Bio

Bio


Originally from Nantes, France, I obtained my dental/specialty degrees and PhD from Paris University. After completing my graduate research in Montreal and Paris on pathological mineralization, I joined Stanford for a postdoctoral fellowship in implant dentistry. In the near future, I wish to conduct my own research in bone biology, along with a clinical activity in periodontics, either in France or in Israel.

Honors & Awards


  • Laureate, French Academy of Dental Surgery (2013)
  • Young Investigator Award, International Conference on the Chemistry and Biology of Mineralized Tissues (2013)
  • Ethics Award, French College of Dentists (2011)

Boards, Advisory Committees, Professional Organizations


  • Scientific advisory board member, Journal de Parodontologie et d’Implantologie Orale (2017 - Present)

Professional Education


  • Post-doctoral Fellowship, Stanford University, Plastic and Reconstructive Surgery (2019)
  • PhD, Paris Descartes University, Pathophysiology (2017)
  • Specialty Certificate, European Federation of Periodontology/Paris Diderot University, Periodontology, Periodontics and Implant Dentistry (2017)
  • DDS, Paris Descartes University, Dentistry (2012)
  • MSc, Paris Diderot University, Periodontology (2014)
  • MSc, Paris Descartes University, Biomineralization (2012)

Stanford Advisors


Publications

All Publications


  • A Novel Osteotomy Preparation Technique to Preserve Implant Site Viability and Enhance Osteogenesis. Journal of clinical medicine Chen, C. H., Coyac, B. R., Arioka, M., Leahy, B., Tulu, U. S., Aghvami, M., Holst, S., Hoffmann, W., Quarry, A., Bahat, O., Salmon, B., Brunski, J. B., Helms, J. A. 2019; 8 (2)

    Abstract

    The preservation of bone viability at an osteotomy site is a critical variable for subsequent implant osseointegration. Recent biomechanical studies evaluating the consequences of site preparation led us to rethink the design of bone-cutting drills, especially those intended for implant site preparation. We present here a novel drill design that is designed to efficiently cut bone at a very low rotational velocity, obviating the need for irrigation as a coolant. The low-speed cutting produces little heat and, consequently, osteocyte viability is maintained. The lack of irrigation, coupled with the unique design of the cutting flutes, channels into the osteotomy autologous bone chips and osseous coagulum that have inherent osteogenic potential. Collectively, these features result in robust, new bone formation at rates significantly faster than those observed with conventional drilling protocols. These preclinical data have practical implications for the clinical preparation of osteotomies and alveolar bone reconstructive surgeries.

    View details for PubMedID 30717291

  • Periodontal reconstruction by heparan sulfate mimetic-based matrix therapy in Porphyromonas gingivalis-infected mice. Heliyon Coyac, B. R., Detzen, L., Doucet, P., Baroukh, B., Llorens, A., Bonnaure-Mallet, M., Gosset, M., Barritault, D., Colombier, M. L., Saffar, J. L. 2018; 4 (8): e00719

    Abstract

    Periodontitis is a set of chronic inflammatory diseases affecting the supporting structures of the teeth, during which a persistent release of lytic enzymes and inflammatory mediators causes a self-perpetuating vicious cycle of tissue destruction and repair. A matrix-based therapy using a heparan sulfate (HS) analogue called ReGeneraTing Agent (RGTA) replaces destroyed HS by binding to available heparin-binding sites of structural molecules, leading to restoration of tissue homeostasis in several inflammatory tissue injuries, including a hamster periodontitis model.The ability of RGTA to restore the periodontium was tested in a model of Porphyromonas gingivalis-infected Balb/cByJ mice. After 12 weeks of disease induction, mice were treated weekly with saline or RGTA (1.5 mg/kg) for 8 weeks. Data were analyzed by histomorphometry.RGTA treatment restored macroscopic bone loss. This was related to (1) a significant reduction in gingival inflammation assessed by a decrease in infiltrated connective tissue, particularly in cells expressing interleukin 1ß, an inflammatory mediator selected as a marker of inflammation; (2) a normalization of bone resorption parameters, i.e. number, activation and activity of osteoclasts, and number of preosteoclasts; (3) a powerful bone formation reaction. The Sharpey's fibers of the periodontal ligament recovered their alkaline phosphatase coating. This was obtained while P. gingivalis infection was maintained throughout the treatment period.RGTA treatment was able to control the chronic inflammation characteristic of periodontitis and blocked destruction of periodontal structures. It ensured tissue regeneration with recovery of the periodontium's anatomy.

    View details for DOI 10.1016/j.heliyon.2018.e00719

    View details for PubMedID 30101201

    View details for PubMedCentralID PMC6083019

  • Impaired mineral quality in dentin in X-linked hypophosphatemia. Connective tissue research Coyac, B. R., Falgayrac, G., Penel, G., Schmitt, A., Schinke, T., Linglart, A., McKee, M. D., Chaussain, C., Bardet, C. 2018; 59 (sup1): 91–96

    Abstract

    X-linked hypophosphatemia (XLH) is a skeletal disorder arising from mutations in the PHEX gene, transmitted in most cases as an X-linked dominant trait. PHEX deficiency leads to renal phosphate wasting and hypophosphatemia, as well as impaired mineralization of bone and dentin, resulting in severe skeletal and dental complications. Dentin mineralization defects appear as characteristic, large interglobular spaces resulting from the lack of fusion of calculospherites in the circumpulpal region during the mineralization process. Here, we examined changes in the composition and structure of dentin using Raman spectroscopy on XLH human teeth, and using transmission electron microscopy on the dentin of Hyp mice (the murine model of XLH). The dentin of patients with XLH showed changes in the quality of the apatitic mineral, with greater carbonate substitution and lower crystallinity compared to the dentin of age-matched control teeth. In addition, ultrastructural analysis by transmission electron microscopy revealed a major disorganization of the peri- and intertubular structure of the dentin, with odontoblast processes residing within an unmineralized matrix sheath in the Hyp mouse. Taken together, these results indicate that like for bone and tooth cementum, there are impaired mineral quality and matrix changes in XLH dentin reflecting high sensitivity to systemic serum phosphate levels and possibly other local changes in the dentin matrix.

    View details for DOI 10.1080/03008207.2017.1417989

    View details for PubMedID 29745817

  • Defective Mineralization in X-linked Hypophosphatemia Dental Pulp Cell Cultures JOURNAL OF DENTAL RESEARCH Coyac, B. R., Hoac, B., Falgayrac, G., Chafey, P., Slimani, L., Rowe, P. S., Penel, G., Linglart, A., McKee, M. D., Chaussain, C., Bardet, C. 2017

    View details for DOI 10.1177/0022034517728497

  • Tissue-specific mineralization defects in the periodontium of the Hyp mouse model of X-linked hypophosphatemia. BONE Coyac, B. R., Falgayrac, G., Baroukh, B., Slimani, L., Sadoine, J., Penel, G., Biosse-Duplan, M., Schinke, T., Linglart, A., McKee, M. D., Chaussain, C., Bardet, C. 2017
  • Mineralization of Dense Collagen Hydrogel Scaffolds by Human Pulp Cells JOURNAL OF DENTAL RESEARCH Coyac, B. R., Chicatun, F., Hoac, B., Nelea, V., Chaussain, C., Nazhat, S. N., McKee, M. D. 2013; 92 (7): 648-654

    Abstract

    While advances in biomineralization have been made in recent years, unanswered questions persist on bone- and tooth-cell differentiation, on outside-in signaling from the extracellular matrix, and on the link between protein expression and mineral deposition. In the present study, we validate the use of a bioengineered three-dimensional (3D) dense collagen hydrogel scaffold as a cell-culture model to explore these questions. Dental pulp progenitor/stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into an extracellular matrix-like collagen gel whose fibrillar density was increased through plastic compression. SHED viability, morphology, and metabolic activity, as well as scaffold mineralization, were investigated over 24 days in culture. Additionally, measurements of alkaline phosphatase enzymatic activity, together with immunoblotting for mineralized tissue cell markers ALPL (tissue-non-specific alkaline phosphatase), DMP1 (dentin matrix protein 1), and OPN (osteopontin), demonstrated osteo/odontogenic cell differentiation in the dense collagen scaffolds coincident with mineralization. Analyses of the mineral phase by electron microscopy, including electron diffraction and energy-dispersive x-ray spectroscopy, combined with Fourier-transform infrared spectroscopy and biochemical analyses, were consistent with the formation of apatitic mineral that was frequently aligned along collagen fibrils. In conclusion, use of a 3D dense collagen scaffold promoted SHED osteo/odontogenic cell differentiation and mineralization.

    View details for DOI 10.1177/0022034513488599

    View details for Web of Science ID 000320432100013

    View details for PubMedID 23632809

  • Phosphate and Vitamin D Prevent Periodontitis in X-Linked Hypophosphatemia JOURNAL OF DENTAL RESEARCH Duplan, M. B., Coyac, B. R., Bardet, C., Zadikian, C., ROTHENBUHLER, A., Kamenicky, P., Briot, K., Linglart, A., Chaussain, C. 2017; 96 (4): 388-395
  • Osteoporitin and the dento-osseous pathobiology of X-linked hypophosphatemia BONE Boukpessi, T., Hoac, B., Coyac, B. R., Leger, T., Garcia, C., Wicart, P., Whyte, M. P., Glorieux, F. H., Linglart, A., Chaussain, C., McKee, M. D. 2017; 95: 151-161

    Abstract

    Seven young patients with X-linked hypophosphatemia (XLH, having inactivating PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of defective bone mineralization near osteocytes - the so-called hallmark periosteocytic (lacunar) "halos" of XLH. OPN was also localized in the pericanalicular matrix extending beyond the osteocyte lacunae, as well as in the hypomineralized matrix of tooth dentin. OPN, a potent inhibitor of mineralization normally degraded by PHEX, is a member of a family of acidic, phosphorylated, calcium-binding, extracellular matrix proteins known to regulate dental, skeletal, and pathologic mineralization. Associated with the increased amount of OPN (along with inhibitory OPN peptide fragments) in XLH bone matrix, we found an enlarged, hypomineralized, lacuno-canalicular network - a defective pattern of skeletal mineralization that decreases stiffness locally at: i) the cell-matrix interface in the pericellular environment of the mechanosensing osteocyte, and ii) the osteocyte's dendritic network of cell processes extending throughout the bone. Our findings of an excess of inhibitory OPN near osteocytes and their cell processes, and in dentin, spatially correlates with the defective mineralization observed at these sites in the skeleton and teeth of XLH patients. These changes likely contribute to the dento-osseous pathobiology of XLH, and participate in the aberrant bone adaptation and remodeling seen in XLH.

    View details for DOI 10.1016/j.bone.2016.11.019

    View details for Web of Science ID 000392165100020

    View details for PubMedID 27884786

  • Accelerated craniofacial bone regeneration through dense collagen gel scaffolds seeded with dental pulp stem cells SCIENTIFIC REPORTS Chamieh, F., Collignon, A., Coyac, B. R., Lesieur, J., Ribes, S., Sadoine, J., Llorens, A., Nicoletti, A., Letourneur, D., Colombier, M., Nazhat, S. N., Bouchard, P., Chaussain, C., Rochefort, G. Y. 2016; 6

    Abstract

    Therapies using mesenchymal stem cell (MSC) seeded scaffolds may be applicable to various fields of regenerative medicine, including craniomaxillofacial surgery. Plastic compression of collagen scaffolds seeded with MSC has been shown to enhance the osteogenic differentiation of MSC as it increases the collagen fibrillary density. The aim of the present study was to evaluate the osteogenic effects of dense collagen gel scaffolds seeded with mesenchymal dental pulp stem cells (DPSC) on bone regeneration in a rat critical-size calvarial defect model. Two symmetrical full-thickness defects were created (5 mm diameter) and filled with either a rat DPSC-containing dense collagen gel scaffold (n = 15), or an acellular scaffold (n = 15). Animals were imaged in vivo by microcomputer tomography (Micro-CT) once a week during 5 weeks, whereas some animals were sacrificed each week for histology and histomorphometry analysis. Bone mineral density and bone micro-architectural parameters were significantly increased when DPSC-seeded scaffolds were used. Histological and histomorphometrical data also revealed significant increases in fibrous connective and mineralized tissue volume when DPSC-seeded scaffolds were used, associated with expression of type I collagen, osteoblast-associated alkaline phosphatase and osteoclastic-related tartrate-resistant acid phosphatase. Results demonstrate the potential of DPSC-loaded-dense collagen gel scaffolds to benefit of bone healing process.

    View details for DOI 10.1038/srep38814

    View details for Web of Science ID 000389570500001

    View details for PubMedID 27934940

    View details for PubMedCentralID PMC5146967

  • Abnormal osteopontin and matrix extracellular phosphoglycoprotein localization, and odontoblast differentiation, in X-linked hypophosphatemic teeth CONNECTIVE TISSUE RESEARCH Salmon, B., Bardet, C., Coyac, B. R., Baroukh, B., Naji, J., Rowe, P. S., Vital, S. O., Linglart, A., McKee, M. D., Chaussain, C. 2014; 55: 79-82

    Abstract

    Mutations in phosphate-regulating gene (PHEX) lead to X-linked hypophosphatemic rickets (XLH), a genetic disease characterized by impaired mineralization in bones and teeth. In human XLH tooth dentin, calcospherites that would normally merge as part of the mineralization process are separated by unmineralized interglobular spaces where fragments of matrix proteins accumulate. Here, we immunolocalized osteopontin (OPN) in human XLH teeth, in a three-dimensional XLH human dental pulp stem cell-collagen scaffold culture model and in a rat tooth injury repair model treated with acidic serine- and aspartate-rich motif peptides (ASARM). In parallel, matrix extracellular phosphoglycoprotein (MEPE) immunolocalization and alkaline phosphatase (ALP) activity were assessed in XLH teeth. OPN was expressed by odontoblasts in the XLH models, and localized to the abnormal calcospherites of XLH tooth dentin. In addition, ALP activity and MEPE localization were abnormal in human XLH teeth, with MEPE showing an accumulation in the unmineralized interglobular spaces in dentin. Furthermore, XLH odontoblasts failed to form a well-polarized odontoblast layer. These data suggest that both MEPE and OPN are involved in impaired tooth mineralization associated with XLH, possibly through different effects on the mineralization process.

    View details for DOI 10.3109/03008207.2014.923864

    View details for Web of Science ID 000341231000018

    View details for PubMedID 25158186

  • MEPE-Derived ASARM Peptide Inhibits Odontogenic Differentiation of Dental Pulp Stem Cells and Impairs Mineralization in Tooth Models of X-Linked Hypophosphatemia PLOS ONE Salmon, B., Bardet, C., Khaddam, M., Naji, J., Coyac, B. R., Baroukh, B., Letourneur, F., Lesieur, J., Decup, F., Le Denmat, D., Nicoletti, A., Poliard, A., Rowe, P. S., Huet, E., Vital, S. O., Linglart, A., McKee, M. D., Chaussain, C. 2013; 8 (2)

    Abstract

    Mutations in PHEX (phosphate-regulating gene with homologies to endopeptidases on the X-chromosome) cause X-linked familial hypophosphatemic rickets (XLH), a disorder having severe bone and tooth dentin mineralization defects. The absence of functional PHEX leads to abnormal accumulation of ASARM (acidic serine- and aspartate-rich motif) peptide - a substrate for PHEX and a strong inhibitor of mineralization - derived from MEPE (matrix extracellular phosphoglycoprotein) and other matrix proteins. MEPE-derived ASARM peptide accumulates in tooth dentin of XLH patients where it may impair dentinogenesis. Here, we investigated the effects of ASARM peptides in vitro and in vivo on odontoblast differentiation and matrix mineralization. Dental pulp stem cells from human exfoliated deciduous teeth (SHEDs) were seeded into a 3D collagen scaffold, and induced towards odontogenic differentiation. Cultures were treated with synthetic ASARM peptides (phosphorylated and nonphosphorylated) derived from the human MEPE sequence. Phosphorylated ASARM peptide inhibited SHED differentiation in vitro, with no mineralized nodule formation, decreased odontoblast marker expression, and upregulated MEPE expression. Phosphorylated ASARM peptide implanted in a rat molar pulp injury model impaired reparative dentin formation and mineralization, with increased MEPE immunohistochemical staining. In conclusion, using complementary models to study tooth dentin defects observed in XLH, we demonstrate that the MEPE-derived ASARM peptide inhibits both odontogenic differentiation and matrix mineralization, while increasing MEPE expression. These results contribute to a partial mechanistic explanation of XLH pathogenesis: direct inhibition of mineralization by ASARM peptide leads to the mineralization defects in XLH teeth. This process appears to be positively reinforced by the increased MEPE expression induced by ASARM. The MEPE-ASARM system can therefore be considered as a potential therapeutic target.

    View details for DOI 10.1371/journal.pone.0056749

    View details for Web of Science ID 000316658800032

    View details for PubMedID 23451077

    View details for PubMedCentralID PMC3579870