The preparation and biocompatible evaluation of injectable dual crosslinking hyaluronic acid hydrogels as cytoprotective agents
The preparation and biocompatible evaluation of injectable dual crosslinking hyaluronic acid hydrogels as cytoprotective agents
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可注射双交联透明质酸水凝胶细胞保护剂的制备及生物相容性评价
DOI：
10.1039/c9tb00839j
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发表时间：
2019-07-28
影响因子：
7
通讯作者：
Zhang, Xingdong
中科院分区：
文献类型：
--
作者：
Cao, Wanxu;Sui, Junhui;Zhang, Xingdong
可注射水凝胶由于其在体内原位形成而吸引了大量关注，与传统水凝胶支架相比，其最大限度地降低了外科手术期间的重大创伤风险。点击化学广泛用于制备可注射水凝胶，尽管其中一些需要光引发剂或催化剂，其可能具有细胞毒性并损害包封细胞的增殖。在本研究中，通过巯基-烯点击反应和巯基与二硫键在中性pH下的转化，设计了可注射的双交联水凝胶。巯基和丙烯酸酯基团成功地接枝到HA上，并使用FT-IR和H-1-NMR进行表征。水凝胶的凝胶化时间、形态、注射力、溶胀、降解、力学性能和药物释放行为随水凝胶的分子量（M-w = 0.1，1.0，2.0 MDa）而变化。MTT、FDA/PI染色和扫描电镜（SEM）显示，包封的L929在不同分子量的水凝胶中增殖良好。还观察到，在低分子量（0.1MDa）水凝胶系统中，细胞更好地分布并且分泌更多的细胞外基质。小鼠皮下注射也证明水凝胶可以支持包封的L929细胞在体内的增殖，并且没有观察到外周细胞向材料内部的显著浸润。这些结果表明，这种可注射的透明质酸基水凝胶是一种优良的细胞保护剂，并表现出良好的生物相容性，具有生物医学应用的潜力，如细胞输送和术后抗粘连。
Injectable hydrogels attract a great deal of attention due to their in situ formation in vivo, which minimizes the risk of major trauma during the surgical procedure as compared to traditional hydrogel scaffolds. Click chemistry is widely used in the preparation of injectable hydrogels, although some of them require photoinitiators or catalysts that may be cytotoxic and impair the proliferation of encapsulated cells. In the present study, an injectable dual crosslinking hydrogel was designed by a thiol-ene click reaction and conversion between sulfhydryl and disulfide bonds at a neutral pH. The sulfhydryl group and acrylate group were successfully grafted onto HA and characterized using FT-IR and H-1-NMR. The gelation time, morphology, injection force, swelling, degradation, mechanical properties and drug release behavior of the hydrogel varied with the molecular weight of the hydrogel (M-w = 0.1, 1.0, 2.0 MDa). MTT, FDA/PI staining and scanning electron microscopy (SEM) showed that the encapsulated L929 proliferated well in different molecular weight hydrogels. It was also observed that in a low molecular weight (0.1 MDa) hydrogel system, the cells were better distributed and secreted more extracellular matrix. Subcutaneous injection in mice also demonstrated that hydrogels could support the proliferation of encapsulated L929 cells in vivo, and no significant infiltration of peripheral cells into the interior of the material was observed. These results indicate that this injectable hyaluronan-based hydrogel is an excellent cell protectant and exhibits good biocompatibility, with potential for biomedical applications such as cell delivery and postoperative anti-adhesion.