Self-Assembled Injectable Nanocomposite Hydrogels Stabilized by Bisphosphonate-Magnesium (Mg2+) Coordination Regulates the Differentiation of Encapsulated Stem Cells via Dual Crosslinking
Self-Assembled Injectable Nanocomposite Hydrogels Stabilized by Bisphosphonate-Magnesium (Mg2+) Coordination Regulates the Differentiation of Encapsulated Stem Cells via Dual Crosslinking
复制标题
双膦酸盐-镁 (Mg2) 配位稳定的自组装可注射纳米复合水凝胶通过双交联调节封装干细胞的分化
DOI：
10.1002/adfm.201701642
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发表时间：
2017
影响因子：
19
通讯作者：
Bian Liming
中科院分区：
文献类型：
--
作者：
Zhang Kunyu;Feng Qian;Xu Jianbin;Xu Xiayi;Tian Feng;Yeung Kelvin W K;Bian Liming
纳米复合水凝胶由嵌入纳米颗粒（NP）的聚合物基质组成，为水凝胶提供了独特的生物活性和机械性能。通过原位沉淀将纳米颗粒掺入聚合物基质中，进一步增强了这些理想的水凝胶性能。然而，这种原位沉淀策略通常需要非细胞相容的pH、渗透压和较长的持续时间，从而阻碍了细胞封装在所得水凝胶中。双膦酸盐 (BP) 表现出多种特定的生物活性以及对镁离子 (Mg2+) 等多价阳离子的优异结合亲和力。在这里，描述了通过双膦酸盐-Mg2+配位驱动的自组装制备纳米复合水凝胶。将带有 BP、BP 单体 (Ac-BP) 和 Mg2+ 的聚合物溶液混合后，这种有效且动态的配位导致 Ac-BP-Mg NP 快速自组装，Ac-BP-Mg NP 充当多价交联剂，在生理 pH 值下稳定所得水凝胶结构。与通过共混预制纳米粒子制备的水凝胶相比，所获得的纳米复合水凝胶具有自修复性，并且表现出改善的机械性能。重要的是，本研究中的水凝胶允许封装细胞并随后注射，而不会影响种子细胞的活力。此外，Ac-BP-Mg NPs 表面上的丙烯酸酯基团能够通过紫外线诱导的二次交联轻松地控制水凝胶的刚度和交联密度，并且发现这种二次交联的延迟引入增强了细胞铺展和成骨。
Nanocomposite hydrogels consist of a polymer matrix embedded with nanoparticles (NPs), which provide the hydrogels with unique bioactivities and mechanical properties. Incorporation of NPs via in situ precipitation in the polymer matrix further enhances these desirable hydrogel properties. However, the noncytocompatible pH, osmolality, and lengthy duration typically required for such in situ precipitation strategies preclude cell encapsulation in the resultant hydrogels. Bisphosphonate (BP) exhibits a variety of specific bioactivities and excellent binding affinity to multivalent cations such as magnesium ions (Mg2+). Here, the preparation of nanocomposite hydrogels via self‐assembly driven by bisphosphonate‐Mg2+coordination is described. Upon mixing solutions of polymer bearing BPs, BP monomer (Ac‐BP), and Mg2+, this effective and dynamic coordination leads to the rapid self‐assembly of Ac‐BP‐Mg NPs which function as multivalent crosslinkers stabilize the resultant hydrogel structure at physiological pH. The obtained nanocomposite hydrogels are self‐healing and exhibit improved mechanical properties compared to hydrogels prepared by blending prefabricated NPs. Importantly, the hydrogels in this study allow the encapsulation of cells and subsequent injection without compromising the viability of seeded cells. Furthermore, the acrylate groups on the surface of Ac‐BP‐Mg NPs enable facile temporal control over the stiffness and crosslinking density of hydrogels via UV‐induced secondary crosslinking, and it is found that the delayed introduction of this secondary crosslinking enhances cell spreading and osteogenesis.