Peripheral nerves connect the brain and spinal cord to muscles, organs, and sensory systems, making them key targets for treating neurological and systemic diseases. However, implantable bioelectronic devices placed on these nerves often trigger the body’s immune response. This leads to fibrotic scar tissue forming around the device, which disrupts electrical signaling, reduces therapeutic effectiveness, and limits how long implants can function reliably.

This immune-driven scarring has been a major barrier to long-term neuromodulation therapies, including those aimed at treating chronic conditions such as hypertension. Researchers have now demonstrated that preventing fibrosis at the nerve–device interface is possible, enabling stable, long-term nerve stimulation and sustained therapeutic effects without relying on drugs.

A research team at the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA) has developed a robust bioadhesive strategy that firmly attaches bioelectronic devices directly to peripheral nerves, creating stable interfaces that the immune system does not wall off with fibrotic tissue. The approach was designed to work across diverse peripheral nerves rather than being limited to a single anatomical site.

By adhering the bioelectrodes to the nerve surface, the interface blocks immune cell infiltration that normally occurs when devices are loosely attached or simply wrapped around nerves. This prevents the inflammatory cascade that leads to fibrous capsule formation, while still allowing continuous electrical stimulation of the targeted nerve over extended periods.

The strategy was tested in preclinical rodent models on multiple peripheral nerves, including the occipital, vagus, sciatic, tibial, common peroneal, and deep peroneal nerves. Devices were implanted and used for continuous nerve stimulation for up to 12 weeks, allowing the researchers to assess both immune response and functional stability over time.

The results, published in Science Advances, showed minimal macrophage activity and very limited deposition of collagen and smooth muscle actin at the adhesive interfaces. Compared with non-adhered control devices, the adhesive implants remained largely free of fibrosis and maintained stable neuromodulation performance throughout the study period.

Using this non-fibrotic interface, the researchers demonstrated long-term, drug-free blood pressure regulation by stimulating the deep peroneal nerve, a site historically associated with acupuncture-based hypertension treatment. Blood pressure control was maintained for weeks without the side effects commonly seen with vagus or carotid sinus nerve stimulation.

The findings suggest that adhesive, non-fibrotic bioelectronic interfaces could significantly expand the clinical potential of implantable neuromodulation devices. The team plans to further develop the platform for broader translational applications, including chronic cardiovascular, neurological, and metabolic conditions where long-term nerve stimulation is required.

“The contrast between the immune response of the adhered device and that of the non-adhered control is striking,” said Bastien Aymon, a study co-author and a PhD candidate in mechanical engineering. “The fact that we can observe immunologically pristine interfaces after three months of adhesive implantation is extremely encouraging for future clinical translation.”

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