New Strontium-based Bioactive Glasses: Physicochemical Reactivity and Delivering Capability of Biologically Active Dissolution Products

International audienceThe development of bone tissue regeneration calls for biomaterials able to release biologically active substances in a controlled manner after implantation. In this context, strontium-doped bioactive glasses are of major interest; their key property relies on the increased kinetics of surface reactions, along with the release of critical concentrations of ionic dissolution products capable of stimulating cellular responses. In this paper, we report a complete evaluation of the in vitro reactivity of new SiO2–CaO–SrO and SiO2–CaO–P2O5–SrO bioactive glasses. In contact with simulated acellular physiological fluids, these materials induce the formation of a calcium phosphate surface layer that closely resembles to the biological apatite present in bones. Compared to strontium-free materials, the dissolution of SiO2–CaO–SrO and SiO2–CaO–P2O5–SrO glasses is reduced. However the surface layer is more quickly transformed into a bone-like apatite phase, according to the kinetics of evolution of the Ca/P atomic ratio. Evidences of the presence of Sr at the glass/biological fluids interface were obtained, along with the demonstration that this element is released in physiological concentrations into the biological environment. Knowing the well-recognized beneficial effects of strontium on cell activity and bone remodeling, this crucial result gives high hopes for the development of innovative applications based on Sr-doped glasses in treatment of osteoporosis and tissue engineering

Micro-PIXE-RBS methods highlighting the influence of phosphorus on the in vitro bioactivity of sol-gel derived glass particles in the SiO2-CaO-P2O5 system

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Influence of mesostructuration on the reactivity of bioactive glasses in biological medium: a PIXE-RBS study

Building mesostructured biomaterials is a challenging and exciting task that has attracted much attention because of their use as drug carriers or drug delivery systems. In the case of bioactive materials, the mesostructuration can also deeply impact their physico-chemical properties and the reactivity. In this study, we show how highly ordered mesoporosity influences the early steps of the biomineralization process and the reactivity in binary (SiO2–CaO) and ternary (SiO2–CaO–P2O5) bioactive glasses. Conventional porous sol–gel glasses were synthesized using a classical route, while mesostructured glasses were developed using a non-ionic surfactant. Textural properties of these materials have been characterized. The in vitro biomineralization process was followed, using Particle Induced X-ray Emission (PIXE) associated to Rutherford Backscattering Spectrometry (RBS), which are efficient methods for a highly sensitive multi-elemental analysis. Elemental maps of silicon, calcium and phosphorus were obtained at a micrometer scale and revealed for the first time a bulk reactivity for mesostructured glasses. This is a major advantage over conventional glasses, for which the first steps of biomineralization are limited to the periphery of the material. Their enhanced bioactivity combined with their possible use as drug-delivery systems make them promising candidates for bone regeneration

Properties of two biological glasses used as metallic prosthesis coatings and after an implantation in body

présentation faite par Y. Barbottea

Structural characterization of Sol-Gel derived Sr-substituted calcium phosphates with anti-osteoporotic and anti-inflammatory properties.

International audienceSol-Gel chemistry has been successfully used to prepare un-doped and Sr-doped calcium phosphate ceramics exhibiting a porous structure. The samples composition is very close to the nominal one. All samples present phase mixtures mainly Hydroxyapatite (HAp) and Tri Calcium Phosphate (Β-TCP). Doping with Sr2+ ions has a clear effect on the proportions of the different phases, increasing the amount of Β-TCP. An amorphous phase is also observed incorporating some 40 % of the total amount of strontium. Strontium ions also substitute for calcium both in HAp and Β-TCP in specific sites that have been determined from Rietveld refinement on synchrotron powder diffraction data. The soluble amorphous and TCP phases are responsible for a beneficial partial release of strontium ions in solution during interactions between the material and biological fluids. Preliminary in vitro study demonstrates anti-inflammatory effect of strontium for human monocytes cultured in contact with calcium phosphates

MMP-2, MMP-9 and their inhibitors TIMP-2 and TIMP-1 production by human monocytes in vitro in the presence of different forms of hydroxyapatite particles.

DOI : 10.1016/j.biomaterials.2003.09.034After calcium-phosphates biomaterials based implantation like hydroxyapatite (HA) coating, particles are released in the periprosthetic tissues. Wear-debris induced fibrous membranes contain macrophage subsets that can produce metalloproteinases (MMPs), which are considered to be key enzymes in extra-cellular matrix turnover. Tissue inhibitors of metalloproteinases (TIMPs) are important regulator of MMPs activity. Interleukin-1 mainly produced by monocytes can also regulate MMPs production. In the present work, we have evaluated the effect of HA particles characteristics (size, shape and sintering temperature) on the MMP-2, -9 and their respective inhibitors TIMP-2, -1 production. Our results demonstrate that sintering temperature (that modify crystal size and surface area) have little effect on MMPs and TIMPs production. Non-phagocytable particles induced more MMP-9, although phagocytable particles induced more IL-1β release. The shape of the particles was the most important factor since needle-shaped particles induced the most significant up-regulated expression of MMPs and IL-1β

STEM and EDXS characterisation of physico-chemical reactions at the periphery of sol-gel derived Zn-substituted hydroxyapatites during interactions with biological fluids

With its good properties of biocompatibility and bioactivity hydroxyapatite (HA) is highly used as bone substitutes and as coatings on metallic prostheses. In order to improve bioactive properties of HA we have elaborated Zn2+ doped hydroxyapatite. Zn2+ ions substitute for Ca2+ cations in the HA structure and four Zn concentrations (Zn/Zn+Ca) were prepared 0.5, 1, 2, 5 % at. To study physico-chemical reactions at the materials periphery, we immersed the bioceramics into biological fluids for delays from 1 day to 20 days. The surface changes were studied at the nanometer scale by scanning transmission electron microscopy associated to energy dispersive X-ray spectroscopy. After 20 days of immersion we observed the formation of a calcium-phosphate layer at the periphery of the HA doped with 5% of zinc. This layer contains magnesium and its thickness was around 200 nm. Formation of this Ca-P-Mg layer represents bioactivity properties of the 5% Zn-substituted hydroxyapatite. This biologically active layer improves properties of HA and will permit a chemical bond between the ceramic and bone

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)