- Bischmattstrasse 12
CH-2544 Bettlach
Switzerland - 0041 32 6442040
Marc Bohner
RMS Foundation, Skeletal Substitute Materials, Faculty Member
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Research Interests: Chemical Engineering, Materials Science, Kinetics, Rheology, Medicine, and 15 moreMultidisciplinary, Vancomycin, Cell line, Ceramics, Humans, Porosity, Viscosity, Staphylococcus aureus, Calcium Phosphates, Anti-Bacterial Agents, X ray diffraction, Alginates, Microbial Sensitivity Tests, Cell Proliferation, and Biocompatible Materials
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Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing... more
Micro-computed tomography (microCT) is commonly used to characterize the three-dimensional structure of bone graft scaffolds before and after implantation in order to assess changes occurring during implantation. The accurate processing of the microCT datasets of explanted β-tricalcium phosphate (β-TCP) scaffolds poses significant challenges because of (a) the overlap in the grey values distribution of ceramic remnants, bone, and soft tissue, and of (b) the resorption of the bone substitute during the implantation. To address those challenges, this article introduces and rigorously validates a new processing technique to accurately distinguish these three phases found in the explanted β-TCP scaffolds. Specifically, the microCT datasets obtained before and after implantation of β-TCP scaffolds were aligned in 3D, and the characteristic grey value distributions of the three phases were extracted, thus allowing for (i) the accurate differentiation between these three phases (ceramic re...
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β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometries for nano-structured composite bone substitutes but were never crystallographically analyzed. In this study, powder X-ray diffraction and... more
β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometries for nano-structured composite bone substitutes but were never crystallographically analyzed. In this study, powder X-ray diffraction and Rietveld refinement revealed a discrepancy between the platelet structure and the known β-TCP crystal model. In contrast, a model featuring partial H for Ca substitution and the inversion of P1O4 tetrahedra, adopted from the whitlockite structure, allowed for a refinement with minimal misfits and was corroborated by HPO4(2-) absorptions in Fourier-transform IR spectra. The Ca/P ratio converged to 1.443 ± 0.003 (n = 36), independently of synthesis conditions. As a quantitative verification, the platelets were thermally decomposed into hydrogen-free β-TCP and β-calcium pyrophosphate which resulted in a global Ca/P ratio in close agreement with the initial β-TCP Ca/P ratio (ΔCa/P = 0.003) and with the chemical composition measured by inductively couple...
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Three resorbable biomaterials were evaluated regarding proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC) in vitro. In a second step, the new biomaterial, calcium-deficient hydroxyapatite (CDHA), was... more
Three resorbable biomaterials were evaluated regarding proliferation and osteogenic differentiation of human bone marrow stromal cells (BMSC) in vitro. In a second step, the new biomaterial, calcium-deficient hydroxyapatite (CDHA), was tested in a pilot in vivo study by subcutaneous implantation in the severe combined immunodeficiency (SCID) mouse. CDHA, beta-tricalcium phosphate (beta-TCP), and demineralized bone matrix (DBM) were seeded with human BMSC and cultured in osteogenic supplements for 3 weeks. In the pilot in vivo study, CDHA was seeded with BMSC and kept in osteogenic media for 2 weeks (group A) before subcutaneous implantation in 8 SCID mice for 3 and 8 weeks. In addition, CDHA seeded with BMSC without prior osteogenic induction (group B) and empty ceramics were implanted in each mouse. Total protein content and the values for specific alkaline phosphatase (ALP) increased significantly in vitro on all matrices, but no significant difference between the groups was noted...
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INTRODUCTION: In the last 3 decades, the number of publications devoted to calcium phosphate (CaP) materials has exploded. This is partly due to the discovery of CaP cements which allows the synthesis of granules and blocks with chemical... more
INTRODUCTION: In the last 3 decades, the number of publications devoted to calcium phosphate (CaP) materials has exploded. This is partly due to the discovery of CaP cements which allows the synthesis of granules and blocks with chemical and physical properties similar to the CaP crystals present in bone. These CaP crystals are octocalcium phosphate (OCP), dicalcium phosphate dihydrate (DCPD), and nanocrystalline apatites, such as calcium-deficient hydroxyapatite (CDHA), hydroxyapatite (HA) or carbonated apatite (CA). So far, there is still a poor understanding of the mechanisms of dissolution-degradation-resorption occurring when these materials are implanted in vivo. The goal of the present communication is to elucidate these mechanisms. For that purpose, the solubility of calcium phosphate phases in serum is calculated. Results are then discussed and compared to in vivo results.
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Polystyrene (PS) latex particles of different sizes were adsorption coated with the polymeric surfactant Pluronic F108 (PEO129-PPO56-PEO129). The commercial surfactant was found to have a bimodal molecular weight distribution. However,... more
Polystyrene (PS) latex particles of different sizes were adsorption coated with the polymeric surfactant Pluronic F108 (PEO129-PPO56-PEO129). The commercial surfactant was found to have a bimodal molecular weight distribution. However, the maximum surface concentrations resulting from adsorption of either the purified high molecular weight component or the composite were identical. An increase in the copolymer surface concentration on 252-nm particles was found to decrease their fibrinogen uptake exponentially. At maximum copolymer surface concentration, the fibrinogen uptake was two orders of magnitude lower than that of bare particles (down from 3.3 mg/m2 to 0.03 mg/m2). This surface protection was equally effective whether the adsorption involved the bimodal polymer surfactant or the purified high molecular weight fraction. The PEO tail mobility was investigated with electron paramagnetic resonance (EPR), and found to increase with an increase in polymer surface concentration. The comparatively slow motion of the PEO chains at low surface concentration indicated that not only the PPO block, but also the PEO blocks interacted hydrophobically with the PS surface. When the copolymer surface concentration was increased, the PEO tails were gradually being released, acquiring higher mobility as the surface became covered by the more strongly binding PPO blocks. Results obtained with F108 coated particles of different sizes showed that particle size had a significant effect on the fibrinogen uptake, with larger particles showing larger fibrinogen uptakes.
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We analyzed the initial adhesion and biofilm formation of Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984) on various bone grafts and bone graft substitutes under standardized in vitro conditions. In parallel,... more
We analyzed the initial adhesion and biofilm formation of Staphylococcus aureus (ATCC 29213) and S. epidermidis RP62A (ATCC 35984) on various bone grafts and bone graft substitutes under standardized in vitro conditions. In parallel, microcalorimetry was evaluated as a real-time microbiological assay in the investigation of biofilm formation and material science research. The materials beta-tricalcium phosphate (beta-TCP), processed human spongiosa (Tutoplast) and poly(methyl methacrylate) (PMMA) were investigated and compared with polyethylene (PE). Bacterial counts (log(10) cfu per sample) were highest on beta-TCP (S. aureus 7.67 +/- 0.17; S. epidermidis 8.14 +/- 0.05) while bacterial density (log(10) cfu per surface) was highest on PMMA (S. aureus 6.12 +/- 0.2, S. epidermidis 7.65 +/- 0.13). Detection time for S. aureus biofilms was shorter for the porous materials (beta-TCP and processed human spongiosa, p < 0.001) compared to the smooth materials (PMMA and PE), with no differences between beta-TCP and processed human spongiosa (p > 0.05) or PMMA and PE (p > 0.05). In contrast, for S. epidermidis biofilms the detection time was different (p < 0.001) between all materials except between processed human spongiosa and PE (p > 0.05). The quantitative analysis by quantitative culture after washing and sonication of the material demonstrated the importance of monitoring factors like specific surface or porosity of the test materials. Isothermal microcalorimetry proved to be a suitable tool for an accurate, non-invasive and real-time microbiological assay, allowing the detection of bacterial biomass without removing the biofilm from the surface.
Research Interests: Materials Science, Biofilms, Multidisciplinary, Quantitative analysis, Microcalorimetry, and 15 moreBone graft, Humans, Biofilm, Staphylococcus aureus, Polyethylene, Real Time, Staphylococcus epidermidis, Porous Material, Quantitative Analysis, Calorimetry, Bone Substitutes, Materials Testing, Sonication, Bacterial Adhesion, and Bone Transplantation
A microsized alpha-tricalcium phosphate (alpha-TCP) powder was calcined at various temperatures (350 degrees... more
A microsized alpha-tricalcium phosphate (alpha-TCP) powder was calcined at various temperatures (350 degrees C<T<800 degrees C) for various durations (1-24h) and the resulting physico-chemical and reactivity changes were measured. Without calcination, the alpha-TCP powder started reacting within minutes after contacting a 0.2M Na(2)HPO(4) solution as measured by isothermal calorimetry. The overall reaction was finished within a few days. After calcination at 350 degrees C< or =T < or =550 degrees C for 24h, no significant changes in the crystalline composition, crystallite size, particle size or specific surface area were noticed. However, the powder reactivity was progressively changed. More specifically, the hydraulic reaction of the powders calcined at 500 and 550 degrees C only started after 2-3h whereas the overall hydraulic reaction was only slightly postponed, suggesting that physical or chemical changes had occurred at the particle surface. As mainly physical changes were detected at the particle surface during calcination at 500 degrees C, it was speculated that the appearance of this reaction delay (=induction time) was due to the disappearance of surface defects during the calcination step, i.e. to the need to create surface defects to induce dissolution and hence reaction.
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Hard cylinders (4.7 x 10 mm) of two kinds of beta-tricalcium phosphate-monocalcium phosphate monohydrate-calcium sulfate hemihydrate (beta-TCP-MCPM-CSH) cements with and without beta-TCP granules (500-1000 microns) were implanted into... more
Hard cylinders (4.7 x 10 mm) of two kinds of beta-tricalcium phosphate-monocalcium phosphate monohydrate-calcium sulfate hemihydrate (beta-TCP-MCPM-CSH) cements with and without beta-TCP granules (500-1000 microns) were implanted into holes drilled in rabbit femoral condyles for up to 16 weeks. Empty cavities were used as control. Cement resorption and new bone formation in the cylinders were evaluated with contact microradiography and quantified through an automatic image analysis system. At 4 weeks, both kinds of cement cylinders were surrounded by new bone. At 8 weeks, except for beta-TCP granules, both cement cylinders were almost completely resorbed and replaced by bone tissue. At 16 weeks the bone in the cavities of both cements recovered a trabecular pattern, but only the bone trabeculae in the initial cavity of the cement with beta-TCP granules became thick and mature. However, the cavities of the empty control were still empty and large. These results show that the beta-TCP-MCPM-CSH cements stimulate bone formation and are rapidly replaced by bone tissue. When added with nonresorbable beta-TCP granules, this cement maintains bone formation for a longer time.
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The rate of dissolution of beta-tricalcium phosphate (beta-Ca3 (PO4 )2 ; beta-TCP) has been measured in the solution system Ca(OH)2 -H3 PO4 -NaOH-HNO3 -H2 O. The effects of different parameters such as pH, temperature, time, and... more
The rate of dissolution of beta-tricalcium phosphate (beta-Ca3 (PO4 )2 ; beta-TCP) has been measured in the solution system Ca(OH)2 -H3 PO4 -NaOH-HNO3 -H2 O. The effects of different parameters such as pH, temperature, time, and saturation have been investigated. At zero saturation, the logarithm of the dissolution rate is a linear function of the pH (log(j 0 ) = 2.02 - 0.82 pH; r 2 = 0.993; in mmol/m2 s), indicating diffusion-limited dissolution. A simple calculation of the theoretical rate of a diffusion-controlled process showed that our data are consistent with theory. Moreover, the activation energy for this process is low (E act = 3.9 kcal/mol) also suggesting that the beta-TCP dissolution is controlled by diffusion processes. At increased saturation, the initial beta-TCP dissolution rate decreases much faster than that predicted assuming a diffusion-controlled model. However, this latter model gives a good prediction of the results if it is assumed that beta-TCP dissolution i...
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A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP... more
A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS).
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Synthetic calcium phosphate bone graft substitutes are widely recognized for their biocompatibility and resorption characteristics in the treatment of large bone defects. However, due to their inherent brittleness, applications in... more
Synthetic calcium phosphate bone graft substitutes are widely recognized for their biocompatibility and resorption characteristics in the treatment of large bone defects. However, due to their inherent brittleness, applications in load-bearing situations always require reinforcement by additional metallic implants. Improved mechanical stability would eliminate the need for non-resorbable metallic implants. In this context a new approach to obtain calcium phosphate scaffolds with improved mechanical stability by texturing the material in specific crystal orientations was evaluated. Texture and reduction of crystal size was achieved by recrystallizing α-TCP blocks into calcium deficient hydroxyapatite (CDHA) under hydrothermal conditions. SEM and XRD analysis revealed the formation of fine CDHA needles (diameter ≈ 0.1-0.5 μm), aligned over several hundreds of micrometers. The obtained microstructures were remarkably similar to the microstructures of the prismatic layer of mollusk shells or enamel, also showing organization at 5 hierarchical structure levels. Brazilian disc tests were used to determine the diametral tensile strength, σdts, and the work-of-fracture, WOF, of the textured materials. Hydrothermal incubation significantly increased σdts and WOF of the ceramic blocks as compared to sintered blocks. These improvements were attributed to the fine and entangled crystal structure obtained after incubation, which reduces the size of strength-determining critical defects and also leads to tortuous crack propagation. Rupture surfaces revealed intergranular tortuous crack paths, which dissipate much more energy than transgranular cracks as observed in the sintered samples. Hence, the refined and textured microstructure achieved through the proposed processing route is an effective way to improve the strength and particularly the toughness of calcium phosphate-based ceramics.
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One α-tricalcium phosphate (α-TCP) powder was either calcined at 500°C to obtain fully crystalline α-TCP or milled for different durations to obtain α-TCP powders containing various amounts of X-ray amorphous tricalcium phosphate (ATCP).... more
One α-tricalcium phosphate (α-TCP) powder was either calcined at 500°C to obtain fully crystalline α-TCP or milled for different durations to obtain α-TCP powders containing various amounts of X-ray amorphous tricalcium phosphate (ATCP). These powders containing between 0 and 71wt.% ATCP and up to 2.0±0.1wt.% β-TCP as minor phase were then hydrated in 0.1M Na2HPO4 aqueous solution and the resulting heat flows were measured by isothermal calorimetry. Additionally, the evolution of the phase composition during hydration was determined by in situ XRD combined with the G-factor method, an external standard method which facilitates the indirect quantification of amorphous phases. Maximum ATCP hydration was reached after about 1h, while that of crystalline α-TCP hydration occurred between 4 and 11h, depending on the ATCP content. An enthalpy of formation of -4065±6kJ/mol (T=23°C) was calculated for ATCP (Ca3(PO4)2), while for crystalline α-TCP (α-Ca3(PO4)2) a value of -4113±6kJ/mol (T=23°C) was determined.
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ABSTRACT Tests were performed to assess the parameters influencing the injectability of cement pastes loaded with large particles, such as porogens or drug-delivery agents. The use of non-setting model pastes permitted to demonstrate that... more
ABSTRACT Tests were performed to assess the parameters influencing the injectability of cement pastes loaded with large particles, such as porogens or drug-delivery agents. The use of non-setting model pastes permitted to demonstrate that two phase separation mechanisms occurred simultaneously, i.e. the separation between liquid and powder, known as filter-pressing phenomenon, and the separation between larger and smaller particles.
In the last 15 years, a large number of commercial ceramic-based cements and putties have been introduced as bone graft substitutes. As a result, large efforts have been made to improve our understanding of the specific properties of... more
In the last 15 years, a large number of commercial ceramic-based cements and putties have been introduced as bone graft substitutes. As a result, large efforts have been made to improve our understanding of the specific properties of these materials, such as injectability, cohesion, setting time (for cements), and in vivo properties. The aim of this manuscript is to summarize our present knowledge in the field. Instead of just looking at scientific aspects, industrial needs are also considered, including mixing and delivery, sterilization, and shelf-life.