- My PhD research -

The success of implanted medical devices is hindered by an inevitable inflammatory response called the Foreign Body Response (FBR). The human body recognises any implanted material as a foreign object, and isolates it from the rest of the body by producing a thick, hypo-permeable fibrous capsule around it. Fibrous encapsulation can eventually lead to device failure and require its replacement.

Implanted devices such as orthopedic implants (bone replacers, artificial hips), cardiovascular implants (stents, pacemakers), drug and cell delivery platforms (pumps, drug-eluding scaffolds) and biosensors (glucose monitors) are all affected by the FBR, as the fibrous capsule impairs mass transport, drug release, integration and communication with the host tissue. For example, 30-50% of implantable pacemakers and 30% of mammoplasty prosthetics fail due to fibrous encapsulation.

During my PhD, we focused on Diabetes Mellitus and the challenges posed by the FBR when managing it. Diabetes Mellitus is a group of diseases characterised by the inability of the body to regulate glucose metabolism. Approximately 9% of the population worldwide is impacted by it. According to the International Diabetes Federation, 537 million people are currently living with Diabetes, and this figure is expected to rise to 783 million by 2045. Diabetes can take multiple forms and vary in progression, and is therefore classified in various types (type 1, type 2 and gestational).

Type 1 Diabetes Mellitus (T1DM), which accounts for 10% of diabetes cases, is a chronic autoimmune disease in which insulin is not produced in enough quantity to control glucose levels in the body. Insulin is the hormone responsible for the absorption of glucose (sugar) by our cells when eating; however, in T1DM, the cells in the pancreas producing insulin are being destroyed by the immune system. People with T1DM therefore require insulin injections to bring down their sugar levels, as high glucose levels can damage nerves and impact many organs, and eventually lead to various complications such as neuropathy, nephropathy, retinopathy and even death.

People with T1DM use a wide range of devices to manage their condition, such as glucose monitors (to sense how high their sugar levels are), infusion systems (to inject insulin to bring down glucose levels when needed) and management devices (to control the other two and make sure glucose levels remain within a healthy range). In the 70s, continuous insulin infusion pumps started to be developed to replace the painful multiple injections diabetics had to take each day. Those pumps consist of a needle which remains under the skin for a few days and continuously infuses insulin throughout the day, with extra doses delivered following meals.

Continuous insulin infusion pumps have drastically changed how diabetics manage their condition. However, still to this day, those devices need to be replaced every two to three days. This is due to the FBR, which blocks the needle and stops the flow of insulin into the body, leading to device failure and treatment interruption. Those frequent device replacements dramatically affect the patients’ quality of life, as they are both painful and costly. The FBR remains the biggest challenge that implanted drug delivery devices must overcome.

A soft robot, implanted in the body, which can release therapy, adapt to its host and overcome the immune system.

Our project focused on novel technologies to increase the longevity of such implanted devices. First, we developed a sensor that can monitor the fibrous encapsulation of the implant in real-time. By sending small electrical waves in the surrounding tissue, the implant can understand how blocked it has become. Second, we developed a mechanism that can change the force at which insulin is pushed out of the device. By delivering insulin via a “soft” robot, we can change how much force is applied to ensure insulin always passes the thick fibrous capsule. Finally, we worked on an algorithm that can manage all this automatically. As every individual is different, not every implant will become encapsulated at the same speed, but the right dose of insulin has to be delivered at all times.

While there is still a long way to go before such technology can be implanted into patients, our project presented a novel way to improve the functionality and longevity of implanted drug delivery devices. By monitoring fibrous encapsulation in real-time and autonomously adjusting its response to it, this technology could finally overcome the challenges of the FBR faced by implants. Soft robotic approaches like this one hold great promise for the long-term treatment of chronic diseases.

More about my PhD:

My PhD was part of the DELIVER project – a training network funded by the European Union under Horizon 2020. The Marie Skłodowska-Curie Actions (MSCA) programme gave me the opportunity to spend 1.5 years in industry (Explora Biotech in Venice, Italy) and 1.5 years in academia (University of Galway, Ireland), and allowed me to present at multiple conferences across Europe. If you are considering doing a PhD, it is well worth looking at the MSCA opportunities!

More about our research:

Our article in Science Robotics.
Our review article in Advanced Drug Delivery Reviews.
Dolan, Eimear B., et al. “An actuatable soft reservoir modulates host foreign body response.” Science Robotics 4.33 (2019): eaax7043.
Whyte, William, et al. “Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform.” Nature Communications 13.1 (2022): 4496.