文献：Extracellular Vesicle Crosslinkers Constructing Hydrogels with Stress-Relaxation and Bioactive Protein Modification

作者：Shi, Yanzhen Jing, Haowen Lu, Fanxuan Zhao, Mengying An, Shuiling Jin, Chang Gao, Yongdong Dai, Yinxin Zhu, Shuxu Yang, Songying Zhang, Xuesong Ye, Xiujun Cai, Yifan Wang

文献链接：https://advanced.onlinelibrary.wiley.com/doi/full/10.1002/admi.202400885

To evaluate the biological functionality of proteins loaded onto EV crosslinkers, we used VEGF as an example protein and encapsulated human umbilical vein endothelial cells (HUVECs) within SH-EV-VEGF crosslinked hydrogels (Figure 4g). After five days of culture, while HUVECs remained rounded and isolated within hydrogels crosslinked with 8-arm PEG-SH, the cells in EV-crosslinked hydrogels began to cluster, demonstrating that the stress relaxation properties of the EV-crosslinked hydrogels allowed cell movement and clustering (Figure 4h–j). Notably, the cell clusters were more prominent within SH-EV-VEGF crosslinked hydrogels. Interestingly, we observed a few instances of sprouting from the cell clusters in SH-EV-VEGF crosslinked hydrogels, indicating a trend toward angiogenesis (Figure 4h–j). In some cases, the sprouting almost connected two separate clusters, verifying that proteins loaded onto EV crosslinkers can maintain their biological function and influence the behavior of encapsulated cells.

为了评估加载到EV交联剂上的蛋白质的生物功能，我们使用VEGF作为示例蛋白质，并将人脐静脉内皮细胞（HUVEC）包裹在SH-EV-VEGF交联水凝胶中。

经过五天的培养，当HUVEC在与8臂PEG-SH交联的水凝胶中保持圆形和分离时，EV交联水凝胶中的细胞开始聚集，表明EV交联水凝胶的应力松弛特性允许细胞移动和聚集。值得注意的是，SH-EV-EGF交联水凝胶中的细胞簇更为突出。

我们观察到SH-EV-EGF交联水凝胶中的细胞簇出现了一些发芽现象，表明有血管生成的趋势。在某些情况下，发芽几乎连接了两个单独的簇，验证了加载到EV交联剂上的蛋白质可以保持其生物功能并影响包封细胞的行为。

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