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Summary Porous biomaterials promote osseointegration. We have prepared porous titanium cylinders by additive manufacturing from titanium beads. Two types of morphology were tested: cylinders with geometric pores or mimicking trabecular microarchitecture. Cylinders were decontaminated and cleaned by HF/HNO3 to remove unmelted balls. Surgical implantation in ewes was performed under general anesthesia and the animals were housed for 90 and 270 days. The femoral condyles were collected and analyzed by nanoCT, embedded in pMMA and analyzed by histomorphometry. No significant difference was found in terms of bone volume or bone/titanium interface between the two types of cylinders. There was no evolution over time except for the mineralization rates which decreased, reflecting the effect of the aging of the animals. The influence of the pores (geometrical or “natural”) did not influence osseointegration. HF/HNO3 etching treatments are effective on the outermost surfaces but do not seem to reach the central cavities of the samples. Finally, osseointegration seems to occur only in the few millimeters around the periphery of the implants and does not extend in the center. This is explained by the absence of stress transmission within the very rigid metal cylinders, preventing bone modeling and remodeling.

Large bone defects are a challenge for orthopedic surgery. Natural (bone grafts) and synthetic biomaterials have been proposed but several problems arise such as biomechanical resistance or viral/bacterial safety. The use of metallic foams could be a solution to improve mechanical resistance and promote osseointegration of large porous metal devices. Titanium cylinders have been prepared by additive manufacturing (3D printing/rapid prototyping) with a geometric or trabecular microarchitecture. They were implanted in the femoral condyles of aged ewes; the animals were left in stabling for 90 and 270 days. A double calcein labeling was done before sacrifice; bones were analyzed by histomorphometry. Neither bone volume, bone/titanium interface nor mineralization rate were influenced by the cylinder’s microarchitecture; the morphometric parameters did not significantly increase over time. Bone anchoring occurred on the margins of the cylinders and some trabeculae extended in the core of the cylinders but the amount of bone inside the cylinders remained low. The rigid titanium cylinders preserved bone cells from strains in the core of the cylinders. Additive manufacturing is an interesting tool to prepare 3D metallic scaffolds, but microarchitecture does not seem as crucial as expected and anchoring seems limited to the first millimeters of the graft.

Legg Calve Perthes disease (LCPD) is a developmental abnormality that usually affects young small breed dogs. Although the etiology is still uncertain, the pathogenesis is very similar to that described in humans. Diagnosis with physical examination and medical imaging is relatively easy. Treatments offered in dogs, mainly surgical, are also presented. Legg Calve Perthes disease has many similarities between children and puppies. Dog is therefore an interesting spontaneous model of aseptic osteonecrosis.

[EN] In this work, the capability of imaging biomarkers obtained from multivariate curve resolution-alternating least squares (MCR-ALS), in combination with those obtained from first and second-generation pharmacokinetic models, have been studied for improving prostate cancer tumor depiction using partial least squares- discriminant analysis (PLS-DA). The main goal of this work is to improve tissue classification properties selecting the best biomarkers in terms of prediction. A wrapped double cross-validation method has been applied for the variable selection process. Using the best PLS-DA model, prostate tissues can be classified obtaining 13.4% of false negatives and 7.4% of false positives. Using MCR-ALS biomarkers yields the best models in terms of parsimony and classification performance., This research has been supported by "Generalitat Valenciana (Conselleria d'Educacio, Investigacio, Cultura I Esport)" under the project AICO/2016/061.

Cross-linked hyaluronic acid (HyAR) increases the local concentration of growth factors. We compared β-TCP osseointegration in old and young ewes with/without HyAR addition. A blind tunnel was drilled on the medial femoral condyle of each knee in nine young and nine old ewes and was filled with β-TCP, β-TCP + HyAR or left unfilled. Double labeling with calcein allowed histodynamic analysis. Ewes were sacrificed at 84 days and the knees were harvested. MicroCT provided histomorphometric parameters: trabecular bone volume, residual volume of biomaterial. Histodynamic parameters were: mineralization rate, mineralized surfaces, bone formation rate. A non-parametric ANOVA and post hoc test analyzed differences between subgroups. Osseointegration of β-TCP was similar in the aged/young grafted groups. Trabecular bone volume was significantly increased versus ungrafted animals (p

International audience; The inferior alveolar nerve (IAN) is a sensitive branch of the trigeminal nerve. It has an intra-bone path in the mandible, inside the mandibular canal, where it is accompanied by lymph, venous and arterial vessels. We have studied the mandibular canal in human mandibles and in some laboratory animals (mice, rats, rabbits and cats). Microcomputed tomography evidenced that the walls of the canal are made with thin plates of trabecular bone with numerous fenestrations. This aspect is evidenced in dentate subjects and become more evident in edentulous subjects with atrophy of the alveolar bone. In rats and mice, the wall of the canal is also clearly composed of trabecular plates coming from the surrounding alveolar bone of the mandible. In the rabbit, similar findings are also observed but the trajectory of the canal is more difficult to identify. In the cat, the floor of the canal is composed of the cortical bone from the basilar cortex of the mandible and the roof has a trabecular nature. Vascular injections of gelatin-barium evidenced the arterial trajectories inside the bone in rats and humans. Undecalcified bone sections in human evidenced the histological aspect of the IAN and its connective sheets. Some nervous bundles can be observed outside the epineurium. Bone remodeling is observed on the wall of the mandibular canal. These descriptive findings have a clinical relevance in dental implantology or mandibular surgery.; Le nerf alvéolaire inférieur (IAN) est une branche sensible du nerf trijumeau. Il a un trajet intra-osseux dans la mandibule, à l’intérieur du canal mandibulaire, où il est accompagné des vaisseaux lymphatiques, veineux et artériels. Nous avons étudié le canal mandibulaire dans des mandibules humaines et chez certains animaux de laboratoire (souris, rats, lapins et chats). La micro-tomodensitométrie aux rayons X montre que les parois du canal sont composées de fines plaques d’os trabéculaire avec de nombreuses perforations. Cet aspect est mis en évidence chez les sujets dentés et devient plus évident chez les sujets édentés qui ont une atrophie de l’os alvéolaire. Chez le rat et la souris, la paroi du canal est également clairement composée de plaques trabéculaires provenant de l’os alvéolaire environnant. Chez le lapin, des observations similaires sont également faites mais la trajectoire du canal est plus difficile à identifier. Chez le chat, le plancher du canal est composé d’os cortical du cortex basal de la mandibule et le toit présente une nature trabéculaire. Les injections intravasculaires de gélatine-baryum mettent en évidence les trajectoires artérielles à l’intérieur de l’os chez les rats et l’homme. Des coupes osseuses en histologie réalisée sans décalcification chez l’homme témoignent de l’aspect microscopique du IAN et de ses différentes enveloppes conjonctives. Certains faisceaux nerveux peuvent être observés en dehors de l’épinèvre. Le remodelage osseux est observé sur la paroi du canal mandibulaire. Ces résultats descriptifs ont une pertinence clinique en implantologie dentaire ou en chirurgie mandibulaire.

[EN] Multivariate Curve Resolution (MCR) has been applied on prostate Diffusion Weighted-Magnetic Resonance Images (DW-MRI). Different physiological-based modeling approaches of the diffusion process have been submitted to validation by sequentially incorporating prior knowledge on the MCR constraints. Results validate the biexponential diffusion modeling approach and show the capability of the MCR models to find, characterize and locate the behaviors related to the presence of an early prostate tumor., The authors want to thank prof. Anna de Juan for her comments and help in using the software for this study. This research work was partially supported by the Spanish Ministry of Economy and Competitiveness under the project DPI 2011-28112-004-02.

Muscle and bone masses are highly correlated and muscles impose large loads on bone. Muscle wasting that accompanies bone loss has been poorly investigated. 21 female mice were spread into seven groups. At day 0, 18 mice received Botulinum toxin (BTX) injection in the quadriceps muscle to induce paralysis of the right hind limb; the left contralateral side was used as control. Mice were sacrificed at 7, 14, 21, 28, 56 and 90 days post-injection. A remaining group was sacrificed at day 0. Trabecular bone volume was determined by microcomputed tomography (microCT) at the distal femur and tibia proximal metaphyses on both sides. Limbs were immersed in an HgCl2 solution allowing muscle visualization by microCT. On 2D sections, the cross-sectional areas and form-factors were measured for the quadriceps at mid-thigh and gastrocnemius at mid-leg and these muscles were dissected and weighed. Bone volume decreased in the paralysed side. Bone loss was maximal at 56 days followed by recuperation at 90 days. The cross-sectional areas of gastrocnemius and quadriceps were significantly lower in the paralysed limb from 7 days; the decrease was maximum at 21 days for the gastrocnemius and 28 days for the quadriceps. No difference in form-factors was found between the two limbs. Similar results were obtained with the anatomical method and significant correlations were obtained between the two methods. Quantitative analysis of muscle loss and recovery was possible by microCT after using a metallic contrast agent. Loss of bone secondary to muscle wastage induced by BTX and recovery showed a parallel evolution for bone and muscles.

Heat-induced osteonecrosis represents a simple, rapid, and inexpensive method for reproducing the effects of bone disease. In the present study, we employed this technique to induce osteonecrosis in femoral defects in rabbits and assessed the efficacy of treatment using Biphasic Calcium Phosphate (BCP) granules (MBCP+™, Biomatlante SA). After 3 weeks, the osteopromotion effects of BCP granules could be statistically proven ( P

International audience; Disuse induces a rapid bone loss in humans and animals; hypodynamia/sedentarity is now recognized as a risk factor for osteoporosis. Hypodynamia also decreases bone mass but its effects are largely unknown and only few animal models have been described. Hypodynamic chicken is recognized as a suitable model of bone loss but the effects on the quality have not been fully explored. We have used ten chickens bred in a large enclosure (FREE group); ten others were confined in small cages with little space to move around (HYPO group). They were sacrificed at 53 days and femurs were evaluated by microcomputed tomography (microCT) and nanoindentation. Sections (4µm thick) were analyzed by Fourier Transform InfraRed Microspectroscopy (FTIR) to see the effects on mineralization and collagen and quantitative backscattered electron imaging (qBEI) to image the mineral of the bone matrix. Trabecular bone volume and microarchitecture were significantly altered in the HYPO group. FTIR showed a significant reduction of the mineral-to-matrix ratio in the HYPO group associated with an increase in the carbonate content and an increase in crystallinity (calculated as the area ratio of subbands located at 1020 and 1030cm(-1)) indicating a poor quality of the mineral. Collagen maturity (calculated as the area ratio of subbands located at 1660 and 1690cm(-1)) was significantly reduced in the HYPO group. Reduced biomechanical properties were observed at the tissue level. Confined chicken represents a new model for the study of hypodynamia because bone changes are not created by a surgical lesion or a traumatic method. Animals have a reduced bone mass and present with an altered bone matrix quality which is less mineralized and whose collagen contains less crosslinks than in control chicken.

Calcium phosphate bioceramic granules associated with hydrosoluble polymers formed putties currently more used in clinical applications as they are easy to handle (injectability, moldability). In this study, 2 kinds of materials were tested in rabbit bone defects. The first one is InOss (Biomatlante), a microporous biphasic CaP granules (BCP, HA/TCP mixture) with polysaccharidic hydrogel; and the second one is Actifuse ABX (Baxter/Apatech), pure hydroxyapatite granules containing silicate (HA-Si) with blocks copolymer hydrogel (poloxamer), . The aim of this study was to compare osteogenic properties of two kinds of CaP putties containing HA-Si versus BCP and the kinetic of resorption of their hydrogel. Data have demonstrated that both hydrogels increase the handling properties. Bone regeneration was observed in the two types of sample, however at 3 weeks, Actifuse ABX hydrogel was not totally absorbed, while InOss hydrogel was no longer observed. The second difference observed was osteoconduction. Newly formed bone over the time period studied was moreover in close contact with BCP granules than with HA-Si granules. Larger granules resorption on time was observed for BCP compared to HA-Si. Resorption of Actifuse ABX remains limited and explains the faster kinetic of absorption for InOss. This study demonstrates biocompatibility, absorbability and bone ingrowth at the expense of the two types of putty injectable/moldable bioceramic used for bone regeneration.

It was demonstrated that microstructured surfaces improve cell spreading and bone ingrowth. Particularly, the surface roughness modulates the osseointegration of orthopaedic and dental implants. We have developed an innovative grit blasting process using Biphasic Calcium Phosphate, a Resorbable Biocompatible Blast Media (RBBM). PEEK is biocompatible but an inert material, involving no direct bone bonding. Implants coming from a rabbit experimental study, were processed for X-rays Micro tomography. Light microscopy and SEM were performed.It was demonstrated in this study that the surface treatment on PEEK improve the quality of bone architecture in direct contact with the sample surface, compared to the classical surface of PEEK. These data demonstrate that PEEK rough surface obtained by RBBM blasting maintain high biocompatibility and bone osteoconduction, and promote higher stability of the implant.

A new biphasic calcium phosphate ceramic material Hydros™ has been developed. The main attractive feature of BCP ceramic is their ability to form a strong direct bond with the host bone resulting in a strong interface. Currently, granules are more and more used in moldable, injectable bone substitutes. However, the biological behaviour of the particles can be influenced not only by chemical composition and crystallinity, but also by several parameters as microporosity and nano-micro sized particles. The aim of the study was to assess, in animal experiment,the role played by an Hydrated Putty Bioceramics (Hydros™), based on specific combination of hydrophilic micro and macrosized BCP particles, to obtain high osteogenic Injectable Bone Substitute. No sign of clinical rejection was noticed. In muscular area, no fibrous encapsulation was observed, degradation of the smaller particles is observed by macrophages and giant cells. At 12 weeks, more of 75% of BCP was resorbed. The biocompatibility and safety in human orthopaedic applications (tibial plateau fracture) has been demonstrated.

International audience; The objective of this study was to determine the effect of calcium phosphate mineral content on the bone in-growth at the expense of composite of co-polylactide polymer charged with 2 different ratios of β-TCP granules (10 and 24 w-% of β-TCP). The evaluation was realized in a long term rabbit bone model. After 24, 48 and 76 weeks, the implants were examined by micro CT, scanning electron microscopy (SEM) using backscattered electron (BSE) and light microscopy (polarized and blue light microscopy). No foreign body reaction was detected during the 76 weeks follow-up in any of the test samples. Polymer hydrolysis began at approximately 24 weeks, by 76 weeks, the pure polymer implant had begun to release P(96L/4D)LA particles and show signs of peripheral localized bone resorption. A decrease in the amount of CaP was noticed between 24 and 76 weeks in both 10wt-% and 24wt-% β-TCP/P(96L/4D)LA composites. The study showed that the highest bone in-growth was with 24 wt-% β-TCP/P(96L/4D)LA composite. Bone in-growth and mineralization were evident for the composites associated with specific peripheral bone architecture. Fluorescent labelling demonstrated high bone in-growth and remodeling at the interface, while for pure co-polymer no bone remodeling or bone activity was maintained after 48 weeks. The study demonstrated the positive effect of calcium phosphate content into P(96L/4D)LA. This kind of composite is a suitable resorbable osteoconductive matrix, which provides long term stability required for ligament fixation device.

β-Tricalcium phosphate (β-TCP) is a suitable biomaterial in oral and maxillofacial surgery since it can induce a rapid proliferation of woven bone. Granules, prepared by the polyurethane foam method, were implanted in critical size defects performed in the femoral condyles of New Zealand rabbits. Animals were studied after 8 and 28 days. Ketoprofen (a non-steroidal anti-inflammatory drug (NSAID)) was given for 8 and 28 days to evaluate its effects on the healing of the graft. Before euthanasia, the rabbits received an intravenous injection of fluorescent microbeads. Bones were analyzed by microcomputed tomography. β-TCP granules induced metaplastic bone trabeculae as early as 8 days post-surgery. At 28 days, the amount of bone was increased and the biomaterial volume decreased due to simultaneous macrophagic resorption. The amount of macrophages labeled with microbeads was less in the grafted area than in the vicinal intact marrow spaces. Ketoprofen had no effect on the amount of bone formed and on the number of labeled macrophages. The influence of small doses of NSAID, given in a short duration period, did not present deleterious effects on bone graft healing.

The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

An hydrated putty was prepared by mixing submicron particles, rounded particles and granules of Biphasic Calcium Phosphate (BCP) ceramics composed of HA and β-TCP phases. The material filled entirely critical sized defects in the femoral epiphysis of NZW rabbits. After 3, 6 and 12 weeks, histology revealed that submicron particles were rapidly degraded by multinucleated TRAP-positive cells. This osteoclastic resorption stimulated bone ingrowth while the large BCP particles served as scaffold supporting bone healing by osteoconduction.

Current resorbable membranes are generally from animal origin, like collagen, and are largely used in dentistry or orthopaedic for TGR (Tissue Guided Regeneration), in neurosurgery for Dura matter healing and others. Calcium alginates are generally used for wound dressing (external uses). The purpose of this study was to evaluate the osteogenic property of meshes realized with calcium alginate fibers. Membrane meshes were implanted in critical size defect of rabbit femoral epiphysis during 3 and 6 weeks. Micro CT and histological analysis demonstrated biocompatibility of calcium alginate meshes in bony area. Calcium alginate meshes have no osteogenic and osteoconductive properties, however calcium alginate meshes could be a good candidate for replacement of dacron balloon used in vertebroplasty.

The aim of this study was to evaluate the capacity of the association of calcium phosphate cement with collagen membrane for large segmental bone defect. Six adult beagle dog underwent defect creation in the ulna and was reconstructed with combination of macroporous calcium phosphate cement MCPC® and resorbable collagen membrane EZ Cure®. After 6 months of implantation, the samples were analyzed with Micro CT, light microscopy and SEM using BSE. Bridging of the defect with a lamellar and well organized bone was achieved in all animals. MCPC granules resorption was increased at the extremities of the implant. Collagen membrane at the expense of the implant was replaced by periosteum-like formation. The results demonstrate the ability of the composite to reconstruct large segmental and critical size defect in long bone.

We have developed a novel macroporous calcium phosphate cement MCPC® that sets to poorly crystalline apatite after mixing the powder component with an aqueous solution and has interconnective macroporosity We performed cranioplasty on rat model by injecting the new macroporous calcium phosphate cement MCPC®. The mechanical property of the cement is about 12MPa after 24 hours (compression test). The cement matrix is totally transformed into poorly crystalline apatite in 48 hours. This study demonstrates that MCPC® cement was suitable and efficient for parietal bone reconstruction. Its injectability and moldability allows to be used in bone reconstruction surgery and its mechanical properties are compatible to support calvarial reconstruction. In addition, a bone ingrowth onto the BCP granules occurred on time.

International audience; Bone substitutes are widely used for filling and restoring bone defects. Among them, methacrylic polymers are employed in load-bearing bones to seal hip prostheses. Incorporation of growth factors into a polymer device could be a way to enhance bone growth. In the present study, we evaluated the capacity of poly(2-hydroxyethyl methacrylate) – pHEMA – copolymerized with 2-vinyl pyrrolidone – VP – to release proteins. Fibroblast growth factor-2 (FGF-2) was incorporated into cylinders of p(HEMA-co-VP). FGF-2 release was studied by ELISA in vitro and cylinders were implanted in the femoral condyle of white New Zealand rabbits. After 2 months post-surgery, FGF-2 was able to enhance bone formation by increasing bone volume; this effect was evidenced by an increase in trabecular number and bone gain was mainly in the form of woven bone. At 3 months post-surgery, no difference could be evidenced between animals receiving vehicle or FGF-2. Animals receiving vehicle exhibited bone mass higher than at 2 months and woven bone was replaced by mature bone with a lamellar matrix. The hydrogel polymer allowed the release of FGF-2, which in return enhanced bone regeneration soon after surgery but the effect vanished rapidly.

Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.

Dedicated to Minimal Invasive Surgery MIS particularly in spine for vertebroplasty, the surgeons and radiologists ask for improvement of radio opacity, to be sure of the injection site, and to prevent injection in blood vessels. MBCP Gel® is an Injectible biomaterial non self hardening, the biomaterials consists of BCP granules associated with a hydrosoluble polymer. These materials have been shown to be perfectly biocompatible and potentially resorbable and, thanks to their initial plasticity, they assume the shape of the bone defects very easily, eliminating the need to shape the material to adjust to the implantation site. MBCP gels do not have mechanical properties like the hydraulic bone cements. However bone cells are able to invade the spaces created by the disappearance of the polymer carrier. Bone ingrowth takes place all around the granules at the expense of the resorption of the BCP granules. In time, the mechanical property is increased due to the presence of the newly formed bone. This study demonstrates an improvement of MBCP gel by freeze drying and reconstitution using iodine solution or sterile water in a classical model of rabbit bone defects.

The purpose of this study was to determine the effect of sintering conditions on microporosity of and cell proliferation and bone ingrowth on biphasic calcium phosphate (BCP) bioceramics. Discs were prepared from a calcium-deficient apatite preparation that upon sintering at 1050oC and above, results in a BCP with 60% hydroxyapatite (HA)/ 40% beta-tricalcium phosphate (β-TCP) ratio. The discs were divided into groups which were sintered under different conditions of heating rate (programmed vs. non-programmed) and temperature (1050°C vs. 1200°C). The discs were characterized in terms of composition (HA/β-TCP ratio), surface morphology, surface area, surface microporosity, per cent microporosity, and dissolution properties. The in vitro effect of sintering conditions on cell proliferation was determined using an established mouse fibroblast cell line (L929). Results demonstrated the following: (a) the HA/β-TCP ratio remained 60/40 regardless of sintering conditions; (b) the % microporosity, surface microporosity, surface area of the BCP and cell proliferation on the BCP significantly decreased with increasing sintering temperature, and (c) the extent of dissolution decreased with decreasing per cent microporosity. The in vivo study indicated no tissue adverse reaction and direct bone contact with the implant surface, confirming the biocompatibility of the BCP bioceramics. Resorption of the BCP and bone ingrowth was directly related to the sintering temperature: the higher the temperature, the lower the resorption and the bone ingrowth. Results of this study indicate that per cent microporosity of the BCP bioceramics affects its dissolution properties and cell response. The study demonstrates that optimum per cent microporosity elicits optimum cell response and should be considered to provide osteogenic/osteoinductive property to bioceramics.

We have performed and evaluated a composite combining PL DLLA and PCa able to have a better control of the hydrolysis and maintain of the mechanical property on time, until wound healing was achieved. Bioabsorbable osteoconductive composite is devoted to the development of resorbable osteosynthesis for spine and osteoarticular surgeries. Such resorbable osteosynthesis will be associated to new bone substitute having high osteogenic property but without initial mechanical property. The purpose of this study was to evaluate the resorption kinetic of a composite using PL DLLA (Poly [L-Lactide-co-D,L-Lactide] acide) charged with PCa granules and the interaction with injectable bioceramic without self hardening. MBCP gel® is a composite associating a mineral phase of an intimate nanoscale melting of hydroxyapatite and beta tri calcium phosphate and an aqueous phase containing a synthetic polymer derived from cellulose HPMC (hydroxyl propyl methyl cellulose).

Surface roughness modulates the osseointegration of orthopaedic and dental titanium implants. High surface roughness is currently obtained by blasting of titanium implants with silica or aluminium abrasive particles. This process includes into the surface abrasive particles and may cause the release of cytotoxic silica or aluminium ions in the peri implant tissue. To overcome this drawback, we currently develop an innovative gridblasting process using Biphasic Calcium Phosphate (BCP) particles (RBBM Resorbable and Biocompatible Blast Media) to generate biocompatible roughened titanium surface. This work present the technique of blasting using RBBM particles to provide a roughened surface which does not release cytotoxic elements and (ii) to assess the effects of such a roughened surface for bone osteointegration in critical size rabbit defect. Our results demonstrate that resorbable biphasic calcium phosphate abrasive particles can be used to create titanium surface roughness. This grid blasting process increases surface roughness of titanium implants and offers a non cytotoxic surface for rapid and efficient osteointegration.

We performed vertebroplasty on goat model by injecting a new macroporous calcium phosphate cement MCPC®. The mechanical property of the cement is about 12MPa after 24 hours (compression test). The cement matrix is totally transformed into poorly crystallized apatite in 48 hours. This study demonstrates that MCPC cement was suitable and efficient for a spine application. Its injectability allows to be used in mini invasive surgery and its mechanical properties are compatible to support spine strength. In addition, a bone ingrowth onto the BCP granules occurred with time.

Resorbable osteosynthesis based on PLLA and derivatives will be associated to bone substitute for bone reconstruction. We have performed rand evaluated a composite combining PL DLLA and Biphasic calcium phosphate able to have a), a better controlled hydrolysis in the purpose to preserve on time the mechanical property, and b), for long term efficiency, bone ingrowth at the expense of the osteosynthesis and the associated bone substitute. A new calcium phosphate cement MCPC® was tested with such composite. The novel macroporous calcium phosphate cement MCPC sets to poorly crystalline apatite after mixing the powder component and an aqueous solution. Interconnective macroporosity was induced on time by resorption of one part of the MCPC®. The multiphasic calcium phosphate components in the cement, are resorbed at different rates allowing the replacement by newly formed bone. This study reports the biocompatibility and the interactions of a composite using PL DLLA (Poly [L-Lactide-co-D,L-Lactide] acid) charged with biphasic calcium phosphate granules and a self setting calcium phosphate cement of new generation.

Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1–2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

Resume Affirmer avec certitude la fusion d’une arthrodese reste difficile malgre les progres des techniques d’imagerie. Le microscanner est une technique d’imagerie qui permet une analyse a la fois qualitative et quantitative de la micro-architecture osseuse. L’objectif de cette etude etait d’evaluer cette technique en l’appliquant a l’arthrodese cervicale avec cage inter-somatique sur un modele animal et de valider les resultats par une analyse histologique et en microscopie electronique a balayage. Huit chevres ont ete operees d’une discectomie au niveau C3-C4 et reparties en deux groupes. Le groupe 1 (3 animaux) a ete implante avec des cages en PEEK sans greffon osseux. Le groupe 2 (5 chevres) a ete implante avec la meme cage remplie d’os autologue iliaque. Apres euthanasie, au 6e mois, les niveaux instrumentes ont ete analyses au microscanner, puis sur coupe histologique et en microscopie electronique a balayage (MEB). Les 3 animaux implantes avec une cage vide (groupe 1) ont developpe une pseudarthrose, tandis qu’un seul animal presentait une pseudarthrose dans le groupe 2. Les analyses histologique et MEB ont confirme le diagnostic fait par microscanner. Le microscanner a, en outre, permis l’analyse en 3 dimensions de l’echantillon et l’etude de l’architecture trabeculaire du greffon inter-somatique. Le microscanner permet une analyse micrometrique d’un echantillon. Il represente la seule technique d’analyse en 3 dimensions (des coupes sont possible dans les trois plans de l’espace et la reconstruction 3D visualise l’ensemble de l’echantillon) a la fois qualitative et quantitative. L’analyse de la micro-architecture trabeculaire est un progres majeur dans l’evaluation de la valeur mecanique d’une arthrodese. Il s’agit de la seule technique non destructrice pour l’echantillon, qui reste utilisable pour d’autres tests en particulier biomecanique. Le microscanner represente une avancee technique pour l’analyse de la fusion osseuse. Les applications futures de cette technique quantitative seront vraisemblablement nombreuses (suivi d’une arthrodese, evaluation de la qualite mecanique d’une greffe…). Son adaptation in vivo sera vraisemblablement rapide.

Two porous titanium implants with interconnected pore size of 800 and 1200 m in diameter, were fabricated by a rapid prototyping method. Their dimensions and structure accomplished the expected design with accuracy and reproducibility. The porosity of titanium was around 60%. The compressive strength and Young’s modulus were comparable to those of cortical bone with values around 80 MPa and 2.7 GPa, respectively. The implants were implanted bilaterally in the femoral epiphysis of 12 New Zealand Rabbits. After 3 and 8 weeks, abundant bone formation was found in the titanium porous structure. This work demonstrates that macroporous titanium with controlled shape and porosity is a good candidate for orthopaedic and maxilofacial applications.

Our purpose was to evaluate the osteointegration of bilayered calcium phosphate (CaP)-coated femoral hip stems in a canine model. A first layer of hydroxyapatite (HA) 20 microm thick and a superficial layer of Biphasic Calcium Phosphate (BCP) 30 microm thick were plasma-sprayed on to the proximal region of sandblasted Ti6Al4V prostheses. Bilayered CaP-coated and non-coated canine femoral stems were implanted bilaterally under general anesthesia in 6 adult female Beagle dogs. After 6 and 12 months, a significant degradation of the bilayered coating occurred with a remainder of 33.1+/-12.4 and 23.6+/-9.2 microm in thickness, respectively. Lamellar bone apposition was observed on bilayered coated implants while fibrous tissue encapsulation was observed on non-coated femoral stems. The bone-implant contacts (BIC) were 91+/-3% and 81+/-8% for coated and 7+/-8% and 8+/-12% for non-coated implants, at 6 and 12 months, respectively. Our study supports the concept of a direct relationship between the biodegradation of CaP coating and the enhanced osteointegration of titanium prostheses. A bilayered CaP coating might therefore enhance bone apposition in the early stages because of the superior bioactivity of the BCP layer while the more stable HA layer might sustain bone bonding over long periods.

This in vivo study investigated the efficiency of an injectable calcium phosphate bone substitute (IBS) for bone regenerative procedures through non-destructive three-dimensional (3D) micro-tomographic (microCT) imaging, biomechanical testing with a non-destructive micro-indentation technique and 2D scanning electron microscopy (SEM) analysis. The injectable biomaterial was obtained by mixing a biphasic calcium phosphate (BCP) ceramic mineral phase and a cellulosic polymer. The BCP particles were 200-500 microm or 80-200 microm in diameter. The injectable material was implanted for 6 weeks into critical-sized bone defects at the distal end of rabbit femurs. Extensive new bone apposition was noted with both 2D and 3D techniques. Micro-CT showed that newly formed bone was in perfect continuity with the trabecular host bone structure and demonstrated the high interconnectivity of the restored bone network. For both IBS formulations, SEM and microCT gave very close measurements. The only detected significant difference concerned the amount of newly formed bone obtained with IBS 80-200 that appeared significantly higher with microCT analysis than with SEM (p=0.00007). Student t-tests did not show any significant difference in the amount of newly formed bone and remaining ceramic obtained from microCT analysis or SEM. Regression analysis showed satisfactory correlation between both the amount of newly formed bone and remaining ceramic obtained from microCT or SEM. For IBS 200-500, the newly formed bone rate inside the defect was 28.0+/-5.2% with SEM and yield strength of the samples was 18.8+/-5.4 MPa. For IBS 80-200, the newly formed bone rate inside the defect was 31.7+/-5.1% with SEM and yield strength of the samples was 26.8+/-4.5 MPa. Yield strength appeared well correlated with the amount of newly formed bone, specially observed with microCT. This study showed the ability of non-destructive techniques to investigate biological and mechanical aspects of bone replacement with injectable biomaterials.

Resume Les implants en titane sont devenus un traitement de choix pour les edentations totales ou partielles. La methode necessite cependant un double temps chirurgical et une mise en place de la prothese dentaire apres une phase de consolidation de 3 a 6 mois au cours de laquelle les patients conservent une mandibule edentee avec affleurement du sommet des implants au niveau de la gencive. La mise en charge immediate d’implants classiques est responsable de la survenue de micro-mouvements qui entrainent le descellement implantaire. De nouveaux designs d’implants permettent un ancrage immediat dans l’os, empechent les forces laterales de cisaillement et autorisent la mise en place de protheses precocement. Nous avons realise une etude experimentale chez le chien Beagle. Apres edentation partielle, deux types d’implants ont ete mis en place (implants a expansion et implants a clavettes). Au bout de 2 semaines, les implants ont ete recouverts d’une prothese or-palladium laissee en place pendant 12 semaines. Apres sacrifice, une etude par frequence de resonance (ISQ) et histomorphometrie a ete realisee. Les deux types d’implants etaient recouverts par la meme quantite d’os (volume et interface) sans interposition de tissu fibreux. Les implants a clavette presentaient une augmentation des parametres des stabilite ISQ superieure a celle des implants a expansion. Les implants a clavette, testes chez des chiens ayant une fonction masticatoire proche de l’homme, apparaissent interessants dans la mise en charge immediate par la prothese.

The aim of this study was to compare the bone colonization of a macroporous biphasic calcium phosphate (MBCP) ceramic in different sites (femur, tibia, and calvaria) in two animal species (rats and rabbits). A critical size defect model was used in all cases with implantation for 21 days. Bone colonization in the empty and MBCP-filled defects was measured with the use of backscattered electron microscopy (BSEM). In the empty cavities, bone healing remained on the edges, and did not bridge the critical size defects. Bone growth was observed in all the implantation sites in rats (approx. 13.6–36.6% of the total defect area, with ceramic ranging from 46.1 to 51.9%). The bone colonization appeared statistically higher in the femur of rabbits (48.5%) than in the tibia (12.6%) and calvaria (22.9%) sites. This slightly higher degree of bone healing was related to differences in the bone architecture of the implantation sites. Concerning the comparison between animal species, bone colonization appeared greater in rabbits than in rats for the femoral site (48.5% vs. 29.6%). For the other two sites (the tibia and calvaria), there was no statistically significant difference. The increased bone ingrowth observed in rabbit femurs might be due to the large bone surface area in contact with the MBCP ceramics. The femoral epiphysis of rabbits is therefore a favorable model for testing the bone-bonding capacity of materials, but a comparison with other implantation sites is subject to bias. This study shows that well-conducted and fully validated models with the use of small animals are essential in the development of new bone substitutes. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 72B: 69–78, 2005

Objectif L’immobilisation a long terme ou une exposition prolongee a la microgravite induisent une atrophie musculaire et une perte osseuse severe. La fonte musculaire qui accompagne la perte osseuse a ete peu etudiee principalement de par l’absence de methode d’analyse appropriee. L’objectif de l’etude est d’evaluer la fonte musculaire dans un modele d’immobilisation chez la souris en utilisant un agent de contraste specifique pour une analyse en microCT. Materiel et methodes 18 souris ont recu une injection de toxine botulique (BTX) dans le quadriceps pour induire une paralysie du membre posterieur droit ; le cote gauche correspond au temoin. Les souris ont ete sacrifiees a 7, 14, 21, 28, 56 et 90 jours post-BTX (3 souris/groupe). 56 et 90 jours correspondent a la recuperation de la mobilite. 3 souris ont ete sacrifiees a j0. Les membres posterieurs ont ete immerges dans une solution de chlorure de mercure (HgCl2) pour la visualisation 3D des muscles par microCT et une analyse morphometrique. Trois parametres ont ete calcules pour 3 muscles d’interet (le quadriceps femoral, le gastrocnemien et le plantaire) : l’aire (mm2) occupee par chaque muscle dans la section 2D, la circularite et l’aspect ratio. Le gastrocnemien et le quadriceps femoral ont ete disseques et peses. Resultats L’aire dans les membres paralyses est reduite des le 7e jour pour le gastrocnemien et le quadriceps. L’aire est minimale au 21e jour pour le quadriceps (–46,9 %) et au 28e jour pour le gastrocnemien (–47,9 %). Aucune difference dans les parametres geometriques de forme n’a ete trouvee. Aucune modification n’a ete observee pour le muscle plantaire. Des correlations significatives ont ete obtenues entre l’aire et le poids pour le gastrocnemien et le quadriceps. Conclusion L’utilisation d’un agent de contraste specifique ouvre de nouvelles perspectives pour mieux comprendre les relations musculosquelettiques.

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. (C) 2003 Wiley Periodicals, Inc.

A bilayered bioactive-gradient coating, consisting of a superficial layer of biphasic calcium phosphate (BCP) and a deep layer of hydroxyapatite (HA), promotes faster osseointegration and higher shear strength in non-loading conditions than do monolayer BCP or HA coatings. This study evaluated the biofunctionality of this coating in weight-bearing conditions at 6 and 12 months. The coating was plasma-sprayed on the metaphyseal portion of a sandblasted Ti6Al4V canine femoral prosthesis implanted using the surgical press-fit technique. An identical uncoated stem served as the control. Metaphyseal bone-to-implant apposition was increased for coated (∼90% and 80% respectively at 6 and 12 months) as compared to uncoated implant (∼7% at 6 and 12 months). Limited bone apposition was observed at the diaphyseal level. After 12 months, the uncoated implant interface consisted of well-organized, active fibrous tissue, whereas only inactive fibrous tissue interposition was observed at diaphyseal levels of the coated implant. At 6 months, the mineralization apposition rate (MAR) was similar, regardless of implant or bone structures. At 12 months, a significant decrease of MAR was observed around the uncoated implant. Transmission electron microscopy studies of the interface showed precipitation of biological apatite crystals in close association with mineralized collagenous bone matrix. Our results suggest a direct relationship between bioactivity and enhanced bone formation. The sandwich coating used is effective in promoting massive metaphyseal osseointegration, which ensures mechanical stability for early weight-bearing and should prevent long-term complications.

International audience; Disuse induces a rapid bone loss in adults; sedentarity is now recognized as a risk factor for osteoporosis. Hypoactivity or confinement also decrease bone mass in adults but their effects are largely unknown and only few animal models have been described. We have used 10 chickens of the rapidly growing strain 857K bred in a large enclosure (FREE group); 10 others were confined in small cages with little space to move around (HYPO group). They were sacrificed at 53 days and femurs and tibias were evaluated by texture analysis, dual energy X-ray densitometry, microcomputed tomography (microCT) and histomorphometry. Hypoactivity had no effect on the length and diameter of the bones. Bone mineral density (BMD), microCT (trabecular bone volume and trabecular microarchitecture) and texture analysis were always found significantly reduced in the animals of the HYPO group. BMD was reduced at both femur and tibia diaphysises; BMD of the metaphysis was significantly reduced in the femur but not in the tibia. An increase in osteoid volume and surfaces was noted in the HYPO group. However, there was no alteration of the mineral phase as the osteoid thickness did not differ from control animals. Bone loss was much more pronounced at the lower femur metaphysis than at the upper metaphysis of the tibia. At the tibia, only microarchitectural changes of trabecular bone could be evidenced. The confined chicken represents a new method for the study of hypodynamia since these animals do not have surgical lesions.

There is a large variety of commercial bioceramic bone substitutes; however, the prerequisites for bone reconstruction and tissue engineering are often absent in research and clinical applications. The main criteria for the use of bioceramics are easily handled biomaterials that are solid, injectable, and/or shapeable. Furthermore, the material must have the appropriate osteoconductive and osteoinductive properties. New bone regeneration technologies, such as “smart matrices,” must be developed and optimized to increase their suitability for bone defects and to support suitable Ortho Biology. This contribution presents the basic smart bone substitutes used for bone regeneration, which will support the twenty-first-century challenge in osteoarticular pathology to replace autografts with more efficient synthetic materials. The paper is focused on the specifications required for the smart matrix (or osteo instructive matrix), the needs of the surgeon, the clinical indications, the regulatory constraints, and product development and marketing. Finally, an example was presented of a smart matrix medical device developed and used in bone regeneration and details the cascade of steps necessary to put it on the market: research and development, meeting the regulatory criteria, preclinical and clinical data, CE mark approval, and FDA (United States Federal Drug Administration).

International audience; Multiple myeloma is due to the proliferation of malignant plasma cells which increase the number of osteoclasts leading to trabecular and cortical bone osteolysis. The 5T2MM murine model reproduces the human disease and microcomputed tomography is a precise tool to investigate bone loss. Bisphosphonates (zoledronic acid or pamidronate) are used in preventing osteolysis. However, loss of cortical bone in not possible to quantify by histomorphometry on histological sections or microCT images. Osteolysis was studied in mice grafted with the 5THL subline to see if one drug was more active after 10 weeks. Mice were distributed into 4 groups: control, untreated, treated with pamidronate or with zoledronic acid. The left femurs were embedded undecalcified and sectioned at 7 μm. The right tibias and femurs were analyzed by microCT and trabecular morphometric parameters were obtained. Cortical bone osteolysis was analyzed by developing a new algorithm to unwrap microCT sections of the cortices, allowing measurement of the number of perforations, porosity and mean perforation area. The bisphosphonates had no significant effect on the tumor growth as evidence by the absence of effect on the M-protein level. Cortical perforations were evidenced on histological sections and their number seemed to be reduced by both bisphosphonates. MicroCT was used to quantify the trabecular bone: a bone loss was evidenced in the untreated myeloma group and both bisphosphonates appeared equal to preserve trabecular mass. However, the number and size of cortical perforations cannot be determined on 3D models. Unwrapping microCT images provided flat images allowing a precise determination of cortical perforations. Pamidronate did not reduce the number and size of cortical perforations but significantly reduced porosity. Zoledronic acid appeared significantly superior and considerably reduced all parameters. Unwrapping microCT image is a new method allowing the measurement of cortical perforations in bone malignancies, a parameter that cannot be measured correctly on 2D histological sections.

International audience; 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.

Gene transfer in regenerating dog liver using high-titer recombinant retroviral vectors carrying the E. coli beta-galactosidase gene was studied. Supernatants containing amphotropic or gibbon ape pseudotyped recombinant retroviruses were infused into a peripheral vein in beagle dogs after partial hepatectomy. The kinetics of liver regeneration were determined in the animals and daily infusions were carried out for 4 or 5 days during the regeneration period. Up to 2.8% of hepatocytes were beta-galactosidase positive at the end of the procedure. However, the number of positive cells declined rapidly and few positive hepatocytes were detected after 3 weeks. PCR demonstrated the disappearance of the provirus. Histologically, inflammatory lesions were observed in the transduced livers. Finally, we demonstrated the presence of a cytotoxic T lymphocyte immune response directed against beta-galactosidase-expressing cells, which could explain the disappearance of the transgene. This work suggests that the efficiency of in vivo gene delivery using high-titer retroviral vectors directly infused into the circulation may be hampered by a cytotoxic immune response against the infected cells.

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.

9th European Meeting on Injectable Bone and Joint Substitution Materials, LAUSANNE, SWITZERLAND, MAR 01-02, 1999; This in vivo study investigated the influence of two calcium phosphate particle sizes (40-80 mu m and 200-500 mu m) 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, (Bone 25:71S-74S; 1999) (C) 1999 by Elsevier Science Inc, All rights reserved.

Two different preparations of biphasic calcium phosphate (BCP) were characterized in vitro: BCP1 from a mechanical mixture of hydroxyapatite (HA) and β-tricalcium phosphate (β-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