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Per-operative infection is a common complication for bone-graft surgery. Combining antiseptic agents with graft materials may offer a solution by increasing local drug concentration at target sites. Aiming to achieve a sustained local antibiotic (ATB) delivery for a widely applied bone substitute material - hydroxyapatite (HA), we attempted incorporating hydroxypropyl-beta-cyclodextrin polymer (polyHPbetaCD) into microporous HA via impregnating either in a CD monomers mixture solution or a pre-synthesized CD polymer solution, followed by thermal fixation processing. In such functionalised material (CD-HA), polyHPbetaCD could entrap ATBs and release them progressively. Infrared-spectroscopic analysis confirmed the presence of polyHPbetaCD in functionalised HA via both processing pathways; polyHPbetaCD functionalisation yields were quantitated by thermogravimetric analysis for optimising the processing regime. Ciprofloxacin (CFX) and vancomycin (VCM), commonly applied in orthopaedics, have been respectively loaded on CD-HA by dip-coating. For both ATBs, kinetic release test in phosphate buffered saline showed significantly increased initial-burst amount and prolonged release from CD-HA compared with those from non-functionalised HA. Encouragingly, ATBs loaded CD-HA also revealed a prolonged bacteriostatic activity against Staphylococcus aureus and progressively increased cytocompatibility to osteoblasts (MC3T3-E1). Overall, polyHPbetaCD functionalisation on HA could be an effective drug-delivery model for loading different drug molecules in prevention of infection.

The aim of this work was to investigate the consequences of excimer laser irradiation on the physico-chemical and biological properties of polyethylene terephthalate (PET) films, currently used for medical devices. Three PET films from different origins were studied in the present work, chosen with respect to their chemical and physical properties, which are of high importance for ulterior medical application as vascular prostheses. Multiple assays were carried out to characterize the physical and chemical effects of the laser irradiation: surface morphology tests (light microscopy, Dektak profilometer and confocal laser scanning microscopy) showed the strong transformation of the surface with the laser treatment. Contact angle measurements revealed a significant increase of the surface energy for each PET depending on the applied fluency. Finally XPS characterization of the surface demonstrated the appearance of new chemical species favorable for cell attachment. This aspect had to be strongly considered regarding to the multiple biological effects of laser irradiated surfaces on living cells. Different cell culture experiments were carried out with L132 human epithelial cells after 6-days culture: proliferation and vitality rate, cell adhesion and cell morphology. Results clearly revealed that laser treatment improved cell proliferation (up to 140% with respect to controls), vitality (10% higher than controls), morphology and adhesion kinetics (more than 16% of control). A significant correlation (R2=0.906) was also established on one PET between the fluencies of laser treatment and the cellular response. These results emphasized high importance of the choice of the PET material for a medical application: only one of the three considered PET films showed really improved cellular response.

Proliferation and adhesion of mouse (MC3T3-E1) osteoblastic cells and primary human osteoblastic cells were carried out on Ti6Al4V titanium alloy samples with varied surface roughnesses. Mechanically or manually polished surfaces were prepared to produce respectively non-oriented or oriented residual polishing grooves. Sand-blasted surfaces were prepared using 500 microm or 3 mm alumina particles. Surface roughness parameters showed a negative correlation in comparison to proliferation and adhesion parameters. X-ray microprobe chemical surface microanalysis showed complete disturbance of the surface element composition of the Ti6Al4V alloy following sand-blasting treatment. An AlOx-enriched layer was observed on sample surfaces. This may lead to the suspicion that the concomittant effect of surface roughness amplitude and AlOx surface concentration has an effect on osteoblastic cell proliferation and adhesion. These findings show the significance of chemical surface analysis after any surface treatment of titanium-based implants before any biological use.

Porous beta-tricalcium phosphate (betaTCP) has osteoconductive properties. The adsorption of human recombinant bone morphogenetic protein-2 (rhBMP-2) onto TCP could realize an osteoinductive bone substitute. We evaluated it on an animal model using dual-energy X-ray absorptiometry (DEXA) and solid-state 31P nuclear magnetic resonance (NMR) spectroscopy. BetaTCP cylinders loaded with rhBMP-2 were implanted into rabbits' femoral condyle bone defects, and betaTCP alone as control into the contralateral femur. We studied two different doses of rhBMP-2 (10 and 40 microg) on two groups of four animals. Evaluation consisted in radiography, histology, and histomorphometry, DEXA, and NMR spectroscopy using an original method of quantification. With both doses of rhBMP-2, we observed on radiographs an increase of trabecular bone around implants. Histology showed resorption of the ceramic, trabecular bone with osteoblasts and osteoid substance around the implants, and colonization inside the porous betaTCP by new bone formed. Histomorphometry showed that the osteoid surface (OS/BS) was greatest with the high dose of rhBMP-2. The difference was slight between the low dose of rhBMP-2 and control. DEXA showed a dose-dependent increase of bone mineral density of rhBMP-2-loaded betaTCP vs. control. NMR spectroscopy confirmed that the amount of new bone formed in betaTCP was greater when betaTCP carried rhBMP-2, and increased with the dose of rhBMP-2 used. We showed that betaTCP was a good matrix for rhBMP-2, which gave it osteoinductive properties in an orthotopic site, in a dose-dependent manner. Thus, such composite biomaterial seems to be of great interest in reconstructive bone surgery. Further studies are needed in clinical practice to determine optimal doses.

The aim of this paper is to present the potentialities of ultrasounds to investigate the mechanical properties of a cell/substrate interface. The adhesion process plays a major role in the development of osteoblastic cells on various substrates used in orthopedic applications such as metals, bioceramics, etc. Particularly, cell adherence appears to be a critical factor in the colonization process. High-frequency and low-power ultrasounds seem to be an appropriate tool for a nondestructive evaluation of interface properties. First, we present the results obtained with bulk longitudinal and shear waves under an arbitrary incidence over an aluminum-adhesive interface. This study was performed for an industrial application of bonding. The results clearly show the sensitivity of shear waves for the evaluation of the adhesion quality owing to the shear solicitations at the interface they induce. A model of ultrasound interactions with a boundary subject to varying degrees of adhesion has been developed and compared to the experiments. Second, we investigated osteoblastic cell cultures with a high-frequency acoustic microscope working at 50 MHz. The images obtained in the shear mode reveal a better contrast than those obtained in the longitudinal mode. For the time being, these results are qualitative, and theoretical models have to be developed according to the point of view of biologists.

The biological performance of titanium (Ti) particles has been investigated in vitro on murine peritoneal macrophages in a primary culture system. The ultrastructural study revealed an unchanged morphology with respect to controls and the presence of numerous phagocytic vacuoles containing Ti particles as confirmed by X-ray microprobe analyses. The activities of beta-glucuronidase, acid phosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase were determined. All of the enzymes were found to be activated after different exposure times to various Ti concentrations. These activations are qualified as the consequence of cell defence rather than a significant cytotoxic effect. Nevertheless, they indicate a possible inflammatory action of short duration. This investigation provides new arguments for the high biological performance of Ti.

Biomaterial research has been mostly concerned with biocompatibility, i.e. tissue response, of materials for dental or orthopaedic implantation. In this study, the effects of titanium powder on seven bacterial species commonly found in dental plaque or gingival sulcus, were determined by agar incorporation and by liquid medium culture. In neither culture system could any inhibitory or stimulatory activity be detected.

Possible correlations between allergic reactions and the significance of a dental prosthesis or restoration made from one or more of the metals nickel, cobalt and chromium are considered. Described clinical cases are reviewed. These allergic reactions may appear either locally as stomatitis or distantly in the form of general or local contact dermatitis.