No abstract

The aim of this study was to compare the bone colonization of a macroporous biphasic calcium phosphate (MBCP) ceramic in different sites (femur, tibia, and calvaria) in two animal species (rats and rabbits). A critical size defect model was used in all cases with implantation for 21 days. Bone colonization in the empty and MBCP-filled defects was measured with the use of backscattered electron microscopy (BSEM). In the empty cavities, bone healing remained on the edges, and did not bridge the critical size defects. Bone growth was observed in all the implantation sites in rats (approx. 13.6 -36.6% of the total defect area, with ceramic ranging from 46.1 to 51.9%). The bone colonization appeared statistically higher in the femur of rabbits (48.5%) than in the tibia (12.6%) and calvaria (22.9%) sites. This slightly higher degree of bone healing was related to differences in the bone architecture of the implantation sites. Concerning the comparison between animal species, bone colonization appeared greater in rabbits than in rats for the femoral site (48.5% vs. 29.6%). For the other two sites (the tibia and calvaria), there was no statistically significant difference. The increased bone ingrowth observed in rabbit femurs might be due to the large bone surface area in contact with the MBCP ceramics. The femoral epiphysis of rabbits is therefore a favorable model for testing the bone-bonding capacity of materials, but a comparison with other implantation sites is subject to bias. This study shows that well-conducted and fully validated models with the use of small animals are essential in the development of new bone substitutes.

In this animal model, a biomimetic calcium phosphate coating gave similar osseointegration to the SLA surface. This biomimetic coating method may enhance the apposition of bone onto titanium dental implants.

Two porous titanium implants with a pore size diameter of 800 and 1200 microm (Ti800 and Ti1200) and an interconnected network were manufactured using rapid prototyping. Their dimensions and structure matched those of the computer assisted design. The porosity of the implants was around 60%. Their compressive strength and Young's modulus were around 80 MPa and 2.7 GPa, respectively. These values are comparable to those of cortical bone. The implants were implanted bilaterally in the femoral epiphysis of 15 New Zealand White rabbits. After 3 and 8 weeks, abundant bone formation was found inside the rapid prototyped porous titanium implants. For the Ti1200 implants, bone ingrowth was (23.9 +/- 3.5)% and (10.3 +/- 2.8)%, respectively. A significant statistical difference (p < 0.05) was found for bone ingrowth in the Ti1200 between the two delays. The percentage of bone directly apposited on titanium was (35.8 +/- 5.4)% and (30.5 +/- 5.0)%. No significant difference was found for bone-implant contact between the different time periods and pore sizes. This work demonstrates that manufacturing macroporous titanium implants with controlled shape and porosity using a rapid prototyping method is possible and that this technique is a good candidate for orthopedic and maxillofacial applications.

An ageing population implies an increase in bone and dental diseases, which are in turn a source of numerous handicaps. These pathologies are an expensive burden for the European health system. As no specific bioactive materials are efficient enough to cope with this burden, we have to develop an injectable, mouldable, self-hardening bone substitute to support bone tissue reconstruction and augmentation. New, highly bioactive and suitable biomaterials have been developed to replace bone grafts in orthopedic revision and maxillofacial surgery for bone augmentation. These mouldable, self-hardening materials are based on the association of MBCP Biphasic Calcium Phosphate Granules and Tissucol Fibrin Sealant. The in vivo evaluation of ingrowth in relation to the composite was made in an experiment on rabbits. The results indicate that in the presence of fibrin sealant, newly-formed bone developed at a small distance from the surface of the calcium phosphate ceramic. Two different bone apposition processes were identified. Without the fibrin component (MBCP group), bone rested directly on the surface of the granules. This observation is commonly described as osteoconduction in calcium phosphate materials. On the contrary, the presence of the fibrinogen component seemed to modify this standard osteoconduction phenomenon: the newly-formed bone essentially grew at a distance from the surface of the granules, on the fibrillar network, and could be considered as an inductive phenomenon for osteogenic cell differentiation from mesenchymal stem cells.

Calcium phosphate (Ca-P) ceramics are currently used in various types of orthopaedic and maxillofacial applications because of their osteoconductive properties. Fibrin glue is also used in surgery due to its haemostatic, chemotactic and mitogenic properties and also as scaffolds for cell culture and transplantation. In order to adapt to surgical sites, bioceramics are shaped in blocks or granules and preferably in porous forms. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial. The aim of this work is to study the osteogenic properties of this composite material using two different animal models. The formation of newly formed bone (osteoinduction) and bone healing capacity (osteconduction) have been study in the paravertebral muscles of sheep and in critical sized defects in the femoral condyle of rabbits, respectively. The different implantations sites were filled with composite material associating Ca-P granules and fibrin glue. Ca-P granules of 1-2 mm were composed with 60% of hydroxyapatite and 40% of beta tricalcium phosphate in weight. The fibrin glue was composed of fibrinogen, thrombin and other biological factors. After both intramuscular or intraosseous implantations for 24 weeks and 3, 6, 12 and 24 weeks, samples were analyzed using histology and histomorphometry and mechanical test. In all cases, the newly formed bone was observed in close contact and around the ceramic granules. Depending on method of quantification, 6.7% (with BSEM) or 17% (with micro CT) of bone had formed in the sheep muscles and around 40% in the critical sized bone rabbit defect after 24 weeks. The Ca-P/fibrin material could be used for filling bone cavities in various clinical indications.

Calcium phosphate bioceramic granules associated with hydrosoluble polymers were developed as bone substitutes for various maxillofacial and orthopaedic applications. These injectable bone substitutes, support and regenerate bone tissue and resorb after implantation. The efficiency of these multiphasic materials is due to the osteogenic and osteoconductive properties of the microporous biphasic calcium phosphate. The associated hydrosoluble polymers are considered as carriers in order to achieve the rheological properties of injectable bone substitutes (IBS). In this study, we used 2 semi synthetic hydrosoluble polymers of polysaccharidic origin. The hydroxy propyl methyl cellulose (HPMC), with and without silane, was combined with microporous BCP granules. The presence of silane induced considerable gelation of the suspension. The 2 IBS used (without gelation, IBS1, with gelation, IBS2) were implanted in critical size femoral epiphysis defects in rabbits. No foreign body reactions were observed in either sample. However, because of the higher density from gelation, cell colonisation followed by bone tissue ingrowth was delayed over time with IBS2 compared to the IBS1 without gelation. The results showed resorption of the BCP granule and bone ingrowth at the expense of both IBS with different kinetics. This study demonstrates that the hydrogel cannot be considered merely as a carrier. The gelation process delayed cell and tissue colonisation by slow degradation of the HPMC Si, compared to the faster release of HPMC with IBS1, in turn inducing faster permeability and spaces for tissue ingrowth between the BCP granules.

This study demonstrated that the choice of a natural (aprotinin) or synthetic (tranexamic acid) antifibrinolytic agent in the fibrin sealant associated with calcium phosphate granules and used as a bone substitute had no effect on the bioactivity of the composite. It remained efficient in bone reconstruction, no adverse effects were observed, and the bony ingrowth was qualitatively and quantitatively equivalent with the two types of fibrin sealant.