L’Hocine Yahia

Automatic navigation of an untethered device in the artery of a living animal using a conventional clinical magnetic resonance imaging system

The feasibility for in vivo navigation of untethered devices or robots is demonstrated with the control and tracking of a 1.5mm diameter ferromagnetic bead in the carotid artery of a living swine using a clinical magnetic resonance imaging (MRI) 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.The feasibility for in vivo navigation of untethered devices or robots is demonstrated with the control and tracking of a 1.5mm diameter ferromagnetic bead in the carotid artery of a living swine using a clinical magnetic resonance imaging (MRI) 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.

Induction of macrophage apoptosis by ceramic and polyethylene particles in vitro.

The purpose of this study was to investigate in vitro the presence of apoptotic cell death after macrophage stimulation with different ceramic (Al2O3 and ZrO2) and high density polyethylene (HDP) particles. We also analyzed the effects of particle size, concentration, and composition. The J774 mouse macrophage cell line was exposed to commercial particles of different sizes (up to 4.5 microm) and concentrations (up to 500 particles per macrophage). Fluorescence microscopy and DNA laddering were used to investigate the presence of apoptosis in cell cultures after 24 h of incubation. Fluorescence microscopy of propidium iodide stained cells showed two characteristic morphological features that occur in apoptotic cells, namely nuclear condensation and heterogeneity of stain uptake. The effect of ceramic particles on apoptotic nuclear morphology was size- and concentration-dependent and reached a plateau above 150 particles per macrophage at 1.3 microm. With regards to composition, we did not find any difference in cell morphology between Al2O3 and ZrO2. Ceramic and HDP particles induced DNA fragmentation into oligonucleosomes as evidenced by DNA laddering, another characteristic of apoptosis. The induction of DNA laddering was size- and concentration-dependent whereas particle composition (Al2O3 vs. ZrO2 and Al2O3 vs. HDP) had no effect. In conclusion, our results demonstrated that ceramic and HDP particles induce macrophage apoptotic cell death in vitro and open doors for possible modulation of debris-induced periprosthetic osteolysis.

Nanoparticle and Protein Corona

Nanoparticles and other nanomaterials are increasingly considered for use in biomedical applications such as imaging, drug delivery, and hyperthermic therapies. Thus, understanding the interaction of nanomaterials with biological systems becomes key for their safe and efficient application. It is increasingly being accepted that the surface of nanomaterials would be covered by protein corona upon their entrance to the biological medium. The biological medium will then see the achieved modified surface of nanomaterials, and therefore further cellular/tissue responses depend on the composition of corona. In this chapter, we describe the corona variations according to the physicochemical properties of nanomaterials (e.g., size, shape, surface charge, surface functional groups, and hydrophilicity/hydrophobicity). Besides the nanomaterials’ effects, the role of environment factors, such as protein source and slight temperature variations, is discussed in details.

Shape memory polymer foams for cerebral aneurysm reparation: effects of plasma sterilization on physical properties and cytocompatibility.

Shape memory polyurethanes (SMPUs) represent promising candidate materials for aneurysm embolization, since they could enable clinical problems still associated with these clinical procedures to be overcome. In this work, we report on the characterization of physicochemical, thermomechanical and in vitro interface properties of two SMPU foams (Cold Hibernated Elastic Memory, CHEM), proposed as a material for embolization devices in minimally invasive procedures. Moreover, because device sterilization is mandatory for in vivo applications, effects on the properties of the foams after plasma sterilization were also evaluated. Both foams (CHEM 3520 and CHEM 5520) showed excellent shape recovery ability (recovery rate, R(r), up to 99%) in conventional shape recovery tests, performed at constant heating rate. Transition temperatures (T(trans)), determined by tandelta peaks in dynamic mechanical analysis (DMA), were 32.2 and 45.1 degrees C, for CHEM 3520 and 5520, respectively. The value of T(trans) affects shape memory ability in the recovery test at 37 degrees C, which simulates the behavior after implantation of the device: in fact, R(r) was significantly higher for lower T(trans) foam (R(r) approximately 82% and R(r) approximately 46%, respectively, for CHEM 3520 and CHEM 5520). After plasma sterilization performed by a Sterrad sterilization system, an increase in open porosity was observed: this is probably due to the sterilization cycle; however, no effects on shape recovery behavior were observed. Furthermore, plasma treatment had no significant effect on L929 cells in in vitro cytotoxicity tests, performed on cell culture medium extracts in contact with foams for up to 7 days. Moreover, direct cytocompatibility tests showed a good colonization and growth from L929 cells on CHEM foams, suggesting the effectiveness of an in vivo healing process. All these results seem to suggest that CHEM foams could be advantageously used for manufacturing devices for mini-invasive embolization procedures of aneurysms.

A computer-assisted protocol for endovascular target interventions using a clinical MRI system for controlling untethered microdevices and future nanorobots.

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.

Chemico-physical modifications induced by plasma and ozone sterilizations on shape memory polyurethane foams

Thermally activated shape memory polyurethane foams are promising materials for minimally invasive surgical procedures. Understanding their physical and chemical properties, in vitro response and effects of sterilization is mandatory when evaluating their potential as biomaterials. In this work, we report on the characterization of two Cold Hibernated Elastic Memory (CHEM) foams before and after two novel low-temperature sterilization techniques (plasma and ozone). Foams have different transition temperatures (Ttrans), as determined by Tanδ peaks in DMA tests, that depend on their chemical composition: both foams possess excellent shape recovery ability (Recovery Rate up to 99%) in conventional shape recovery tests. Plasma sterilization (Sterrad® sterilization system) resulted in a slight increase of open porosity, but no effects on bulk chemical and thermo-mechanical properties were observed. Ozone sterilization had a stronger effect on foams morphology, both in terms of an evident rupture of pore walls and surface oxidation. These modifications affected both thermomechanical and shape recovery behavior. Furthermore, plasma sterilized foams cytocompatibility was investigated with L929 fibroblast cell line in vitro, showing a good adhesion and proliferation, as confirmed by SEM observation and Alamar blue assay. The obtained results contribute to define the role of shape memory foams as biomaterials and open novel questions on the role of sterilization technique effects on cellular solids.

Nanoscale surface characterization of biphasic calcium phosphate, with comparisons to calcium hydroxyapatite and β-tricalcium phosphate bioceramics.

OBJECTIVES It is our aim to understand the mechanisms that make calcium phosphates, such as bioactive calcium hydroxyapatite (HA), and biphasic calcium (BCP) and β-tricalcium (β-TCP) phosphates, desirable for a variety of biological applications, such as the filling of bone defects. METHODS Here, we have characterized these materials by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), time-of-flight secondary ion mass spectroscopy (TOF-SIMS) and laser granulometry. RESULTS SEM shows clearly that BCP is a matrix made of macro-organized microstructure, giving insight to the specially chosen composition of the BCP that offers both an adequate scaffold and good porosity for further bone growth. As revealed by laser granulometry, the particles exhibit a homogeneous size distribution, centered at a value somewhat larger than the expected 500 μm. XPS has revealed the presence of adventitious carbon at all sample surfaces, and has shown that Ca/P and O/Ca ratios in the outer layers of all the samples differ significantly from those expected. A peak-by-peak XPS comparison for all samples has revealed that TCP and BCP are distinct from one another in the relative intensities of their oxygen peaks. The PO3(-)/PO2(-) and CaOH+/Ca+ TOF-SIMS intensity ratios were used to distinguish among the samples, and to demonstrate that the OH- fragment, present in all the samples, is not formed during fragmentation but exists at the sample surface, probably as a contaminant. CONCLUSIONS This study provides substantial insight into the nanoscale surface properties of BCP, HA and β-TCP. Further research is required to help identify the effect of surfaces of these bioceramics with proteins and several biological fluids. CLINICAL RELEVANCE The biological performance of implanted synthetic graft bone biomaterials is strongly influenced by their nanosurface characteristics, the structures and properties of the outer layer of the biomaterial.

A comparative physicochemical, morphological and magnetic study of silane-functionalized superparamagnetic iron oxide nanoparticles prepared by alkaline coprecipitation.

The characterization of synthetic superparamagnetic iron oxide nanoparticle (SPION) surfaces prior to functionalization is an essential step in the prediction of their successful functionalization, and in uncovering issues that may influence their selection as magnetically targeted drug delivery vehicles (prodrugs). Here, three differently functionalized magnetite (Fe3O4) SPIONs are considered. All were identically prepared by the alkaline coprecipitation of Fe(2+) and Fe(3+) salts. We use X-ray photoelectron spectroscopy, electron microscopy, time-of-flight SIMS, FTIR spectroscopy and magnetic measurements to characterize their chemical, morphological and magnetic properties, in order to aid in determining how their surfaces differ from those prepared by Fe(CO)5 decomposition, which we have already studied, and in assessing their potential use as drug delivery carriers.

Solid state synthesis of carbon-encapsulated iron carbide nanoparticles and their interaction with living cells

Superparamagnetic carbon-encapsulated iron carbide nanoparticles (NPs), Fe7C3@C, with unique properties, were produced from pure ferrocene by high pressure-high temperature synthesis. These NPs combine the merits of nanodiamonds and SPIONs but lack their shortcomings which limit their use for biomedical applications. Investigation of these NPs by X-ray diffraction, electron microscopy techniques, X-ray spectroscopic and magnetic measurement methods has demonstrated that this method of synthesis yields NPs with perfectly controllable physical properties. Using magnetic and subsequent fractional separation of magnetic NPs from residual carbon, the aqueous suspensions of Fe7C3@C NPs with an average particle size of ∼25 nm were prepared. The suspensions were used for in vitro studies of the interaction of Fe7C3@C NPs with cultured mammalian cells. The dynamics of interaction of the living cells with Fe7C3@C was studied by optical microscopy using time-lapse video recording and also by transmission electron microscopy. Using novel highly sensitive cytotoxicity tests based on the cell proliferation assay and long-term live cell observations it was shown that the internalization of Fe7C3@C NPs has no cytotoxic effect on cultured cells and does not interfere with the process of their mitotic division, a fundamental property that ensures the existence of living organisms. The influence of NPs on the proliferative activity of cultured cells was not detected as well. These results indicate that the carbon capsules of Fe7C3@C NPs are air-tight which could offer great opportunities for future use of these superparamagnetic NPs in biology and medicine.

Personalized implant for high tibial opening wedge: Combination of solid freeform fabrication with combustion synthesis process

In this work a new generation of bioceramic personalized implants were developed. This technique combines the processes of solid freeform fabrication (SFF) and combustion synthesis (CS) to create personalized bioceramic implants with tricalcium phosphate (TCP) and hydroxyapatite (HA). These porous bioceramics will be used to fill the tibial bone gap created by the opening wedge high tibial osteotomy (OWHTO). A freeform fabrication with three-dimensional printing (3DP) technique was used to fabricate a metallic mold with the same shape required to fill the gap in the opening wedge osteotomy. The mold was subsequently used in a CS process to fabricate the personalized ceramic implants with TCP and HA compositions. The mold geometry was designed on commercial 3D CAD software. The final personalized bioceramic implant was produced using a CS process. This technique was chosen because it exploits the exothermic reaction between P2O5 and CaO. Also, chemical composition and distribution of pores in the implant could be controlled. To determine the chemical composition, the microstructure, and the mechanical properties of the implant, cylindrical shapes were also fabricated using different fabrication parameters. Chemical composition was performed by X-ray diffraction. Pore size and pore interconnectivity was measured and analyzed using an electronic microscope system. Mechanical properties were determined by a mechanical testing system. The porous TCP and HA obtained have an open porous structure with an average 400 µm channel size. The mechanical behavior shows great stiffness and higher load to failure for both ceramics. Finally, this personalized ceramic implant facilitated the regeneration of new bone in the gap created by OWHTO and provides additional strength to allow accelerated rehabilitation.