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    Efficient fabrication of stretching hydrogels with programmable strain gradients as cell sheet delivery vehicles

    Year: 2021

    Journal: Mater. Sci. Eng. C-Mater. Biol. Appl., Volume 129, OCT

    Authors: Huang, Rong; Xu, Lirong; Wang, Yan; Zhang, Yuheng; Lin, Bin; Lin, Zhixiao; Li, Jinqing; Li, Xueyong

    Organizations: Key Industrial Innovation Chain Project and General Project of Shaanxi Provincial Key Research and Development Plan Projec [2020ZDLSF04-13, 2021SF-292]; Discipline Promotion Program [2020XKPT013]; Second Affiliated Hospital of Air Force Medical University [2018JSYJ001]

    Keywords: Gelatin; beta-Cyclodextrin; Programmable mechanical stretch; Cell sheet detachment; Yes-associated protein 1

    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 (beta-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-beta-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.
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