− ion responsive, 14 and good flocculants. 15 These materials were shown to be biocompatible and noncytotoxic, with proven applications in drug delivery systems, 16 and as materials for tissue engineering. 17, 18 Our approach is to introduce uronatecontaining polysaccharides (UCPS) into polyacrylamide gels, to produce mixed hydrogel networks. We used three different UCPS: alginate (Alg), pectate (Pec), and hyaluronate (Hya). These natural polysaccharides present carboxylate groups in their structure (Supporting Information Figure S1). The interaction of carboxylate-bearing substrates with transition metals such as iron has been used before to create materials that respond to different stimuli to undergo structural and mechanical changes. 19− 23 Polyuronates alginate and pectate have been described to form photoresponsive hydrogels in the presence of Fe (III), where illumination with UV and visible light can induce changes in the physical state of the gel by triggering the reduction of the metal and the decarboxylation of the polysaccharide (Supporting Information Scheme S1). 22, 24, 25 In this work, we present for the first time Fe (III)− hyaluronate as a photoresponsive system, showing a similar behavior to Alg and Pec. The photochemical manipulation of these systems allows for mechanical changes in the Paam-based gels upon visible light irradiation (Figure 1). Furthermore, changes in the distribution of the polysaccharide carboxylate groups create a different dynamic in the coordination with metals.The mixed gels were easily prepared by incorporating the UCPS into the acrylamide solution before initiating the polymerization (Supporting Information Figure S2). In this reaction, the acrylamide polymerization is initiated not only by the APS/TEMED system but also by alkoxy radicals formed on the polysaccharide chain. 26, 27 Both the grafting reaction and the added MBA contribute to covalent cross-linking of the material, while the carboxylates in the polysaccharide offer the opportunity to create noncovalent dynamic interactions with metals. 14