Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels
Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels
复制标题
肿胀介导的机械刺激调节脂肪来源的间充质干细胞的分化，用于使用可注射 UCST 微凝胶修复椎间盘
DOI：
10.1002/adhm.202201925
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发表时间：
2022-10-31
影响因子：
10
通讯作者：
Chen, Qixin
中科院分区：
文献类型：
--
作者：
Huang, Xianpeng;Chen, Di;Chen, Qixin
机械刺激是组织工程中控制干细胞分化的有效方法。然而，其在体内组织修复中的实现仍然具有挑战性，因为这种类型的刺激几乎不能应用于可注射的接种系统。在这里，它提出了可注射微凝胶的溶胀可以通过拉伸粘附在其表面上的细胞转化为原位机械刺激。采用反相乳液聚合法制备了具有上临界溶解温度特性的聚丙烯酰胺-共-丙烯酸微凝胶，并进一步用聚多巴胺包覆以增加细胞粘附。粘附在微凝胶上的脂肪间充质干细胞（ADSCs）可随着微凝胶的响应性溶胀而沿着被全方位拉伸，上调TRPV 4和Piezo 1通道蛋白，促进ADSCs向髓核（NP）样分化。体内实验表明，植入微凝胶后，NP的椎间盘高度和细胞外基质含量增加。研究结果表明，在椎间盘修复过程中，肿胀诱导的机械刺激具有调节干细胞分化的巨大潜力。
Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface. Poly(acrylamide‐co‐acrylic acid) microgels with the upper critical solution temperature property are fabricated using inverse emulsion polymerization and further coated with polydopamine to increase cell adhesion. Adipose‐derived mesenchymal stem cells (ADSCs) adhered on the microgels can be omnidirectionally stretched along with the responsive swelling of the microgels, which upregulate TRPV4 and Piezo1 channel proteins and enhance nucleus pulposus (NP)‐like differentiation of ADSCs. In vivo experiments reveal that the disc height and extracellular matrix content of NP are promoted after the implantation with the microgels. The findings indicate that swelling‐induced mechanical stimulation has great potential for regulating stem cell differentiation during intervertebral disc repair.