Although nanorobots may play critical roles for many applications in the human body such as targeting tumoral lesions for therapeutic purposes, miniaturization of the power source with an effective onboard controllable propulsion and steering system have prevented the implementation of such mobile robots. Here, we show that the flagellated nanomotors combined with the nanometersized magnetosomes of a single Magnetotactic Bacterium (MTB) can be used as an effective integrated propulsion and steering system for devices such as nanorobots designed for targeting locations only accessible through the smallest capillaries in humans while being visible for tracking and monitoring purposes using modern medical imaging modalities such as Magnetic Resonance Imaging (MRI). Through directional and magnetic field intensities, the displacement speeds, directions, and behaviors of swarms of these bacterial actuators can be controlled from an external computer.

The feasibility for in vivo navigation of untethered devices or robots is demonstrated with the control and tracking of a 1.5 mm diameter ferromagnetic bead in the carotid artery of a living swine using a clinical magnetic resonance imaging ͑MRI͒ platform. Navigation is achieved by inducing displacement forces from the three orthogonal slice selection and signal encoding gradient coils of a standard MRI system. The proposed method performs automatic tracking, propulsion, and computer control sequences at a sufficient rate to allow navigation along preplanned paths in the blood circulatory system. This technique expands the range of applications in MRI-based interventions.

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This review paper describes the past, present and future design of therapeutic magnetic carriers (TMMC) being guided in the vascular network using a novel technique known as magnetic resonance navigation (MRN). This targeting method is an extension of magnetic resonance imaging (MRI) technologies. MRN, based on magnetic gradient variation, aims to navigate carriers in real-time along a pre-planned trajectory from their injection site to a targeted area. As such, this approach should minimize systemic distribution of toxic agents loaded into the carriers and improve therapeutic efficacy by delivering a larger proportion of the drug injected. MRN-compatible carriers (shape, material, size, magnetic properties, biocompatibility) have to be designed by taking into consideration the constraints of the medical task and MRN. In the past, as a proof of concept of MRN feasibility, a 1.5-mm ferromagnetic bead was guided in the artery of a living swine with a clinical MRI system. Present day, to aim at medical applications, TMMC have been designed for targeted liver chemoembolization by MRN. TMMC are 50-μm biodegradable microparticles loaded with iron-cobalt nanoparticles and doxorubicin as an antitumor drug. TMMC were selectively guided to the right or left liver lobes in a rabbit model with a clinical MRI scanner upgraded with steering coils. To treat human liver tumor, according to the theoretical MRN model, future TMMC design should take into consideration magnetic nanoparticle properties (nature and loading), MRN platform performances (gradient amplitude and rise time) and vascular hepatic network properties (blood flow velocity and geometry) to optimize the carrier diameter for efficient chemoembolization.

The possibility of automatically navigating untethered microdevices or future nanorobots to conduct target endovascular interventions has been demonstrated by our group with the computer-controlled displacement of a magnetic sphere along a pre-planned path inside the carotid artery of a living swine. However, although the feasibility of propelling, tracking and performing real-time closed-loop control of an untethered ferromagnetic object inside a living animal model with a relatively close similarity to human anatomical conditions has been validated using a standard clinical Magnetic Resonance Imaging (MRI) system, little information has been published so far concerning the medical and technical protocol used. In fact, such a protocol developed within technological and physiological constraints was a key element in the success of the experiment. More precisely, special software modules were developed within the MRI software environment to offer an effective tool for experimenters interested in conducting such novel interventions. These additional software modules were also designed to assist an interventional radiologist in all critical real-time aspects that are executed at a speed beyond human capability, and include tracking, propulsion, event timing and closed-loop position control. These real-time tasks were necessary to avoid a loss of navigation control that could result in serious injury to the patient. Here, additional simulation and experimental results for microdevices designed to be targeted more towards the microvasculature have also been considered in the identification, validation and description of a specific sequence of events defining a new computer-assisted interventional protocol that provides the framework for future target interventions conducted in humans.

MRI signal loss induced by TMMC can serve to track particle accumulation and to assess MRN efficiency.

To prevent the uncontrolled development of a pathogenic biofilm around a dental implant, an antimicrobial drug-release electrospun membrane, set up between the implant and the gingival tissue, was developed by taking several technical, industrial and regulatory specifications into account. The membrane formulation is made of a blend of poly(l-lactic–co–gycolic acid) (PLGA, 85:15) and poly(l-lactic acide–co–ɛ-caprolactone) (PLC, 70:30) copolymers with chlorhexidine diacetate (CHX) complexed with β-cyclodextrin (CD). The amount of residual solvent, the mechanical properties and the drug release kinetics were tuned by the copolymers’ ratio, between 30% and 100% of PLC, and a CHX loading up to 20% w/w. The membranes were sterilized by γ-irradiation without significant property changes. The fiber′s diameter was between 600 nm and 3 µm, depending on the membrane composition and the electrospinning parameters. CHX was released in vitro over 10 days and the bacterial inhibitory concentration, 80 µg·mL−1, was reached within eight days. The optimal membrane, PGLA/PLC/CHX-CD (60%/40%/4%), exhibited a breaking strain of 50%, allowing its safe handling. This membrane and a membrane without CHX-CD were implanted subcutaneous in a rat model. The cell penetration remained low. The next step will be to increase the porosity of the membrane to improve the dynamic cell penetration and tissue remodeling.