Aix-en-Provence, France
Aix-en-Provence, France

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Verron E.,French Institute of Health and Medical Research | Verron E.,Graftys Inc. | Gauthier O.,French Institute of Health and Medical Research | Gauthier O.,British Petroleum | And 6 more authors.
Biomaterials | Year: 2010

Resorbable calcium phosphate (CaP) biomaterials have demonstrated considerable efficacy in bone reconstructive surgery. Furthermore, bisphosphonates (BPs) are well known anti-resorptive agents largely used in clinical treatments for osteoporosis. An injectable BP-combined CaP matrix has been developed in order to biologically reinforce osteoporotic bone by increasing the bone fraction and improving bone micro-architecture. Our previous in vitro studies have shown that CaP is effective for loading and releasing BPs at doses that can inhibit excessive bone resorption without affecting osteoblasts. In vivo studies in relevant animal models are necessary to explore the effect of our injectable BP-combined biomaterial on femur bone structure by performing three-dimensional microtomography analysis, histological studies and SEM observations. Firstly, in rat model, our BP-combined CaP matrix significantly improved the bone micro-architecture as compared to CaP alone. The implantation of the BP-loaded biomaterial within proximal femurs of osteoporotic ewes led to a significant increase in relative bone content and an improvement of its micro-architecture. These modifications were confirmed by histological and SEM observations, which revealed CaP granule resorption and new bone trabeculae formation. This approach could be considered in the future for preventing osteoporotic fractures that are preferentially localized in the proximal femur, vertebral bodies or wrist. © 2010 Elsevier Ltd.


Patent
Graftys Inc., University of Nantes and French National Center for Scientific Research | Date: 2010-03-03

The present invention relates to a galliated calcium-phosphate biomaterial comprising a gallium-doped phosphocalcic compound of formula (I): Ca(_(005-1 5X))Ga_(x)(POO_(4))7, wherein 0


Patent
Graftys Inc., University of Nantes and French National Center for Scientific Research | Date: 2014-11-14

The present invention relates to a macroporous, resorbable and injectable apatitic calcium-phosphate cement with a high compressive strength useful as bone cement and releasing a bone resorption inhibitor, preparation method and uses thereof.


Patent
Graftys Inc. and French National Center for Scientific Research | Date: 2010-09-15

The present invention relates to a gallium-doped phosphocalcic compound of formula (I):Ca_((10.5-1.5x))Ga_(x)(PO_(4))_(7)(I)wherein 0 < x < 1 and the salts, hydrates and mixtures thereof. The invention further relates to a solid state process and a process in solution for the manufacture of such compounds and the use thereof for the preparation of a biomaterial, in particular a self-setting calcium-phosphate cement (CPC).


PubMed | University of Nice Sophia Antipolis, French National Center for Scientific Research, University of Nantes and Graftys Inc.
Type: | Journal: Journal of tissue engineering and regenerative medicine | Year: 2017

Calcium phosphate-based (CaP) 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 in the present work 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, accompanied by a successful bone ingrowth and bone marrow reconstruction, as evidenced by histological analysis. Moreover, quantitative micro-CT analysis of implants revealed that Ga enhanced total defect filling. Lastly, we took advantage for the first time of a particular mode of non-linear microscopy (second-harmonic generation) to quantify in vivo bone tissue reconstruction within a CaP bone substitute. By doing so, we showed that Ga exerted a positive impact on mature organized collagen synthesis. As a whole, our data support the hypothesis that Ga represents an attractive additive to CaP biomaterials for bone reconstructive surgery.


Patent
Graftys Inc. and French National Center for Scientific Research | Date: 2010-09-15

The present invention relates to a galliated calcium-phosphate biomaterial comprising a gallium-doped phosphocalcic compound of formula (I):Ca_((10.5-1.5x))Ga_(x)(PO_(4))_(7)(I)wherein 0 < x < 1 and the salts, hydrates and mixtures thereof and/or a calcium deficient apatite structure with in particular a (Ca + Ga)/P molar ratio in the range of 1.3 to 1.67, and a gallium content up to 4.5 % by weight. It also relates to processes of preparation of such materials and uses thereof, in particular as dental or bony implants. It further relates to a kit comprising a galliated calcium-phosphate biomaterial in combination with a fluid component. It finally relates to methods of use of the galliated calcium-phosphate biomaterial, notably for III) ions increase radio-opacity after bone implantation and can be released for inhibiting bone resorption.


Zhang J.,University of Nantes | Liu W.,University of Nantes | Schnitzler V.,University of Nantes | Schnitzler V.,Graftys Inc. | And 2 more authors.
Acta Biomaterialia | Year: 2014

Since their initial formulation in the 1980s, calcium phosphate cements (CPCs) have been increasingly used as bone substitutes. This article provides an overview on the chemistry, kinetics of setting and handling properties (setting time, cohesion and injectability) of CPCs for bone substitution, with a focus on their mechanical properties. Many processing parameters, such as particle size, composition of cement reactants and additives, can be adjusted to control the setting process of CPCs, concomitantly influencing their handling and mechanical performance. Moreover, this review shows that, although the mechanical strength of CPCs is generally low, it is not a critical issue for their application for bone repair - an observation not often realized by researchers and clinicians. CPCs with compressive strengths comparable to those of cortical bones can be produced through densification and/or homogenization of the cement matrix. The real limitation for CPCs appears to be their low fracture toughness and poor mechanical reliability (Weibull modulus), which have so far been only rarely studied. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Patent
Graftys Inc., Ecole Nationale Veterinaire De Nantes and University of Nantes | Date: 2013-09-03

The present invention concerns a composition useful as bone substitute comprising one or more calcium-phosphate compounds in association with an analgesic. It also refers to a preparation process of said composition, a preparation process of a drug-combined device comprising said composition, the drug combined device thus obtained, a kit comprising said composition and the use of said composition for the preparation of a drug-combined device useful for filling a bony defect caused in the iliac crest by collection of auto-graft bone, as a scaffold for tissue engineering and to produce a dental or bony implant.


Patent
University of Nantes and Graftys Inc. | Date: 2010-03-03

The present invention relates to a gallium-doped phosphocalcic compound of formula (I): Ca_((10.5-1.5x))Ga_(x)(PO_(4))_(7), wherein 0


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