Antibacterial properties and regenerative potential of Sr2+ and Ce3+ doped fluorapatites; a potential solution for peri-implantitis.

Scaffolds and implants in orthopaedics and regenerative dentistry usually fail because of bacterial infections. A promising solution would be the development of biomaterials with both significant regenerative potential and enhanced antibacterial activity. Working towards this direction, fluorapatite was synthesised and doped with Sr2+ and Ce3+ ions in order to tailor its properties. After experiments with four common bacteria (i.e. E. Coli, S. Aureus, B. Subtilis, B. Cereus), it was found that the undoped and the Ce3+ doped fluorapatites present better antibacterial response than the Sr2+ doped material. The synthesised minerals were incorporated into chitosan scaffolds and tested with Dental Pulp Stem Cells (DPSCs) to check their regenerative potential. As was expected, the scaffolds containing Sr2+-doped fluorapatite, presented high osteoconductivity leading to the differentiation of the DPSCs into osteoblasts. Similar results were obtained for the Ce3+-doped material, since both the concentration of osteocalcin and the RUNX2 gene expression were considerably higher than that for the un-doped mineral. Overall, it was shown that doping with Ce3+ retains the good antibacterial profile of fluorapatite and enhances its regenerative potential, which makes it a promising option for dealing with conditions where healing of hard tissues is compromised by bacterial contamination.

Exogenous mineralization of hard tissues using photo-absorptive minerals and femto-second lasers; the case of dental enamel.

A radical new methodology for the exogenous mineralization of hard tissues is demonstrated in the context of laser-biomaterials interaction. The proposed approach is based on the use of femtosecond pulsed lasers (fs) and Fe3+-doped calcium phosphate minerals (specifically in this work fluorapatite powder containing Fe2O3 nanoparticles (NP)). A layer of the synthetic powder is applied to the surface of eroded bovine enamel and is irradiated with a fs laser (1040 nm wavelength, 1 GHz repetition rate, 150 fs pulse duration and 0.4 W average power). The Fe2O3 NPs absorb the light and may act as thermal antennae, dissipating energy to the vicinal mineral phase. Such a photothermal process triggers the sintering and densification of the surrounding calcium phosphate crystals thereby forming a new, dense layer of typically ∼20 µm in thickness, which is bonded to the underlying surface of the natural enamel. The dispersed iron oxide NPs, ensure the localization of temperature excursion, minimizing collateral thermal damage to the surrounding natural tissue during laser irradiation. Simulated brushing trials (pH cycle and mechanical force) on the synthetic layer show that the sintered material is more acid resistant than the natural mineral of enamel. Furthermore, nano-indentation confirms that the hardness and Young's modulus of the new layers are significantly more closely matched to enamel than current restorative materials used in clinical dentistry. Although the results presented herein are exemplified in the context of bovine enamel restoration, the methodology may be more widely applicable to human enamel and other hard-tissue regenerative engineering. STATEMENT OF SIGNIFICANCE: In this work we provide a new methodology for the mineralisation of dental hard tissues using femtosecond lasers and iron doped biomaterials. In particular, we demonstrate selective laser sintering of an iron doped fluorapatite on the surface of eroded enamel under low average power and mid-IR wavelength and the formation of a new layer to substitute the removed material. The new layer is evaluated through simulated brushing trials and nano-indentation. From the results we can conclude that is more acid resistant than natural enamel while, its mechanical properties are superior to that of current restorative materials. To the best of our knowledge this is the first time that someone demonstrated, laser sintering and bonding of calcium phosphate biomaterials on hard tissues. Although we here we discuss the case of dental enamel, similar approach can be adopted for other hard tissues, leading to new strategies for the fixation of bone/tooth defects.

ß-pyrophosphate: A potential biomaterial for dental applications.

Tooth hypersensitivity is a growing problem affecting both the young and ageing population worldwide. Since an effective and permanent solution is not yet available, we propose a new methodology for the restoration of dental enamel using femtosecond lasers and novel calcium phosphate biomaterials. During this procedure the irradiated mineral transforms into a densified layer of acid resistant iron doped ß-pyrophosphate, bonded with the surface of eroded enamel. Our aim therefore is to evaluate this densified mineral as a potential replacement material for dental hard tissue. To this end, we have tested the hardness of ß-pyrophosphate pellets (sintered at 1000°C) and its mineral precursor (brushite), the wear rate during simulated tooth-brushing trials and the cytocompatibility of these minerals in powder form. It was found that the hardness of the ß-pyrophosphate pellets is comparable with that of dental enamel and significantly higher than dentine while, the brushing trials prove that the wear rate of ß-pyrophosphate is much slower than that of natural enamel. Finally, cytotoxicity and genotoxicity tests suggest that iron doped ß-pyrophosphate is cytocompatible and therefore could be used in dental applications. Taken together and with the previously reported results on laser irradiation of these materials we conclude that iron doped ß-pyrophosphate may be a promising material for restoring acid eroded and worn enamel.

Experimental investigation of the flow of a blood analogue fluid in a replica of a bifurcated small artery.

The scope of this work is to study the pulsatile flow of a blood mimicking fluid in a micro channel that simulates a bifurcated small artery, in which the Fahraeus-Lindqvist effect is insignificant. An aqueous glycerol solution with small amounts of xanthan gum was used for simulating viscoelastic properties of blood and in vivo flow conditions were reproduced. Local flow velocities were measured using micro Particle Image Velocimetry (µ-PIV). From the measured velocity distributions, the wall shear stress (WSS) and its variation during a pulse were estimated. The Reynolds numbers employed are relatively low, i.e. similar to those prevailing during blood flow in small arteries. Experiments both with a Newtonian and a non-Newtonian fluid (having asymptotic viscosity equal to the viscosity of the Newtonian one) proved that the common assumption that blood behaves as a Newtonian fluid is not valid for blood flow in small arteries. It was also shown that the outer wall of the bifurcation, which is exposed to a lower WSS, is more predisposed to atherosclerotic plaque formation. Moreover, this region in small vessels is shorter than the one in large arteries, as the developed secondary flow decays faster. Finally, the WSS values in small arteries were found to be lower than those in large ones.