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.

The main goal of this study was to succeed in the relevant association of well-known osteoconductive biphasic calcium phosphate (BCP) made of Hydroxyapatite (20% HA) and β-Tricalcium Phosphate (80% β-TCP) crystallographic phases and resorbable poly (L-lactide-co-D,L-lactide)(PLDLLA) 3D matrices synthesized by electrospinning. Two types of mineral particles were obtained, BCP new hollow granules, and classical BCP particles. It appeared that hollow shells/PLDLLA composite 3D matrices allowed higher cell adhesion in vitro, thanks to internal concavities and are promising scaffolds in terms of cell carrying.

Les greffes osseuses autologues et l’os de banque de tissus sont largement utilisés en clinique pour des reconstructions osseuses. Cependant, ces greffons présentent des inconvénients tels qu’un deuxième site chirurgical, une quantité limitée ou de rejets. L’ingénierie tissulaire osseuse consiste à associer des cellules souches mésenchymateuses (CSM) du patient à des biomatériaux pour régénérer le tissu osseux. Des CSM issues de la moelle osseuse ont été cultivées sur des céramiques de phosphate de calcium biphasé (BCP) et implantées en site sous-cutané chez la souris immunodéficiente. Les CSM prolifèrent sur les biomatériaux, se différentient en ostéoblastes et produisent une matrice extracellulaire en collagène in vitro. Les construits 3D hybrides induisent la formation d’un néo tissu osseux minéralisé au contact de la céramique. Les hydrogels associés à des particules de BCP sont également évalués pour injecter les cellules dans des défauts osseux. Cependant, la culture des CSM en hydrogels nécessite des sites d’adhésion cellulaire et une migration des cellules. L’association de moelle osseuse concentrée autologue (MOCA) ou de CSM avec des céramiques BCP pendant l’intervention chirurgicale est envisageable mais se heurte à des obstacles réglementaires pour aboutir à des applications cliniques.

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.

Calcium phosphate bioceramic granules associated with hydrosoluble polymers were developed as bone substitutes for various maxillofacial and orthopaedic applications. These resorbable bone substitute putties, support and regenerate bone tissue after implantation. The efficiency of these multiphasic materials is due to the osteogenic and osteoconductive properties of the microporous biphasic calcium phosphate bioceramic. The associated hydrosoluble polymers are considered as carriers in order to achieve the rheological properties of putty mouldable bone substitutes. In this study, 2 types of hydrosoluble polymers were tested. The first one is a thermo reversible polymer (polaxamer) and the second one is a reticulated hydrogel (polysaccharidic) obtain by e-beam irradiation. The 2 types of hydrogels were associated to microporous biphasic calcium phosphate (HA/TCP) bioceramics and implanted in goat vertebrae bodies. No foreign body reactions were observed in the two samples. This study demonstrates good handling of the two putties, good biocompatibility, high resorbability and bone ingrowth at the expense of the materials.

Although autologous or allogenous bone grafting materials are widely used to repair skeletal tissue, their limitations induce surgeons to look for more advanced therapies such as tissue engineering. However, bone tissue engineering still lacks proofs of clinical efficacy, possibly due to the inadequate design of the tissue-engineered constructs in relation to the natural tissue. Our aim is therefore to design an engineered construct that mimics the three main components of bone (osteoblastic cells, collagen extracellular matrix and apatite crystals). Human bone marrow contains mesenchymal stem cells that differentiate into osteoblasts. These osteoprogenitors have been cultured on calcium phosphate ceramics producing collagen extracellular matrix in vitro and inducing ectopic bone tissue formation in vivo. Cellulosic hydrogels associated to calcium phosphate particles have been used for preparing injectable bone substitutes. These injectable materials are particularly attractive for delivering osteoprogenitor cells in to bone defects using minimal invasive surgery. Bone tissue engineering using autologous MSC and biomaterials may become in future an attractive approach for the reconstruction of large bone defects in orthopaedic, spine and maxillo-facial surgeries. (C) 2011 Elsevier Masson SAS. All rights reserved.

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.

We have developed a new injectable bone substitute combining specific granules of BCP with or without radiopaque elements with a reversible thermo sensitive resorbable carrier such as Pluronic F-127. The composite is liquid at ambient temperature and set as hydrogel at 37°C. Rabbit experiment demonstrates high biocompatibility and bone ingrowth at the expense of the injectable bioceramic composite.

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.

The purpose of this study ass to investigate the addition of round 80-200m granules shape radiopaque agents (RA) to synthetic Injectable Bone Substitute to improve contrast performance for minimal invasive surgery MIS. Composites were obtained by mixing BaSO4, Bi2O3, Lu2O3 or GdPO4 with calcium deficient apatite CDA which decompose during sintering process in BCP (60% HA, 40% β-TCP). Each composite was characterized: by XRD, FTIR. Biocompatibility was tested in vitro and in vivo in bony site (3 weeks implantation in rats). Primary results show that the suitable radiopaque BCP/RA composite (radiopacity intensity, biological responses) appeared to be BCP/Ba. Next works will complete the current studies on biological performance in association with different kind of resorbable injectable bone substitute as suspension, gel or calcium phosphate cements.

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.

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.