Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions
Rationally designed protein cross-linked hydrogel for bone regeneration via synergistic release of magnesium and zinc ions
复制标题
合理设计的蛋白质交联水凝胶通过协同释放镁和锌离子实现骨再生
DOI：
10.1016/j.biomaterials.2021.120895
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发表时间：
2021-05-18
期刊：
影响因子：
14
通讯作者：
Peng, Songlin
中科院分区：
文献类型：
--
作者：
Chen, Xin;Tan, Baoyu;Peng, Songlin
开发具有良好机械强度和有效载药能力的重组蛋白交联可注射水凝胶用于骨再生是非常有吸引力的，但很少报道。在这里，我们报告了一个智能水凝胶传递系统的制造，将合理设计的T4溶菌酶突变体（T4 M）介导的局部交付和协同释放的Mg 2+和Zn 2+骨修复。除了其固有的抗菌特性之外，T4 M在其表面上具有丰富的游离胺基，以用作有效的共价交联剂来加强水凝胶网络，并对多价阳离子如Zn 2+表现出特异性结合亲和力。此外，整合素受体结合Arg-Gly-Asp（RGD）序列被引入到T4溶菌酶的C-末端，以提高其细胞亲和力，进一步促进快速组织再生。最终的复合水凝胶显示出优异的可注射性、改善的机械性能、抗菌活性和独特的生物活性。在水凝胶中有效负载Mg 2 +/Zn 2+可以介导Mg 2+和Zn 2+的顺序和持续释放，从而通过调节MAPK信号通路而导致协同增强骨再生。我们相信，本文提出的策略为开发用于组织再生的蛋白质交联智能递送系统开辟了一条新的途径。
The development of recombinant protein cross-linked injectable hydrogels with good mechanical strength and effective drug loading capacity for bone regeneration is extremely attractive and rarely reported. Here, we report the fabrication of a smart hydrogel delivery system by incorporating a rationally designed T4 lysozyme mutant (T4M) to mediate the localized delivery and synergistic release of Mg2+ and Zn2+ for bone repair. Apart from its intrinsic antibacterial properties, T4M bears abundant free amine groups on its surface to function as effective covalent crosslinkers to strengthen the hydrogel network as well as exhibits specific binding affinity to multivalent cations such as Zn2+. Moreover, the integrin receptor-binding Arg-Gly-Asp (RGD) sequence was introduced onto the C-terminus of T4 lysozyme to improve its cellular affinity and further facilitate rapid tissue regeneration. The final composite hydrogel displays excellent injectability, improved mechanical properties, antibacterial activity, and unique bioactivities. The effective loading of Mg2+/Zn2+ in the hydrogels could mediate the sequential and sustained release of Mg2+ and Zn2+, thereby resulting in synergistic enhancement on bone regeneration through modulation of the MAPK signaling pathway. We believe that the strategy proposed in this paper opens up a new route for developing protein cross-linked smart delivery systems for tissue regeneration.