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Vigneux-de-Bretagne, France

Plank C.,TU Munich | Eglin D.,AO Research Institute Davos | Fahy N.,National University of Ireland | Sapet C.,OZ Biosciences | And 6 more authors.
European Journal of Nanomedicine | Year: 2012

The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand. A gene activated matrix is a biomaterial with embedded gene vectors that will genetically modify cells embedded in or colonising the matrix. The platform comprises modules that self-adapt to the biological environment and that can be independently addressed with endogenous biological and exogenous physical or pharmacological stimuli, resulting in a temporally and spatially coordinated growth factor gene expression pattern. This reproduces, within the matrix, key elements of natural tissue formation. The modules are a biomimetic hyaluronan gel, a ceramic matrix, growth factor-encoding gene vector nanoparticles, magnetic nanoparticles and mesenchymal stem cells. Anatomical adaptivity is achieved with engineered thermal properties of the polymer matrix, which embeds other modules, selected according to functional requirements. Mechanical support is provided by Micro Macroporous Biphasic Calcium Phosphate (MBCP ™ ), a resorbable material approved for clinical use. Spatiotemporal control of bioactivity and responsiveness to physiological conditions is represented, firstly, in the spatial distribution and release profiles of gene vectors within the composite matrix and, secondly, by letting local and external biological or physical stimuli activate the promoters driving the expression of vector-encoded growth factor transgenes. This concept is implemented by a multidisciplinary team from leading European institutions. Here, we report on the concepts, objectives and some preliminary results of the GAMBA project which is funded in 7th Framework Programme of the European Union THEME [NMP-2009-2.3-1], Biomimetic gels and polymers for tissue repair. © 2012 by Walter de Gruyter • Berlin • Boston.


Daculsi G.,University of Nantes | Briand S.,Nantes Hospital | Goyenvalle E.,ONIRIS LBBTOC | Aguado E.,ONIRIS LBBTOC | Baroth S.,Biomatlante SA
Key Engineering Materials | Year: 2012

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. © (2012) Trans Tech Publications.


Miramond T.,University of Nantes | Miramond T.,Biomatlante SA | Rouillon T.,University of Nantes | Daculsi G.,University of Nantes
Key Engineering Materials | Year: 2015

Solid-state transformation of CDA at high temperature has been investigated using TEM microscopy and diffraction from sintered biphasic calcium phosphate (hydroxyapatite-HA, and beta-tricalcium phosphate-TCP). Microcrystals, between 200nm and 800nm approximately, separated by grain boundaries were found to be either HA-HA or TCP-TCP, but not HA-TCP, suggesting that heteroepitaxial growth is very unlikely between these two orthophosphates. TEM-correlated EDX elemental analysis also demonstrated a higher ionic substitution (Na, Mg) of TCP phase. © (2015) Trans Tech Publications, Switzerland.


Changseong K.,Yonsei University | Cho K.S.,Yonsei University | Daculsi C.,Biomatlante SA | Seris G.E.,Bordeaux University Hospital Center | And 2 more authors.
Key Engineering Materials | Year: 2014

Restoring alveolar bone following tooth extraction or pathological diseases is important, and recent efforts have been made to overcome the use of autografts during dental implantation. Although micro-macroporous biphasic calcium phosphate (MBCP™) has performed well in orthopedic procedures, few studies have investigated its use in dentistry. Here, we report a greater than eight-year clinical follow-up of bone regeneration using MBCP™ after sinus grafting. MBCP™ technology is a unique mixture of hydroxyapatite and β-tricalcium phosphate, which displays both macroporosity and microporosity. A total of 25 patients (33 implantation sites) were evaluated by X-rays, and their pre-operative and immediate post-operative bone heights were measured. After approximately six months, dental implantation was performed. Subsequently, X rays were performed each year, and bone height was measured. In all cases, radio-opacity of the implantation area decreased with time, indicating resorption and bone in growth at the expense of the MBCP™ material. After one year, the implantation area had the appearance of physiological bone and <11% of height loss was observed. Strikingly, the newly formed bone was preserved after 7-8 years of follow-up, with only <14% of height loss recorded. We demonstrate that sinus grafting followed by dental implantation with a resorbable and bioactive synthetic bone graft material (MBCP™ technology) safely and efficiently supports dental implantation. © (2014) Trans Tech Publications, Switzerland.


Daculsi G.,University of Nantes | Baroth S.,University of Nantes | Baroth S.,Biomatlante SA | LeGeros R.,New York University
Ceramic Engineering and Science Proceedings | Year: 2010

We developed 20 years ago, biphasic calcium phosphate ceramics (BCP). The BCP concept is determined by a balance of the more stable HA phase and more soluble TCP. BCP is gradually resorbed, seeding new bone formation. The main attractive feature of BCP is the ability to form a direct bone bonding resulting in a strong interface. This interface is the result of a sequence of events involving interaction with cells; and dissolution/precipitation processes. The efficiency of BCP concept was due to: (1) partial dissolution of the CaP ceramic macrocrystals inducing an increase in the calcium and phosphate ions concentration in the local microenvironment; (2) formation of carbonate hydroxyapatite CHA, (3) incorporation of these microcrystals with the collageneous matrix and non collagenic proteins like growth factors and others, in the newly formed bone. The BCP/bone interface represent a dynamic process, including physico-chemical processes, crystal/proteins interactions, cells and tissue colonization, bone remodelling. BCP have the advantage of bioactivity control by changing the HA and β-TCP ratio. BCP are osteoconductive and osteoinductive through appropriate critical geometry of microporosity. Besides the medical and dental applications, BCP has a potential for other applications such as delivery system for drugs, antibiotics, hormones; carriers for growth factors; scaffolds for tissue engineering. Specific matrices for combination with bone marrow or stem cells; and the need of material for Minimal Invasive Surgery (MIS) induced the development of injectable BCP granules. This paper summarizes 20 years of development of BCP and derivatives.

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