Fabricating functional cell sheets with excellent mechanical strength for tissue regeneration remains challenging. Therefore, we devised a novel 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide/N-hydroxy-succinimide crosslinked hydrogel carrier composed of gelatin (Ge) and beta-cyclodextrin (β-CD) that promoted the adhesion and proliferation of keratinocytes (Kcs) compared with those cultured on a Ge hydrogel due to significantly higher pore size, porosity, and stiffness, as confirmed using field emission scanning electron microscopy (FE-SEM) and shear wave elastography (SWE). Upon exposure to a programmable gradient microenvironment, cells displayed a stress/strain-dependent spatial-temporal distribution of extended cellular phenotypes and cytoskeletons. The promoted proliferation of Kcs and the increased retention of the undifferentiated cell phenotype on Ge-β-CD composite hydrogels under a 15% strain led to the accelerated detachment of cell sheets with retained cell-cell junctions. Moreover, the stretch-triggered upregulated expression of phosphorylated yes-associated protein (YAP) 1 suggested that this effect might be associated with the mechanical stimulation-induced activation of the YAP pathway.

制造具有出色机械强度用于组织再生的功能性细胞片仍然具有挑战性。因此，我们设计了一种由明胶 (Ge) 和 β-环糊精 (β-CD) 组成的新型 1-乙基-3-(3-二甲基氨基丙基) 碳二亚胺/N-羟基-琥珀酰亚胺交联水凝胶载体，可促进其粘附和增殖。使用场发射扫描电子显微镜 (FE-SEM) 和剪切波弹性成像 (SWE) 证实，角质形成细胞 (Kcs) 与在 Ge 水凝胶上培养的细胞相比，由于显着更高的孔径、孔隙率和刚度。在暴露于可编程梯度微环境后，细胞显示出扩展的细胞表型和细胞骨架的应力/应变依赖性时空分布。在 15% 的应变下，Kcs 的促进增殖和未分化细胞表型在 Ge-β-CD 复合水凝胶上的保留增加，导致细胞片与保留的细胞 - 细胞连接加速分离。此外，牵张触发的磷酸化 yes 相关蛋白 (YAP) 1 的表达上调表明这种效应可能与机械刺激诱导的 YAP 通路激活有关。