Engulfment of ceramic particles by fibroblasts does not alter cell behavior.

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium-zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 µg ml-1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium-zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium-zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium-zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.

Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns.

Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

Poly-cyclodextrin functionalized porous bioceramics for local chemotherapy and anticancer bone reconstruction.

The progress in bone cancer surgery and multimodal treatment concept achieve only modest improvement in the overall survival, due to failure in clearing out residual cancer cells at the surgical margin and extreme side-effects of adjuvant postoperative treatments. Our study aims to propose a new method based on cyclodextrin polymer (polyCD) functionalized hydroxyapatite (HA) for achieving a high local drug concentration with a sustained release profile and a better control of residual malignant cells via local drug delivery and promotion of the reconstruction of bone defects. PolyCD, a versatile carrier for therapeutic molecules, can be incorporated into HA (bone regeneration scaffold) through thermal treatment. The parameters of polyCD treatment on the macroporous HA (porosity 65%) were characterized via thermogravimetric analysis. Good cytocompatibility of polyCD functionalized bioceramics was demonstrated on osteoblast cells by cell vitality assay. An antibiotic (gentamicin) and an anticancer agent (cisplatin) were respectively loaded on polyCD functionalized bioceramics for drug release test. The results show that polyCD functionalization leads to significantly improved drug loading quantity (30% more concerning gentamicin and twice more for cisplatin) and drug release duration (7 days longer concerning gentamicin and 3 days longer for cisplatin). Conclusively, this study offers a safe and reliable drug delivery system for bioceramic matrices, which can load anticancer agents (or/and antibiotics) to reduce local recurrence (or/and infection).

An in vitro study of composites of poly(L-lactide-co-ε-caprolactone), ß-tricalcium phosphate and ciprofloxacin intended for local treatment of osteomyelitis.

Osteomyelitis is a bacterial disease that can become chronic, and treatment often includes a surgical operation to remove infected bone. The aim of this study was to develop and investigate in vitro bone filling composite materials that release ciprofloxacin to kill any remaining bacteria and contain bioceramic to help the bone to heal. Three composites of poly(L-lactide-co-ε-caprolactone), ß-tricalcium phosphate and ciprofloxacin were compounded using twin-screw extrusion and sterilized by gamma irradiation. Drug release and degradation of the composites were investigated in vitro for 52 weeks. The composite with 50 wt% of ß-TCP had the most promising ciprofloxacin release profile. The ceramic component accelerated the drug release that occurred in three phases obeying first-order kinetics. Inhibition zone testing using bioluminescence showed that the released ciprofloxacin had effect in eradicating a common osteomyelitis causing bacteria Pseudomonas aeruginosa. During the in vitro degradation test series, molar weight of the polymer matrix of the composites decreased rapidly. Additionally, (1)H-NMR analysis showed that the polymer had blocky structure and the comonomer ratio changed during hydrolysis. The tested composites showed great potential to be developed into bone filler materials for the treatment of osteomyelitis or other bone related infections.

Biological activity of respirable industrial fibres treated to mimic residence in the lung.

The durability of fibres in the lung environment after deposition could be a key factor in determining whether they accumulate to a sufficient tissue dose to cause pathological change. There is a shortage of information on the relative durabilities of respirable industrial fibres of various types. We describe a strategy for assessing the ability of different fibre types to persist in the lung milieu and to retain their biological activity. This is particularly important for the development of mesothelioma, where the long latent time that characterises this disease would be expected to exclude, from culpability, fibres that are not durable. We have combined a pre-treatment step in pH 5.0 or 7.0 with an assay that relies on the ability of fibres to damage the mesothelium. The long-term aim is to assess the impact that treatment in various pH solutions has on (a) fibre size/number, (b) loss of key elements, (c) the ability to damage the mesothelium. Such information should enable us to better predict the potential of fibres to cause mesothelioma.

The metabolism of ceramic and non-ceramic forms of uranium dioxide after deposition in the rat lung.

Ceramic and non-ceramic forms of uranium dioxide, produced industrially, were administered to rats either by inhalation or as an aqueous suspension which was injected directly into the pulmonary region of the lungs. The results showed that: 1 both materials should be assigned to inhalation class Y as defined by the International Commission on Radiological Protection; 2 whilst the translocation of uranium to the blood for the non-ceramic UO2 was about twice that obtained for the ceramic form, the two dioxides were unlikely to be differentiated on the basis of their lung retention kinetics; 3 the distribution of uranium amongst body tissues and the relationship between systemic content and cumulative urinary excretion indicated that it was transported in the hexavalent form; 4 in addition to air sampling procedures, lung radioactivity counting measurements could be used to advantage for assessing occupational exposures; 5 the exposure limits should be based on radiation dose rather than chemical toxicity.