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Bioresorbable implantable medical devices show great potential for applications requiring medical care over well-defined periods of time. Such implants naturally degrade and resorb in the body, which eliminates adverse long-term effects or the need for a secondary surgery to extract the device. Since biodegradable materials are water-soluble, their fabrication requires special care and relies solely on dry processing steps without exposure to aqueous solutions. Another challenge is the in vivo powering of medical implants that are only constituted of biodegradable materials. The objective of this thesis is to develop a fully biodegradable drug delivery implant with multiple reservoirs for on-demand wireless drug delivery. Then to integrate and miniaturize all the components to reduce the volume of material used, whilst limiting the fabrication process complexity. The design, fabrication and characterization of selectively addressable biodegradable magnesium microheaters is presented, together with the development of an innovative microfabrication process. It consists of four steps: physical vapor deposition, photolithography, ion beam etching and resist stripping. The microheaters consist of several spiral resonators. An electrical current is induced in a specific spiral resonator when coupling an external magnetic field at a matching frequency. Adding a meander to the resonator increases the current density locally and creates a hot-spot. Slightly varying the geometry of the devices enables the tuning of their resonance frequency and makes them selectively addressable. The frequency-selective wireless heating of different resonators is demonstrated in air and in liquid, plus enables the melting of the surrounding environment. Additionally, small geometrical variations by design induce large frequency shifts. As a result, several resonators with multiple resonance frequencies can be integrated in one device without much of an increase in diameter. These microheaters are used as power receivers and triggering elements to selectively release drugs from multiple reservoirs in a wirelessly controlled drug delivery capsule. This prototype is made of non-biodegradable materials to demonstrate the feasibility of the concept. It consists of a 3D printed capsule with several reservoirs filled with drugs. Each reservoir is sealed with a polyimide membrane and a resonant gold microheater on top of it. These microheaters are used to thermally trigger the breaking of the membranes and release the drugs from the reservoirs. The powering and triggering mechanisms are combined into one element, minimizing the volume of material and maximizing the drug-to-implant volume ratio. The successful fabrication of leak-free capsules and the wireless release of liquid from the reservoirs is demonstrated. This capsule is compatible with the drug requirements needed in the context of local analgesia after a knee arthroplasty. However, to have a clinical outcome, it should be fabricated from biodegradable materials to prevent a second surgery to extract the device. Finally, to explore the development of a fully biodegradable version of the device, biodegradable microheaters are fabricated on biodegradable membranes by transfer printing. The capsules are then micro-molded from biodegradable elastomers.
Florian Frédéric Vincent Breider, Vinhteang Kaing