What inspired the research?
“Our main motivation came from the clinical reality: hypertension remains a leading risk factor for cardiovascular disease, yet the current standard of care – daily oral medication – often suffers from poor adherence and delayed response. We wanted to explore whether a closed-loop bioelectronic system could intervene in real time, delivering therapy exactly when blood pressure rises. At the same time, advances in microneedle engineering and electrocatalysis gave us the opportunity to integrate sensing and therapy in one wearable device. So, the driving force was really both the unmet medical need and the unique chance to combine diagnostics and therapeutics into a single platform.”
What was the biggest challenge?
“One of the hardest problems was achieving selective, safe, and efficient generation of nitric oxide inside the body. Electrochemical systems usually generate many reactive intermediates, so we had to carefully design a cascade system – gold nanoparticles for oxygen reduction, copper–nitrogen nanoribbons for NO production, and platinum nanoparticles to scavenge by-products. Another challenge was ensuring that the NO actually reached blood vessels, since diffusion through skin is normally very limited. That’s why we introduced electroosmotic flow, which extended penetration depth to about 4 mm. On the sensing side, building a reliable cuff-less blood pressure monitor based on photoplethysmography required extensive signal processing and validation. Each of these elements – catalysis, microneedle mechanics, electronics, and sensing – had to be optimized and then stitched together.”
Did the results surprise you?
“Yes, two points stood out in particular. First, the effect of electroosmotic flow surprised us – it expanded the diffusion area of nitric oxide by several times. Second, in pig model testing, the systemic blood pressure reduction induced by the patch convinced us that localized intervention targeting skin microvessels may yield systemic therapeutic benefits.”
Under the Hood
At the heart of the patch is a microneedle array that painlessly penetrates the outer skin barrier, creating direct conduits for both sensing and therapy. Each microneedle tip is coated with catalytic nanomaterials arranged in a cascade reaction system:
Gold nanoparticles first reduce oxygen.
Copper–nitrogen nanoribbons then selectively generate nitric oxide (NO).
Platinum nanoparticles mop up unwanted by-products, ensuring safety.
This layered design allows for controlled, localized production of NO – a well-known vasodilator – directly under the skin.
A second innovation is the electroosmotic flow mechanism. By applying a gentle electric field, the patch drives NO deeper into tissue, extending penetration to around 4 millimeters, enough to reach dermal microvessels and trigger systemic blood pressure reductions.
For real-time monitoring, the patch integrates a cuffless blood pressure sensor based on photoplethysmography (PPG). Advanced algorithms filter out motion noise and translate optical signals into accurate pressure readings. When the system detects a spike in blood pressure, it automatically activates the catalytic module to release NO, creating a closed-loop feedback cycle.
The entire device is built on a flexible electronic substrate, allowing it to conform to the skin and maintain intimate contact during daily activity.
What role did interdisciplinary collaboration play?
“This project would not have been possible without interdisciplinary teamwork. Our team comprises researchers with backgrounds in chemistry, chemical engineering and technology, materials science and engineering, biomedical engineering, and medical-related fields. We collaborated on developing catalytic nanomaterials, designing microneedles and flexible circuits, and conducting animal studies; furthermore, clinicians provided guidance on medical requirements. The closed-loop nature of the patch required us to constantly align perspectives: how to translate a chemical reaction into a safe therapeutic effect, how to make electronics conform to skin, and how to validate performance in vivo. The most rewarding part was seeing these different pieces click together into a single working system.”
What impact could this patch have?
“Our closed-loop patch is especially valuable for patients with unstable blood pressure – for example, those experiencing rapid fluctuations after surgery or during critical care. In such scenarios, oral drugs are often too slow or imprecise, while our system can respond instantly to blood pressure spikes by releasing nitric oxide on demand. This capacity to stabilize dynamic blood pressure in real time could reduce risks of acute cardiovascular incidents and improve post-operative recovery. Hypertension is just one target. The same principle – real-time sensing plus on-demand drug or gas release – could be extended to other conditions such as arrhythmia, chronic wounds, or even neurological disorders. Ultimately, these devices may shift the paradigm from “take your pill and hope it works” to “let the body and the device co-regulate in real time.”
What’s next?
“Our next steps are threefold: (i) Miniaturization and wearability: we are working on integrating all modules onto a single flexible substrate, making the patch thinner and more comfortable; (ii) Long-term testing: we need to assess durability, skin compatibility, and stability over weeks or months of use; (iii) Towards human studies: our pig model already provides strong translational relevance, but eventually we want to move into carefully designed human trials.
“We are also exploring whether similar microneedle-based closed-loop patches could deliver other therapeutics beyond nitric oxide. Beyond blood pressure, we are also exploring expanding the platform to other therapeutic targets. For example, the same microneedle-based closed-loop design could be adapted to deliver anti-inflammatory agents for chronic wounds, or even neuromodulatory molecules for neurological disorders. In this way, the patch serves as a versatile template for precision medicine.”
Wansong Chen is Associate Pressor of Chemistry and Chemical Engineering at Central South University, Changsha, Hunan 410083, China.
You can access the paper, published in Science Advances, here.
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