Fig. 1: iMASSAGE for in vivo EV production and in situ microbiota modulation.

a Schematics of the biogenesis of EVs and host EVs bridged cross-species communication between host cell and microbiome in vivo. EVs carrying abundant cellular bioactive substances modulating microbiota. Photo credit: Xianguang Ding. b Schematic illustration of the implantable iMASSAGE device. Insert shows the iMASSAGE device size. Scale bar, 3 mm. Photo credit: Xianguang Ding. c Scanning electron microscopy (SEM) image of cells resided in iMASSAGE device. The white arrows indicate the loaded cells on hydrogel. Scale bar: 20 μm. d Left, schematic of embedded cells under iMASSAGE treatment, in relaxed and contracted states. Photo credit: Kepeng Wang. Right, computed distributions of strain on embedded cells at the top and sectional view after iMASSAGE, assuming an ellipsoidal shape cell adheres on the hydrogel surface. e Left, representative fluorescence images of cell immunostained for CD63 after normally cultured (static) and iMASSAGE treated. Scale bar, 2 μm. Right, compared to commonly used static cell culture conditions, iMASSAGE treatment promotes EV biogenesis. f Top, schematic illustrations showing the placement of iMASSAGE on the mesentery. Photo credit: JingJing Zhang. Down, a representative image of a freely behaving mice implanted with iMASSAGE device. The white light emitted on the implantation verified function (indicated by a red arrow).