The endothelial cell (EC) outgrowth in both vasculogenesis and angiogenesis starts with remodeling surrounding matrix and proceeds with the crosstalk between cells for the multicellular vasculature formation. The mechanical plasticity of matrix, defined as the ability to permanently deform by external traction, is pivotal in modulating cell behaviors. Nevertheless, the implications of matrix plasticity on cell-to-cell interactions during EC outgrowth, along with the molecular pathways involved, remain elusive. Here we develop a collagen-hyaluronic acid based hydrogel platform with tunable plasticity by using compositing strategy of dynamic and covalent networks. We show that although the increasing plasticity of the hydrogel facilitates the matrix remodeling by ECs, the largest tubular lumens and the longest invading distance unexpectedly appear in hydrogels with medium plasticity instead of the highest ones. We unravel that the high plasticity of the hydrogels promotes stable integrin cluster of ECs and recruitment of focal adhesion kinase with an overenhanced contractility which downregulates the vascular endothelial cadherin expression and destabilizes the adherens junctions between individual ECs. Our results, further validated with mathematical simulations and in vivo angiogenic tests, demonstrate that a balance of matrix plasticity facilitates both cell-matrix binding and cell-to-cell adherens, for promoting vascular assembly and invasion.
Dye-containing wastewater is one of the major issues in water contamination, and its treatment remains a serious problem due to the low concentrations of dyes in polluted natural water and high cost for purification. Herein, we report the application of graphene oxides (GO) in the decontamination of ppm levels of methylene blue (MB) in an aqueous solution. During the dye removal process, GO adsorbs MB molecules via strong interactions including π–π stacking and electrostatic attraction, and facilitates the precipitation of GO/MB complexes, which can be readily removed from the solution. The adsorption progress follows the Langmuir isotherm model and the pseudo-second-order kinetic model. The thermodynamic parameters indicate that the adsorption progress is a spontaneous progress. By using our strategy, a dye removal rate as high as 95% has been achieved with a final dye concentration of only 0.25 ppm. In addition, 82% of the dye can be recycled through ethanol extraction from the collected GO/MB complexes. All the results demonstrate that GO nanosheets can effectively remove and recover ppm levels of cationic dye pollutants, represented by MB, showing the promising application of GO in ultra-low concentration dye containing wastewater treatment.
Exosomes, which are nanoscale vesicles secreted by almost all cell types via paracrine pathways, play a crucial role in intercellular communication. For nearly a decade, exosomes have been widely exploited to develop novel biologic therapeutic strategies for recalcitrant clinical problems such as chronic wounds. Due to the excellent biocompatibility and immune stability of exosomes, exosome-based therapy has shown greater potential for chronic wound healing than other biotherapies (e.g., transplantation of stem cells) and holds great promise for the clinical treatment of chronic wounds. Here, recent advances in regulating the features and biological functions of cell-derived exosomes by biochemical and biophysical cues in the cell microenvironment are systematically summarized. Subsequently, microenvironmental cue-regulated exosomes as therapeutic strategies to improve chronic wound healing by regulating the inflammatory response, promoting cell proliferation and migration, facilitating angiogenesis, and regulating extracellular matrix (ECM) remodeling are discussed, and hydrogel-based exosome delivery systems used in the treatment of chronic wounds are highlighted. Finally, ongoing challenges and future opportunities in this rapidly developing field are proposed.