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Biomedical subjects

J M Bouler

Publications and source records attributed to J M Bouler.

At least 19 recordsLinked to original sources
PubMed2003

Noninvasive bone replacement with a new injectable calcium phosphate biomaterial.

The use of injectable calcium phosphate (CaP) biomaterials in noninvasive surgery should provide efficient bone colonization and implantation. Two different kinds of injectable biomaterials are presently under development: ionic hydraulic bone cements that harden in vivo after injection, and an association of biphasic calcium phosphate (BCP) ceramic granules and a water-soluble polymer vehicle (a technique particularly investigated by our group), providing an injectable CaP bone substitute (IBS). In our study, we compared these two approaches, using physicochemical characterizations and in vivo evaluations in light microscopy, scanning electron microscopy, and three-dimensional microtomography with synchrotron technology. Three weeks after implantation in rabbit bone, both biomaterials showed perfect biocompatibility and bioactivity, but new bone formation and degradation of the biomaterial were significantly greater for BCP granules than for ionic cement. Newly formed bone developed, binding the BCP granules together, whereas new bone grew only on the surface of the cement, which remained dense, with no obvious degradation 3 weeks after implantation. This study confirms that BCP granules carried by a cellulosic polymer conserve bioactivity and are conducive to earlier and more extensive bone substitution than a carbonated-hydroxyapatite bone cement. The presence of intergranular spaces in the BCP preparation, as shown on microtomography imaging, seems particularly favorable, allowing body fluids to reach each BCP granule immediately after implantation. Thus, the IBS functions as a completely interconnected ceramic with total open macroporosity. This new bone replacement approach should facilitate microinvasive bone surgery and local delivery of bone therapy agents.

Animals↗
PubMed2003

Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials.

This study used synchrotron X-ray microtomography on a micron scale to compare three-dimensional (3D) bone ingrowth after implantation of various calcium phosphate bone substitutes in a rabbit model. The advantage of using this new method for the study of biomaterials was then compared with histomorphometry for analysis of interconnection and bone ingrowth. The study focused on the newly formed bone-biomaterial interface. Macroporous Biphasic Calcium Phosphate (MBCP) ceramic blocks and two different injectable calcium phosphate biomaterials [an injectable bone substitute (IBS) consisting of a biphasic calcium phosphate granule suspension in hydrosoluble polymer and a calcium phosphate cement material (CPC)] were studied after in vivo implantation. Absorption or phase-contrast microtomography was performed with the dedicated set-up at beamline ID22. Experimental spatial resolution was between 1 and 1.4 microm, depending on experimental radiation. All calcium phosphates tested showed osteoconduction. IBS observations after 3D reconstruction showed interconnected bioactive biomaterial with total open macroporosity and complete bone ingrowth as early as 3 weeks after implantation. This experimentation was consistent with two-dimensional histomorphometric analysis, which confirmed its suitability for biomaterials. This 3D study relates the different types of bone substitution to biomaterial architecture. As porosity and interconnection increase, bone ingrowth becomes greater at the expense of the bone substitute: IBS>MBCP>CPC.

Animals↗
PubMed2003

Modification of gene expression induced in human osteogenic and osteosarcoma cells by culture on a biphasic calcium phosphate bone substitute.

Bone hybrids made of bioceramics seeded with mesenchymal or osteoblastic cells are very promising alternatives to autologous bone graft. Along this line, the development of in vitro models, dedicated to analyze the influence of these biomaterials on osteogenic cells, will help to improve the performance of these bone substitutes. In the present work we analyzed the effects of a macroporous biphasic calcium phosphate ceramic (BCP, Triosite) on three different human osteosarcoma cell lines and on human primary osteogenic cells and compared this culture substratum to traditional culture on plastic. We showed that all these osteoblastic cells adhere and proliferate on the trabecular BCP blocks, with a different spatial organization for osteosarcoma cells compared to normal osteogenic cells. We also demonstrated that osteoblastic marker genes such as Cbfa1, type I collagen, osteonectin, osteopontin, and osteocalcin were expressed at similar levels by these cells cultured on either substratum, suggesting that adhesion to BCP does maintain the osteoblastic phenotype of these cells. Next, we provided the first evidence of differences of cytokine expression profiles revealed on this Ca-P ceramic as compared to expression in classical culture. These modifications affected the expression of cytokines such as TGF-beta1, G-CSF, and IL-3 and were quantitatively different between osteosarcoma cells and normal osteogenic cells. Given the role of these cytokines in bone biology and in hematopoiesis, these results obtained in vitro suggest that the BCP ceramic studied here could stimulate osteogenesis in vivo by activating cellular processes during bone formation and healing. This study highlights the notion that the nature of the culture substratum must be taken into account when studying bone cell biology in vitro. Owing to the nature and spatial organization of the BCP, our hypothesis is that culture on BCP is closer to the physiological situation than culture on plastic.

Adolescent↗
PubMed2002

In vitro characterization and in vivo properties of a carbonated apatite bone cement.

This study evaluated the in vivo behavior of an injectable calcium phosphate bone cement implanted in bone defects at the distal end of rabbit femora. After 3 weeks, samples were harvested and processed for undecalcified sectioning. Scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared microspectroscopy showed direct contact of bone and cement without soft tissue interposition, biocompatibility, and bioactivity with osteoconductive properties.

Animals↗
PubMed2001

Macroporous biphasic calcium phosphate ceramics versus injectable bone substitute: a comparative study 3 and 8 weeks after implantation in rabbit bone.

Macroporous biphasic calcium phosphate ceramics (MBCP) and a calcium phosphate injectable bone substitute (IBS), obtained by the association of biphasic calcium phosphate (BCP) ceramic granules and an aqueous solution of a cellulosic polymer, were compared in the same animal model. The two tested biomaterials were implanted in distal femoral osseous defects in rabbits. Qualitative and quantitative histological evaluation was performed three and eight weeks after implantation to investigate bone colonization and ceramic biodegradation associated with the two bone substitutes. Both biomaterials expressed osteoconduction properties and supported the apposition of a well-mineralized lamellar newly-formed bone. Bone colonization occurred much earlier and faster for IBS than for MBCP implants, although the respective rates of newly-formed bone after eight weeks of implantation did not differ significantly. For both biomaterials, ceramic resorption occurred regularly throughout the implantation period, though to a greater extent with IBS than with MBCP implants. The associated polymer in IBS produced intergranular spaces allowing body fluids to reach each BCP ceramic granule immediately after implantation, which may have favored osteoblastic activity, new bone formation and ceramic resorption. This completely interconnected open macroporosity could account for the earlier and more satisfactory bone substitution achieved with IBS.

Journal Article↗
PubMed2001

Study of the maturation of the organic (type I collagen) and mineral (nonstoichiometric apatite) constituents of a calcified tissue (dentin) as a function of location: a Fourier transform infrared microspectroscopic investigation.

Fourier transform infrared microspectroscopy (FTIRM) was used to investigate the organic and mineral phases of a calcified tissue (dentin) as a function of its location from predentin toward enamel. Thin dentin slices (decalcified or not) were fixed in formaldehyde and embedded in glycolmethylmethacrylate (GMA). Fixation did not denature collagen, and GMA did not interact with organic or mineral constituents of dentin. The v1v3 PO4 domain was studied in particular in order to estimate mineral maturity and amide I, II, A, and B to obtain data on protein conformation. The results showed that dentin apatite became increasingly mature (stoichiometric) from the mineralization front toward the enamel, especially through loss of HPO4(2-) groups and vacancies. Moreover, collagen fibrils became less and less hydrated, suggesting that intrafibrillar mineralization partially dehydrated the collagen. Combined study of the organic and mineral fractions of calcified tissues may help clarify their relationships in physiological and pathological tissues.

Adolescent↗
PubMed2000

Biphasic calcium phosphates: influence of three synthesis parameters on the HA/beta-TCP ratio.

Hydroxyapatite (HA) contents measurements were conducted on eight biphasic calcium phosphate (BCP) samples obtained by sintering calcium-deficient apatite formed previously by hydrolyzing a dicalcium phosphate dihydrate (DCPD) powder. We evaluated the influences and interactions of three synthesis factors: alkalinity, process duration, and concentration of the water suspension in DCPD. Those parameters were varied simultaneously between two limit levels. Experiments used a factorial design method (FDM) allowing optimization of the number of samples as well as statistical analysis of results. FDM showed that HA content, in a defined experimental area, can be described by a first-order polynomial equation in which the initial alcalinity and the DCPD/water ratio are the major influences. Experiment prove that pH measured at the end of the hydrolysis was predictive of the HA content in the final BCP. This study leads up to an isoresponse line diagram which will allow the synthesis of some BCP with fitted HA/beta-tricalcium phosphate ratios.

Biocompatible Materials↗
PubMed2000

Crystal polymer interaction with new injectable bone substitute; SEM and Hr TEM study.

A composite constituted of calcium phosphate (CaP) granules and a hydrophilic polymer as a carrier (hydroxy-propyl-methyl cellulose, HPMC) was developed to be an injectable bone substitute (IBS, CNRS patent). IBS is a composite and not an ionic cement. The composite obtained is ready to use and sterile. Chemical interactions between organic and inorganic components appeared during the association of the two. The interactions of the CaP and the polymer have been studied using scanning electron microscopy (SEM), electron microprobe (EDX), and high-resolution transmission electron microscopy (HrTEM) SEM revealed a degradation of the granules into smaller particles while EDX was unable to show significant changes in the Ca/P ratio during aging of the composite. With Hr TEM, however, we observed hydrolysis (process of dissolution and precipitation) from the surface to about 13 nm into the HA crystals and occasional dissolution with precipitation of beta-TCP crystals. In HA, the first zone of interaction consisted of a single layer of small globular crystals of 2 to 3 nm in diameter. Numerous lattice patterns in all three axes could be observed. Under the globular crystals zone, the inter-reticular distances of the single crystals appeared enlarged by 1.2% (from 0.817 to 0.827 nm). The enlargement seems to correspond to diffusion of HPO(4) into the crystal lattice. In beta-TCP crystals, dissolution was observed to be several nanometers deep, but globular surface precipitation rarely was observed. With time or after steam sterilization, no changes were observed. These data demonstrate the strong interactions of the hydrophylic polymer with calcium phosphate, but only in the first several nanometers of thickness.

Bone Substitutes↗
PubMed2000

Chemical transformation of some biologically relevant calcium phosphates in aqueous media during a steam sterilization.

The purpose of this study was to investigate the effect of steam sterilization on some biologically relevant calcium phosphates: CaHPO4 . 2H2O (DCPD), calcium deficient apatite (CDA) and biphasic calcium phosphate (BCP). Suspensions of 0.2 g of each calcium phosphate compound with 5.0 ml of deionized water were prepared and steam sterilized in an autoclave (20 min at 121 degrees C). After sterilization the suspensions were filtered and the dried solids characterized with scanning electron microscopy, IR-spectroscopy and X-ray diffraction. The pH and calcium concentrations of the filtrates were determined with ion selective electrodes. Similar measurements were made with the same samples which were not sterilized. The sterilization procedure was found to result in the dehydration of DCPD and hydration of calcium oxide incorporated into the BCP. Solution pH was observed to change from 7.3 to 5.5 for the solutions in equilibrium with DCPD and from 8.5 to 10.6 for those in equilibrium with BCP. Minor changes both with the solid and liquid phases were found to occur during the steam sterilization of CDA. These results indicate that steam sterilization may have different effects on different calcium phosphate suspensions: it can result in dehydration of DCPD, fast hydration for CaO in BCP, but no significant effect on CDA.

Journal Article↗
PubMed1999

Influence of biphasic calcium phosphate granulometry on bone ingrowth, ceramic resorption, and inflammatory reactions: preliminary in vitro and in vivo study.

Calcium-phosphate ceramics used in surgery, as bone-bonding materials, are currently available in different forms (blocks, granules, etc.). However, progress in noninvasive surgery has favored the development of injectable composite materials associating a polymeric and a dusty mineral phase. The purpose of this study was the in vivo evaluation of biphasic calcium phosphate of various grains sizes, to elucidate the role of granulometries in ceramic degradation/resorption, bone ingrowth, and inflammatory reactions. Three particle sizes were compared: 10-20, 80-100, and 200-400 microm. The 10-20-microm powders provided the best bone ingrowth, with a higher resorption/degradation rate in conjunction with stronger early inflammatory reactions. The 200-400-microm powders showed higher bone ingrowth than 80-100-microm ones, indicating that properties of cell recruitment for osseous apposition and mechanical support for bone bonding may both play a role in both ingrowth mechanisms. Our results suggest that the strong inflammatory reaction in 10-20-microm granulated powders was due to a faster reversal of the resorption/apposition sequence in bone. This may have resulted from massive release of bone ingrowth factors, which implies that the brief inflammatory process observed in the early stages of implantation was favorable to the osteoconduction process.

Bone Development↗
PubMed1999

Kinetic study of bone ingrowth and ceramic resorption associated with the implantation of different injectable calcium-phosphate bone substitutes.

This study investigated the in vivo performance of two composite injectable bone substitutes (IBS), each with different calcium-phosphate particles granulometries [40-80 (IBS 40-80) and 200-500 microm (IBS 200-500)]. These biomaterials were obtained by associating a biphasic calcium-phosphate (BCP) ceramic mineral phase with a 3% aqueous solution of a cellulosic polymer (hydroxy-propyl-methyl-cellulose). Both materials were injected for periods of 2, 3, 8, or 12 weeks into bone defects at the distal end of rabbit femurs. Quantitative results on new bone formation, BCP resorption, and staining for tartrate-resistant acid phosphatase (TRAP) activity were studied for statistical purposes. Measurements with scanning electron microscopy and image analysis showed that the final rates of newly formed bone were similar for both tested IBS after 12 weeks of implantation. Bone colonization occurred more extensively during early implantation times for IBS 40-80 than for IBS 200-500. For the latter, BCP degradation occurred regularly throughout the implantation period, whereas it was very intensive during the first 2 weeks for IBS 40-80. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than for IBS 200-500 regardless of implantation time. With the granulometry of either mineral phase, both tested IBS supported extensive bone colonization, which was greater than that previously reported for an equivalent block of macroporous BCP. The resorption-bone substitution process seemed to occur earlier and faster for IBS 40-80 than for IBS 200-500. Both tested IBS expressed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability.

Animals↗
PubMed1999

Biphasic calcium phosphate/hydrosoluble polymer composites: a new concept for bone and dental substitution biomaterials.

Calcium phosphate materials have been increasingly employed in orthopedic and dental applications in recent years and are now being developed for use in noninvasive surgery or as carriers for drug delivery systems. We developed an injectable bone substitute (IBS) constituted of biphasic calcium phosphate and a hydrosoluble polymer as a carrier. In vivo biocompatibility and biofunctionality of IBS were tested in rabbits using implants in osseous and nonosseous areas. The results obtained demonstrated that the concept of IBS, a filler without initial mechanical properties but able to be rapidly resorbed and replaced by newly formed bone, can be applied to new surgical applications in orthopedic surgery, maxillofacial surgery, and dentistry for pulp capping and root filling.

Animals↗
PubMed1999

Short-term effects of mineral particle sizes on cellular degradation activity after implantation of injectable calcium phosphate biomaterials and the consequences for bone substitution.

This in vivo study investigated the influence of two calcium phosphate particle sizes (40-80 microm and 200-500 microm) on the cellular degradation activity associated with the bone substitution process of two injectable bone substitutes (IBS). The tested biomaterials were obtained by associating a biphasic calcium phosphate (BCP) ceramic mineral phase and a 3% aqueous solution of a cellulosic polymer (hydroxypropylmethylcellulose). Both were injected into osseous defects at the distal end of rabbit femurs for 2- and 3-week periods. Quantitative results for tartrate-resistant acid phosphatase (TRAP) cellular activity, new bone formation, and ceramic resorption were studied for statistical purposes. Positive TRAP-stained degradation cells were significantly more numerous for IBS 40-80 than IBS 200-500, regardless of implantation time. BCP degradation was quite marked during the first 2 weeks for IBS 40-80, and bone colonization occurred more extensively for IBS 40-80 than for IBS 200-500. The resorption-bone substitution process occurred earlier and faster for IBS 40-80 than IBS 200-500. Both tested IBS displayed similar biological efficiency, with conserved in vivo bioactivity and bone-filling ability. Differences in calcium phosphate particle sizes influenced cellular degradation activity and ceramic resorption but were compatible with efficient bone substitution.

Acid Phosphatase↗
PubMed1999

Nuclear magnetic resonance spectroscopy of bone substitutes.

Calcium phosphate bone replacement biomaterials are widely used in different applications. Structure, composition, and organization are, before implantation, analyzed with different methods. Among them, X-ray diffraction is a recognized test. As bioresorption produces more amorphous material, the process is observed and quantified via scanning electron microscopy. Comparatively high-resolution 31P solid-state nuclear magnetic resonance spectroscopy is able to analyze raw ceramics composition and to estimate osteoformation.

Animals↗
PubMed1999

Injectable bone substitute using a hydrophilic polymer.

We studied a new injectable biomaterial for bone and dental surgery consisting of a hydrophilic polymer as matrix and bioactive calcium phosphate (CaP) ceramics as fillers. This material is composed of complex fluids whose flow is determined by the laws of rheology. We investigated the macromolecular effects on this composite in a tube. The stability of the polymer and the mixture is essential to the production of a ready-to-use injectable biomaterial. These flow properties are necessary to obtain CaP bioactivity in a dental canal or bone defect during percutaneous surgery. Macromolecules provide spaces between CaP ceramic granules and facilitate the role of the biological agents of bone substitution.

Animals↗
PubMed1999

Elaboration conditions influence physicochemical properties and in vivo bioactivity of macroporous biphasic calcium phosphate ceramics.

Two different preparations of biphasic calcium phosphate (BCP) were characterized in vitro: BCP1 from a mechanical mixture of hydroxyapatite (HA) and beta-tricalcium phosphate (beta-TCP) powders, and BCP2 from calcination of a calcium-deficient apatite (CDA). The structural, physicochemical and mechanical parameters of these two preparations were investigated, and two different macroporous BCP1 (MBCP1) and BCP2 MBCP2) implants were manufactured and implanted in rabbit bone for in vivo bioactivity studies. Scanning electron microscopy observations showed that MBCP1 implants had a significantly higher degradation rate (P<0.0001) than MBCP2 implants. This was probably caused by the presence of calcium oxide impurities in BCP1 and the more intimate mixture and stable ultrastructure of BCP2. No significant difference about the newly formed bone rate in these two BCP preparations was observed. Very slight variations in sintering conditions appeared to influence the biodegradation behavior of the two MBCP implants despite their identical HA/-TCP ratios and similar porosity. Precise and complete in vitro characterization enabled us to understand and predict in vivo degradation behavior.

Journal Article↗
PubMed1999

A new injectable calcium phosphate biomaterial for immediate bone filling of extraction sockets: a preliminary study in dogs.

BACKGROUND: Many different bone substitutes, such as autografts, allografts or synthetic biomaterials have been proposed to restore alveolar bone loss and support efficient placement of dental implants. This experimental study evaluated the osteoconductive properties of an injectable bone substitute (IBS) composed of a polymeric carrier and a calcium phosphate mineral phase, used to fill mandibular and maxillary canine extraction sockets. METHODS: The polymer was a cellulose derivative (methyl-hydroxy-propyl-cellulose, MHPC), and the mineral phase consisted of granules of biphasic calcium phosphate (BCP) ceramics 200 to 500 microm in diameter. Mandibular and maxillary premolars extracted from 3 dogs (a total of 60 extraction sites) were immediately treated with the IBS or left unfilled as control sites. Animals were sacrificed 3 months after implantation and all extraction sockets were prepared for histological evaluation. RESULTS: Qualitative histological studies showed that the IBS was able to support the extensive apposition of well-mineralized newly formed lamellar bone over the entire socket surface and appeared to prevent alveolar ridge bone loss in treated extraction sites. Quantitative evaluation showed that the amount of newly formed bone was significantly higher in mandibular than maxillary extraction sockets for both treated and control sites. CONCLUSIONS: An injectable bone substitute composed of a polymeric carrier and calcium phosphate was effective in enhancing the bone fill of extraction sockets. This approach may prove promising for periodontal lesions. The material expressed osteoconductive capacities, and the biological properties of the mineral phase were conserved.

Animals↗