iMASSAGE – in vivo EV production and in situ microbiota modulation

In our gut, the balance of microbial inhabitants plays a crucial role in maintaining our health. However, when pathogenic gut microbiota wreak havoc, it can lead to debilitating gastrointestinal diseases. While our immune system produces extracellular vesicles to combat these harmful microbes, the doses and exposure times are often inadequate.

But what if we could boost the production of these therapeutic extracellular vesicles on demand? A groundbreaking study by researchers at Nanjing University has unveiled a remarkable solution: the iMASSAGE system. This innovative bioelectronic controller, coupled with mechanical stimulation of hydrogel-embedded macrophages, has the power to amplify the production of therapeutic extracellular vesicles by up to 20 times.

The concept is simple yet revolutionary. By leveraging wireless electronics and responsive hydrogel technology, the iMASSAGE system delivers precise mechanical forces to macrophages, prompting them to release a surge of extracellular vesicles. These vesicles act as molecular messengers, effectively neutralizing the deleterious effects of pathogenic gut microbiota and alleviating conditions such as colitis.

iMASSAGE for in vivo EV production and in situ microbiota modulation

Fig. 1

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).

What sets the iMASSAGE system apart is its in vivo controllability. Researchers can fine-tune the production of extracellular vesicles in real time, ensuring optimal therapeutic outcomes. This level of precision opens doors to a wide range of potential applications beyond gastrointestinal diseases, offering hope for the treatment of various other conditions.

Imagine a future where chronic diseases are managed with the push of a button, where patients regain control over their health through cutting-edge bioelectronics. The iMASSAGE system represents a paradigm shift in disease treatment, merging the fields of biology and technology to unlock new possibilities for personalized medicine.

As research continues to unveil the full potential of this groundbreaking technology, we stand on the brink of a new era in healthcare—one where mechanical stimulation and extracellular vesicles pave the way to a healthier, happier future for all.

Wan S, Wang K, Huang P, Guo X, Liu W, Li Y, Zhang J, Li Z, Song J, Yang W, Zhang X, Ding X, Leong DT, Wang L. (2024) Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation. Nat Commun 15(1):3343. [article]

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