The present work deals with a study on the physical characteristics of stoichiometric hydroxyapatite microspheres produced by spray-drying process through different operating conditions. Obtained ...hydroxyapatite microspheres are intended to be used as powder feedstock in powder bed selective laser processing additive manufacturing technologies where the flowability and the particle size distribution of the powder feedstock are of special importance. The powders produced at different spray-drying operating parameters were evaluated by analysing the particle size, shape, moisture, and agglomerates strength. Spray air pressure (0.25–2 bars) and the solid content of the slurries (10–50% wt.) were the most influent parameters to control the final particle size distribution, whereas the higher process recovery rate (79%) was obtained at specific values of inlet temperature (250 °C), spray air pressure (2 bar), and feed rate (4.9 kg.h−1). A 5 wt% of polyvinyl alcohol as an organic binder to the ceramic part was found to increase the strength of the granules. The flowability of the produced hydroxyapatite microspheres (x50 = 64 μm; span = 1.77) was found to fulfil the defined feedstock requirements (e.g., Hausner ratio < 1.25), without alteration of the physico-chemical properties of the material. These promising results confirm the use of a spray dryer as an efficient method for the production of hydroxyapatite microspheres for powder bed selective laser processing.
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•Powder bed fusion feedstock with improved flowability properties may be achieved by spray-drying process•Spray-drying process parameters can tune the hydroxyapatite microspheres particle size distribution•Polyvinyl alcohol as organic binder improves the granules breakage resistance•HA physico-chemical properties and crystallinity remain unaltered after the spray-drying process
Plasma-spray (PS) is the most common technique used to cover orthopaedic titanium-based implant surfaces with hydroxyapatite (HA - Ca10(PO4)6OH2). The objective of the current work was to explore the ...influence of the precursor nature and characteristics (mainly powder size, Ca/P ratio, and density) on the morphology and the microstructure of HA coatings, deposited either by conventional atmospheric plasma spray (APS) or by rf-suspension plasma spray (rf-SPS). Two powders with different size distribution, density and shape were sprayed with same operating APS conditions. In parallel two water-based suspensions with distinct particle size and chemistry (Ca/P ratio) were implemented in rf-SPS. The morphology of both APS and rf-SPS coatings observed by SEM exhibits micro and sub-micro sized structures respectively, with similar porosity and thickness. The difference in precursor particle size does not affect the coating structure in rf-SPS, unlike in APS conditions. Superimposition of topography and phases maps performed from profilometry and Raman cartographies showed no direct correlation between the surface profile and composition. But such analysis highlighted the heterogeneity of the phases composing the coating surface, opening the possibility of a better understanding of biological behaviour.
•Rf-SPS gives access to highly crystallized hydroxyapatite coatings and finer structures than APS.•Precursor characteristics such as particle size and Ca/P ratio influence the final state of decomposition and microstructure.•Raman cartography displays a heterogeneous distribution of the phases on the coating surface.
Stoichiometric hydroxyapatite (HAP) is a prominent biomaterial, notably used as coating on metal bone prostheses. High chemical purity and a specific particle size distribution are the main ...properties for such an application. Based on industrial practice, a reference synthesis was first performed in a lab-scale stirred reactor. Improvements were then suggested by varying the physicochemical and hydrodynamic conditions. The shear rate within the reactor, characterized by the mean Kolmogorov micro-scale, has a strong impact on the final agglomerate size distribution. By maintaining a rather high mixing rate and a high temperature, the duration of the synthesis can be reduced considerably without affecting the HAP purity provided the pH is properly regulated. This consists of imposing acidic conditions during a short period just after the initial formation of large aggregates and then setting the pH at above 7.5 to ensure the production of pure stoichiometric HAP.
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•The shear rate mainly impacts the particle size distribution of synthesized HAP.•Pure HAP can be produced at 75 °C ensuring a relevant pH regulation.•Under specific physico-chemical conditions, maturation has only a small effect on HAP.
L’hémophilie acquise est une maladie auto-immune exceptionnelle. Le traitement immunosuppresseur a pour objectif d’enrayer la production d’autoanticorps inhibiteurs des facteurs VIII (FVIII) ou IX ...(FIX) de la coagulation. Une association corticothérapie-cyclophosphamide est recommandée en première intention. À partir de notre expérience au CHU de Nîmes, nous discutons la place du rituximab dans l’arsenal thérapeutique.
Nous rapportons une étude observationnelle monocentrique rétrospective. Nos données sont discutées à la lumière des données de la littérature, en particulier des cohortes EACH2 et SACHA.
Huit patients dont 7 avec un anticorps anti-FVIII ont été consécutivement inclus à partir de 2005. L’âge moyen était de 68,5 ans avec une prédominance masculine (62,5 %). Les manifestations hémorragiques étaient habituellement spontanées et superficielles. Une pathologie, notamment auto-immune ou néoplasique, était associée chez 5 des 8 patients. Un traitement hémostatique dit « by-passant » était prescrit pour 3 patients. Du rituximab était prescrit pour 5 patients, dont trois fois en première intention, et toujours associé à la corticothérapie. Trois patients ont reçu une association cyclophosphamide/cortisone, deux ont été traités exclusivement par une corticothérapie orale. La rémission était obtenue chez tous les patients, sans rechute ultérieure. Le délai moyen pour obtenir la rémission sous rituximab (après la première injection) était de 32,5jours (10–143). Les résultats observés dans notre série de patients sont cohérents avec les données de la littérature.
Le rituximab semble être un traitement efficace et bien toléré de l’hémophilie acquise auto-immune. Sa place reste cependant à préciser.
Autoimmune acquired haemophilia is a rare autoimmune disease. The purpose of immunosuppressive therapy is to stop the production of autoantibodies that inhibit clotting factors VIII or IX. A corticosteroids-cyclophosphamide combination is recommanded as first-line therapy. From our experience at the University Hospital of Nîmes, we discuss the place of rituximab in the therapeutic arsenal.
We report a monocentric observational retrospective study. Our data are discussed in light of literature data, in particular cohorts EACH2 and SACHA.
Eight patients (7 with FVIII anibodies) were consecutively included from 2005. The average age was 68.5 years with a male predominance (62.5%). Bleeding manifestations were usually spontaneous and superficial. A pathology, mostly autoimmune or neoplastic, was associated in 5/8 patients. A “by-pass” haemostatic treatment was prescribed for 3/8 patients. Rituximab was prescribed for 5/8 patients, three times as first-line therapy, and always associated with corticosteroids. Three patients received a cyclophosphamid/cortisone combination, two were treated exclusively with oral corticosteroids. Remission was obtained in all patients, without subsequent relapse. The average time to obtain remission under rituximab (after the first injection) was 32.5 days (10–143). The results observed in our series of patients are consistent with the data from the literature.
Rituximab appears to be an effective and well-tolerated treatment for autoimmune acquired haemophilia. However, its place remains to be specified.
Plasma-sprayed hydroxyapatite (HA) coatings are used on metallic implants to improve osseointegration and bone growth. The purpose of this work was to determine the microstructure and composition of ...HA coatings obtained with a newly developed low energy plasma spray mini-gun employing an HA feedstock powder with smaller granulometry than that commonly used.
The microstructure and the phase composition of the coatings obtained by varying the number of mini-gun runs were examined using scanning electron microscopy, X-ray diffraction and Fourier transform infrared and micro-Raman spectroscopy. In all cases, the results indicate the presence of an amorphous phase and oxyapatite in the coatings due to hydroxyl group removal. No other foreign crystalline phases were detected. The absence of foreign phases was attributed to the fast cooling rate of the small particles used in the experiments and the low amount of energy employed with the mini-gun.
Decomposition in the υ
1PO
4 region of the Raman spectra allowed a semi-quantitative evaluation of the phase contents as a function of the number of runs. Micro-Raman spectroscopy appears to be a powerful technique providing comprehensive and localised information concerning calcium phosphate phases in coatings.
► Development of low energy plasma spray mini-gun for small sized implants. ► Highly crystalline hydroxyapatite thin coatings were produced. ► Amorphous phase and oxyapatite were limited and no foreign phases are detected. ► Highlight of μRaman spectroscopy which provided information about phases in coatings.
This study aims to investigate the feasibility of generating three-dimensional scaffold structures by robocasting 3D printing for bone tissue engineering and anatomical model applications. ...Robocasting is an additive manufacturing process that generates parts directly from CAD draws in a layer-wise manner, enabling the construction of complex 3D structures with controlled chemistry and specific interconnected porosity. Our strategy was based on the reactivity of the involved components in mineral bone cement or plaster self-setting pastes, but the simultaneity of manufacturing process and chemical setting reactions required a careful adaptation of paste formulations to secure enough time to fabricate a 3D scaffold under homogeneous extruding conditions at room temperature. The two self-setting pastes reactions studied in the present work were the transformation of calcium sulphate hemi-hydrate into gypsum and a mixture of brushite and vaterite into apatite. Additives such as carboxymethyl cellulose (CMC) or polyvinyl alcohol (PVA) were introduced in limited amounts (2–3% for CMC and 9–13% for PVA) in the self-setting paste formulations to favour extrusion while achieving self-standing brands. To complete the 3D scaffold setting reaction, a post-drying protocol was developed. 3D parts of various sizes and architectures were produced. Their crystalline phase and chemical composition characterisations allowed establishing the progress of the chemical setting reaction for all the pastes. A rheological study allowed defining a common trend for all the extruded pastes. Compression tests presented great mechanical properties of plaster 3D samples, particularly improved by the presence of PVA, while water absorption study presented suitable values for all the compositions, according to their different applications.
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•We report the deposition by MAPLE of biomimetic apatite coatings on Ti substrates.•This is the first report of MAPLE deposition of hydrated biomimetic apatite films.•Biomimetic apatite powder was ...synthesized by double decomposition process.•Non-apatitic environments, of high surface reactivity, are preserved post-deposition.•We got the MAPLE complete transfer as thin film of a hydrated, delicate material.
We report the deposition by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique of biomimetic nanocrystalline apatite coatings on titanium substrates, with potential application in tissue engineering. The targets were prepared from metastable, nanometric, poorly crystalline apatite powders, analogous to mineral bone, synthesized through a biomimetic approach by double decomposition process. For the deposition of thin films, a KrF* excimer laser source was used (λ=248nm, τFWHM≤25ns). The analyses revealed the existence, in synthesized powders, of labile non-apatitic mineral ions, associated with the formation of a hydrated layer at the surface of the nanocrystals. The thin film analyses showed that the structural and chemical nature of the nanocrystalline apatite was prevalently preserved. The perpetuation of the non-apatitic environments was also observed. The study indicated that MAPLE is a suitable technique for the congruent transfer of a delicate material, such as the biomimetic hydrated nanohydroxyapatite.
Les angiodysplasies (AD) sont une cause non négligeable de saignement digestif dont la prévalence augmente avec l’âge. Le traitement repose en première intention sur les gestes d’hémostase réalisés ...durant une endoscopie mais les récidives sont fréquentes. S’il n’y a pas encore de recommandations précises, des approches pharmacologiques se développent en seconde ligne parmi lesquelles les traitements anti-angiogéniques.
Nous rapportons le cas d’une patiente de 90 ans suivie depuis 2012 pour des AD digestives nécessitant des transfusions (36 culots globulaires CGR au total) et des perfusions de fer itératives (10g de fer intraveineux IV en 2017) et ce malgré des thermocoagulations au plasma argon répétées en endoscopie (duodénale×8, cæcale×2). Elle avait pour antécédent une insuffisance rénale modérée et ne prenait pas de traitement antiagrégant ou anticoagulant. En 2016 la prescription d’acide tranéxamique et de sandostatine avait permis d’espacer les épisodes transfusionnels. En 2017, un bilan complémentaire était réalisé suite à la découverte d’un TCA allongé (normal auparavant) conduisant au diagnostic de maladie de Willebrand acquise, motivant l’administration de facteur Willebrand humain. Le bilan étiologique ne retrouvait pas de syndrome lymphoprolifératif associé, uniquement un rétrécissement aortique non serré. En 2018, la recrudescence de méléna, avec une augmentation des besoins transfusionnels à 4 CGR par mois, motivait la prescription de lénalidomide à la posologie de 5 puis 10mg/jour permettant de réduire les besoins transfusionnels de 50 % (seulement 3 mois de recul). En raison d’une baisse des polynucléaires neutrophiles et des plaquettes nous n’avons pas pu augmenter à la posologie de 15mg.
Discussion Cette observation illustre la difficulté de prise en charge des AD avec hémorragie digestive récurrente malgré un traitement endoscopique adapté.
Il a été démontré que les patients porteurs d’AD ainsi que les sujets âgés ont un taux supérieur de vascular endothelial growth factor (VEGF). En effet, le vieillissement provoque des modifications veineuses et capillaires responsables d’une hypoxie chronique, induisant une augmentation du taux de VEGF sérique 1.
Le déficit acquis en facteur Willebrand joue également un rôle en stimulant l’angiogenèse via des voies intra- et extracellulaires impliquant l’integrine αvβ3 et Ang-2 stimulant VEGFR-2 2. Il semble donc pertinent d’utiliser des traitements diminuant l’angiogénèse dépendante du VEGF. Le lénalidomide est un dérivé synthétique du thalidomide, indiqué dans le traitement du myélome multiple osseux et dans l’anémie avec dépendance transfusionnelle due à un syndrome myélodysplasique. Ses propriétés anti-angiogéniques reposent sur l’inhibition du facteur de transcription NF-kB (augmentation de l’apoptose), sur la diminution du VEGF sanguin et sur l’inhibition de la migration des cellules endothéliales 1. Pour les 5 patients atteints d’AD rapportés par Khatri et al., il permet de réduire le nombre d’endoscopies (0,25 versus 5,5 après et avant traitement p=0,001), de culots globulaires consommés (pas de transfusion pour 3/5 patients) ainsi que le risque de morbimortalité lié aux transfusions 3. Cela est d’autant plus intéressant chez le sujet âgé fragile. Toutefois ce traitement n’est pas dénué d’effets secondaires bien que moindres comparativement au thalidomide, raison de notre choix de molécule (myélotoxicité, risque thrombotique, cancers secondaires). Une administration intermittente pourrait améliorer la tolérance par exemple : 3 semaines on–1 semaine off ou 2 semaines on–2 semaines off3.
Le lénalidomide est une alternative attrayante dans le traitement des AD, en particulier chez le sujet âgé fragile en permettant d’éviter le recours aux transfusions sanguines et hospitalisations itératives. Son efficacité et sa tolérance restent cependant à déterminer au cours d’études complémentaires pour en déterminer sa place exacte dans la stratégie thérapeutique des AD.
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Blended chitosan-to-biomimetic apatite films deposited by combinatorial MAPLE.Amorphous thin films with rough morphology.Composition gradient of films monitored by FTIR and XPS, ...confirmed by Raman.Antimicrobial activity controlled by chitosan content of films.
Chitosan/biomimetic apatite thin films were grown in mild conditions of temperature and pressure by Combinatorial Matrix-Assisted Pulsed Laser Evaporation on Ti, Si or glass substrates. Compositional gradients were obtained by simultaneous laser vaporization of the two distinct material targets. A KrF* excimer (λ=248nm, ϿFWHM=25ns) laser source was used in all experiments. The nature and surface composition of deposited materials and the spatial distribution of constituents were studied by SEM, EDS, AFM, GIXRD, FTIR, micro-Raman, and XPS. The antimicrobial efficiency of the chitosan/biomimetic apatite layers against Staphylococcus aureus and Escherichia coli strains was interrogated by viable cell count assay.
The obtained thin films were XRD amorphous and exhibited a morphology characteristic to the laser deposited structures composed of nanometric round shaped grains. The surface roughness has progressively increased with chitosan concentration. FTIR, EDS and XPS analyses indicated that the composition of the BmAp-CHT C-MAPLE composite films gradually modified from pure apatite to chitosan.
The bioevaluation tests indicated that S. aureus biofilm is more susceptible to the action of chitosan-rich areas of the films, whilst the E. coli biofilm proved more sensible to areas containing less chitosan.
The best compromise should therefore go, in our opinion, to zones with intermediate-to-high chitosan concentration which can assure a large spectrum of antimicrobial protection concomitantly with a significant enhancement of osseointegration, favored by the presence of biomimetic hydroxyapatite.
To systematically present and interpret the current literature on research and treatment perspectives for mandibular osteoradionecrosis (mORN) in the field of biomaterials.
A systematic review of the ...literature using the “Synthesis without meta-analysis” (SWiM) methodology was performed on PubMed, Embase and Cochrane, focusing on the implantation of synthetic biomaterials for bone reconstruction in mORN in humans and/or animal models. The primary endpoints were the composition, efficacy on mORN and tolerance of the implanted synthetic biomaterials.
Forty-seven references were obtained and evaluated in full-text by two assessors. Ten (8 in humans and 2 in animal models) met the eligibility criteria and were included for analysis. Materials most often comprised support plates or metal mesh (5 of 10 cases) in combination with grafts or synthetic materials (phosphocalcic ceramics, glutaraldehyde). Other ceramic/polymer composites were also implanted. In half of the selected reports, active compounds (molecules, growth factors, lysates) and/or cells were associated with the reconstruction material. The number of articles referring to implantation of biomaterials for the treatment of mORN was small, and the properties of the implanted biomaterials were generally poorly described, thus limiting a thorough understanding of their role.
In preventing the morbidity associated with some reconstructive surgeries, basic research has benefitted from recent advances in tissue engineering and biomaterials to repair limited bone loss.
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