Jean-Michel BOULER | Université de Nantes (original) (raw)

Papers by Jean-Michel BOULER

Journal of Inorganic Biochemistry, 1993

Two different preparations of biphasic calcium phosphate (BCP) were characterized in vitro: BCP 1... more Two different preparations of biphasic calcium phosphate (BCP) were characterized in vitro: BCP 1 from a mechanical mixture of hydroxyapatite (HA) and b-tricalcium phosphate (b-TCP) powders, and BCP 2 from calcination of a calcium-de®cient apatite (CDA). The structural, physicochemical and mechanical parameters of these two preparations were investigated, and two different macroporous BCP 1 MBCP 1 and BCP 2 MBCP 2 implants were manufactured and implanted in rabbit bone for in vivo bioactivity studies. Scanning electron microscopy observations showed that MBCP 1 implants had a signi®cantly higher degradation rate P 50X0001 than MBCP 2 implants. This was probably caused by the presence of calcium oxide impurities in BCP 1 and the more intimate mixture and stable ultrastructure of BCP 2. No signi®cant difference about the newly formed bone rate in these two BCP preparations was observed. Very slight variations in sintering conditions appeared to in¯uence the biodegradation behavior of the two MBCP implants despite their identical HA/b-TCP ratios and similar porosity. Precise and complete in vitro characterization enabled us to understand and predict in vivo degradation behavior.

Although initial results were promising for an injectable bone substitute (IBS) associating a hyd... more Although initial results were promising for an injectable bone substitute (IBS) associating a hydroxypropyl methylcellulose (HPMC) polymer vector (Benecel, 2 w/w %) with biphasic calcium phosphate (BCP), a sensitization reaction occurred probably related to the degree of polymer purity. In this context, Benecel and another HPMC, E4M were investigated in the present study. The expected composition of the polymers was confirmed by gas-liquid chromatography. Studies in the guinea pig showed that Benecel has strong sensitization capacity and E4M none. Benecel manifests impurities (30 times more than E4M) in individual fibers or rounded clumps that are apparently responsible for extreme sensitization. Purification by ultracentrifugation associated with 0.2 microm filtration can decrease sensitization capacity considerably, though with a slight loss of polymer concentration. Fourier transform infrared (FTIR) analysis showed that the impurities were largely cellulose derivatives. However, extraction by organic solvent, followed by FTIR studies and micro-X analysis, detected an oily substance containing carbon and silicon associated with the cellulose derivatives. E4M, a polymer with no sensitization capacity, could replace Benecel and improve results with IBS.

$Research paper thumbnail of Exploring relationships between fractal dimension and trabecular bone characteristics$

Progress in Biomedical Optics and Imaging - Proceedings of SPIE, 2012

ABSTRACT Bone microarchitecture is the predictor of bone quality or bone disease. It can only be ... more ABSTRACT Bone microarchitecture is the predictor of bone quality or bone disease. It can only be measured on a bone biopsy, which is invasive and not available for all clinical situations. Texture analysis on radiographs is a common way to investigate bone microarchitecture. But relationships between three-dimension histomorphometric parameters and two-dimension texture parameters are not always well known, with poor results. The aim of this paper is twofold : to study one classical parameter namely the fractal dimension which is easily computed on the 2D binary texture and to explore its relationships with the microarchitecture. We performed several experiments in order to check from ground truth the different possible values and their possible explanations. The results show great variations of the fractal dimension according to the size of the window and its location. These variations can be explained both by a misuse of the algorithm and by the number of trabecular and their characteristics inside the window where the fractal dimension is computed. This study also shows a specific interest to work with dual fractal dimension of the bone-spongious tissues.

Bone, 1999

Calcium phosphate materials have been increasingly employed in orthopedic and dental applications... more 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.

Different implant shapes have been proposed in the past years, as well as cemented implants and c... more Different implant shapes have been proposed in the past years, as well as cemented implants and custom-shaped implants. However, the lifespan has not yet been improved enough to respond to the clinical use of implants for young patients. The principal cause of THR failures is aseptic loosening, often observed associated with peri-implant osteolysis. Implants failure rate is strongly related to the short-term quality of fixation. Our work is based on the hypothesis that implants releasing bisphosphonate molecules from their coating would protect the nearby bone from early osteolysis and therefore show an improved fixation.

The present invention relates to a composition useful as bone substitute material comprising at l... more The present invention relates to a composition useful as bone substitute material comprising at least one calcium phosphate compound that is associated with pain medication. In addition, the present invention comprises a kit comprising a drug combination unit and obtained therefrom manufacturing process of a drug combined device comprising the production step of the composition, the composition, the composition and self-generated in the iliac Ling by graft collected use as the use of for the preparation of a drug useful in combination apparatus to fill bone defect portion and the composition, the composition of the support for tissue engineering, and relates to the use of compositions for the manufacture of a tooth or a bone implant.

The journal of pain : official journal of the American Pain Society, Jan 15, 2018

Postoperative pain after bone reconstruction is a serious complication that could jeopardize the ... more Postoperative pain after bone reconstruction is a serious complication that could jeopardize the global success of a surgery. This pain must be controlled and minimized during the first 3 to 4 postoperative days to prevent it from becoming chronic. In this study, a critical-size bone defect was created at the femoral distal end of rats and filled by an injectable calcium phosphate cement (CPC) loaded or not with local anesthetics (bupivacaine or ropivacaine). A functional evaluation of the gait was performed using the CatWalk system to compare the postoperative pain relief enhanced by the different CPCs after such a bone filling surgery. The results demonstrated significant pain relief during the short-term postoperative period, as shown by the print area and intensity parameters of the operated paw. At 24hours, the print area decreased by 65%, 42%, and 24%, and the intensity decreased by 25%, 9%, and 1% for unloaded, ropivacaine-loaded, and bupivacaine-loaded CPCs, respectively, co...

Drug discovery today, Jan 26, 2018

Management of postoperative pain following bone surgery includes administration of local anesthet... more Management of postoperative pain following bone surgery includes administration of local anesthetics (LAs). Smart delivery systems, including triggered systems, have been designed to provide a continuous release of LA in situ. However, these systems can provide a high level of LA locally. This review will examine the state-of-the-art regarding the LA delivery systems optimized for management of postoperative pain in bone surgery and will discuss the potential adverse effects of LAs on the overall pathways of bone healing, including the inflammation response phase, hemostasis phase, tissue repair phase and remodeling phase. There is a clinical need to document these effects and the potential impacts on the clinical outcome of the patient.

Journal of biomedical materials research. Part A, 2018

We previously reported that biphasic calcium phosphate (BCP) microparticles embedded in a blood c... more We previously reported that biphasic calcium phosphate (BCP) microparticles embedded in a blood clot induces ectopic bone formation in mice and repairs a critical femoral defect in rat. The present pilot study aimed to evaluate in dog and in two models of large defects the efficacy of this composite named "blood for reconstruction of bone" (BRB). We show here that BRB is a cohesive biomaterial easy to prepare from dog autologous blood and to mold to fill large bone defects. First in a model of cylindrical femoral condyle defect, the BRB was compared with BCP particles alone. After 8 weeks, this revealed that the amount of mature bone was slightly and significantly higher with BRB than with BCP particles. Second, in a model consisting in a 2 cm-long critical interruptive defect of the ulna, the BRB was compared with autologous bone. After 6 months, we observed that implantation of BRB can induce the complete reconstruction of the defect and that newly formed bone exhibits h...

Acta Biomaterialia

Two commercial formulations of apatitic calcium phosphate cements (CPCs), Graftys® Quickset (QS) ... more Two commercial formulations of apatitic calcium phosphate cements (CPCs), Graftys® Quickset (QS) and Graftys® HBS (HBS), similar in composition but with different initial setting time (7 and 15min, respectively), were combined to ovine whole blood. Surprisingly, although a very cohesive paste was obtained after a few minutes, the setting time of the HBS/blood composite dramatically delayed when compared to its QS analogue and the two blood-free references. Using solid state NMR, scanning electron microscopy and high frequency impedance measurements, it was shown that, in the particular case of the HBS/blood composite, formation of a reticulated and porous organic network occurred in the intergranular space, prior to the precipitation of apatite crystals driven by the cement setting process. The resulting microstructure conferred unique biological properties to this material upon implantation in bone defects, since its degradation rate after 4 and 12weeks was more than twice that for the three other CPCs, with a significant replacement by newly formed bone. A major challenge in the design of bone graft substitutes is the development of injectable, cohesive, resorbable and self-setting calcium phosphate cement (CPC) that enables rapid cell invasion with initial mechanical properties as close as bone ones. Thus, we describe specific conditions in CPC-blood composites where the formation of a 3D clot-like network can interact with the precipitated apatite crystals formed during the cement setting process. The resulting microstructure appears more ductile at short-term and more sensitive to biological degradation which finally promotes new bone formation. This important and original paper reports the design and in-depth chemical and physical characterization of this groundbreaking technology.

Journal of tissue engineering and regenerative medicine, Jan 12, 2017

Calcium phosphate (CaP)-based biomaterials are commonly used in bone reconstructive surgery to re... more Calcium phosphate (CaP)-based biomaterials are commonly used in bone reconstructive surgery to replace the damaged tissue, and can also serve as vectors for local drug delivery. Due to its inhibitory action on osteoclasts, the semi-metallic element gallium (Ga) is used for the systemic treatment of disorders associated with accelerated bone resorption. As it was demonstrated that Ga could be incorporated in the structure of CaP biomaterials, we investigated the biological properties of Ga-loaded CaP biomaterials. Culturing bone cells on Ga-CaP, we observed a decrease in osteoclast number and a downregulation of late osteoclastic markers expression, while Ga-CaP upregulated the expression of osteoblastic marker genes involved in the maturation of bone matrix. We next investigated in vivo bone reconstructive properties of different Ga-loaded biomaterials using a murine bone defect healing model. All implanted biomaterials showed a good osseointegration into the surrounding host tissue...

Journal of clinical and experimental dentistry, 2017

There are different mouthwashes containing chlorhexidine in different concentrations, as well as ... more There are different mouthwashes containing chlorhexidine in different concentrations, as well as various excipients. Chlorhexidine induce stains or discoloration in teeth and mucous membranes. The aim of this work was to design a model to reproduce in vitro staining associated with the use of different mouthwashes containing chlorhexidine. We used as substrates of natural teeth and elephant ivory slices. Different incubation baths were conducted over 21 days in culture dishes at 37°C. At the beginning of experiment before incubation (D0) and after 21 days (D21) of incubation with different mouthwashes, pictures of substrates were taken in a standardized manner and an image analysis software was used to analyse and quantify the staining under the various conditions by using the 3 main colours (Red, Green, Blue, RGB). The results of this work demonstrate a very good reproducibility of the protocol, and secondly, a different expression statistically significant of the primary blue colo...

Acta biomaterialia, Jan 17, 2017

Interaction of host blood with biomaterials is the first event occurring after implantation in a ... more Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP ...

Biochemical Pharmacology, 2016

Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoc... more Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoclastic activity. On the other hand, the semi-metallic element gallium (Ga) displays an inhibitory action on osteoclasts, and therefore on bone resorption, as well as antitumour properties. Thus, we explored in vitro Ga effects on osteoclastogenesis in an aggressive bone metastatic environment based on the culture of pre-osteoclast RAW 264.7 cells with conditioned medium from metastatic breast tumour cells, i.e. the breast tumour cell line model MDA-MB-231 and its bone-seeking clone MDA-231BO. We first observed that Ga dose-dependently inhibited the tumour cells-induced osteoclastic differentiation of RAW 264.7 cells. To mimic a more aggressive environment where pro-tumourigenic factors are released from bone matrix due to osteoclastic resorption, metastatic breast tumour cells were stimulated with TGF-β, a mayor cytokine in bone metastasis vicious cycle. In these conditions, we observed that Ga still inhibited cancer cells-driven osteoclastogenesis. Lastly, we evidenced that Ga affected directly and strongly the proliferation/viability of both cancer cell lines, as well as the expression of major osteolytic factors in MDA-231BO cells. With the exception of two small scale clinical studies from 1980s, this is the first time that antitumour properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for the local treatment of bone metastases in patients with breast cancer.

Acta biomaterialia, Jan 26, 2015

In this study, we propose a simple and effective strategy to prepare injectable macroporous calci... more In this study, we propose a simple and effective strategy to prepare injectable macroporous calcium phosphate cements (CPCs) by syringe-foaming via hydrophilic viscous polymeric solution, such as using silanized-hydroxypropyl methylcellulose (Si-HPMC) as a foaming agent. The Si-HPMC foamed CPCs demonstrate excellent handling properties such as injectability and cohesion. After hardening the foamed CPCs possess hierarchical macropores and their mechanical properties (Young's modulus and compressive strength) are comparable to those of cancellous bone. Moreover, a preliminary in vivo study in the distal femoral sites of rabbits was conducted to evaluate the biofunctionality of this injectable macroporous CPC. The evidence of newly formed bone in the central zone of implantation site indicates the feasibility and effectiveness of this foaming strategy that will have to be optimized by further extensive animal experiments.

Biomaterials Applications for Nanomedicine, 2011

Using a Calcium-Deficient Apatite as a Drug-Delivery System 189 Femoral trepanation using a biops... more Using a Calcium-Deficient Apatite as a Drug-Delivery System 189 Femoral trepanation using a biopsy needle was followed by injection of 1 mL of 10 9 colonyforming units (CFU)/mL S. aureus suspension directly into the knee cavity. Using this protocol, bacterial densities approached 9-log 10 CFU/g infected tissue 3 days post-infection that persisted at least 14 days without treatment. Unlike chronic models of osteomyelitis, no spontaneous recovery of the bacterial infection was observed. Moreover, the rabbit long bone model is appropriate for the study of osteomyelitis because rabbits are more prone to infection than other animals, such as rats. The size of New Zealand white rabbits makes it possible to more closely mimic human surgical procedures such as bone debridement and computer-controlled pharmacokinetic. Fig. 2. The acute experimental osteomyelitis rabbit model (Gaudin et al., 2011) 3. Calcium phosphate as a matrix of antibiotic release

Magnetic Resonance in Colloid and Interface Science, 2002