Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement.

Clinical requirements for calcium phosphate bone cements were formulated in terms of the initial setting time, the final setting time, the cohesion time and the ultimate compressive strength. Three cement formulations were tested. The previously developed Biocement H was made of a powder containing alpha-tertiary calcium phosphate and precipitated hydroxyapatite. Biocement B2 powder was made by adding some CaCO3 to Biocement H, whereas Biocement B1 was made by adding some CaCO3 but with simultaneous adjustment of the amount of precipitated hydroxyapatite.The liquid/ powder ratio of the cement paste and the accelerator concentrations (percentage Na2HPO4) in cement liquid were varied. For Biocement H there was no combination of L/P ratio and percentage Na2HPO4 for which all clinical requirements were satisfied. However, there was an area of full compliance for Biocements B1 and B2, of which that for B1 was the largest. Therefore, Biocement B1 may be applied in clinical situations as those in orthopaedics, plastic and reconstructive surgery and oral and maxillofacial surgery, even when early contact with blood is inevitable.

Addition of cohesion promotors to calcium phosphate cements.

Many calcium phosphate cements (CPC) pastes tend to disintegrate upon early contact with blood or other aqueous (body) fluids, which inhibits the use of these materials for clinical use as for bone repair, reconstruction and augmentation. In studies on CPCs based on tetracalcium phosphate and dicalcium hydrogen phosphate others have suggested to use sodium alginate, cellulose derivatives or chitosan derivatives dissolved in the cement liquid for improving the cohesion of CPC pastes. In this study 10 other organic compounds were shown to act as cohesion promotors in the case of CPCs based on alpha-tertiary calcium phosphate as the main active ingredient.

Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials.

This study used synchrotron X-ray microtomography on a micron scale to compare three-dimensional (3D) bone ingrowth after implantation of various calcium phosphate bone substitutes in a rabbit model. The advantage of using this new method for the study of biomaterials was then compared with histomorphometry for analysis of interconnection and bone ingrowth. The study focused on the newly formed bone-biomaterial interface. Macroporous Biphasic Calcium Phosphate (MBCP) ceramic blocks and two different injectable calcium phosphate biomaterials [an injectable bone substitute (IBS) consisting of a biphasic calcium phosphate granule suspension in hydrosoluble polymer and a calcium phosphate cement material (CPC)] were studied after in vivo implantation. Absorption or phase-contrast microtomography was performed with the dedicated set-up at beamline ID22. Experimental spatial resolution was between 1 and 1.4 microm, depending on experimental radiation. All calcium phosphates tested showed osteoconduction. IBS observations after 3D reconstruction showed interconnected bioactive biomaterial with total open macroporosity and complete bone ingrowth as early as 3 weeks after implantation. This experimentation was consistent with two-dimensional histomorphometric analysis, which confirmed its suitability for biomaterials. This 3D study relates the different types of bone substitution to biomaterial architecture. As porosity and interconnection increase, bone ingrowth becomes greater at the expense of the bone substitute: IBS>MBCP>CPC.

Noninvasive bone replacement with a new injectable calcium phosphate biomaterial.

The use of injectable calcium phosphate (CaP) biomaterials in noninvasive surgery should provide efficient bone colonization and implantation. Two different kinds of injectable biomaterials are presently under development: ionic hydraulic bone cements that harden in vivo after injection, and an association of biphasic calcium phosphate (BCP) ceramic granules and a water-soluble polymer vehicle (a technique particularly investigated by our group), providing an injectable CaP bone substitute (IBS). In our study, we compared these two approaches, using physicochemical characterizations and in vivo evaluations in light microscopy, scanning electron microscopy, and three-dimensional microtomography with synchrotron technology. Three weeks after implantation in rabbit bone, both biomaterials showed perfect biocompatibility and bioactivity, but new bone formation and degradation of the biomaterial were significantly greater for BCP granules than for ionic cement. Newly formed bone developed, binding the BCP granules together, whereas new bone grew only on the surface of the cement, which remained dense, with no obvious degradation 3 weeks after implantation. This study confirms that BCP granules carried by a cellulosic polymer conserve bioactivity and are conducive to earlier and more extensive bone substitution than a carbonated-hydroxyapatite bone cement. The presence of intergranular spaces in the BCP preparation, as shown on microtomography imaging, seems particularly favorable, allowing body fluids to reach each BCP granule immediately after implantation. Thus, the IBS functions as a completely interconnected ceramic with total open macroporosity. This new bone replacement approach should facilitate microinvasive bone surgery and local delivery of bone therapy agents.

Osteotransductive bone cements.

Calcium phosphate bone cements (CPBCs) are osteotransductive, i.e. after implantation in bone they are transformed into new bone tissue. Furthermore, due to the fact that they are mouldable, their osteointegration is immediate. Their chemistry has been established previously. Some CPBCs contain amorphous calcium phosphate (ACP) and set by a sol-gel transition. The others are crystalline and can give as the reaction product dicalcium phosphate dihydrate (DCPD), calcium-deficient hydroxyapatite (CDHA), carbonated apatite (CA) or hydroxyapatite (HA). Mixed-type gypsum-DCPD cements are also described. In vivo rates of osteotransduction vary as follows: gypsum-DCPD > DCPD > CDHA approximately CA > HA. The osteotransduction of CDHA-type cements may be increased by adding dicalcium phosphate anhydrous (DCP) and/or CaCO3 to the cement powder. CPBCs can be used for healing of bone defects, bone augmentation and bone reconstruction. Incorporation of drugs like antibiotics and bone morphogenetic protein is envisaged. Load-bearing applications are allowed for CHDA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).

Limited compliance of some apatitic calcium phosphate bone cements with clinical requirements.

Clinical requirements for calcium phosphate bone cements were formulated in terms of the initial setting time, the final setting time, the cohesion time and the ultimate compressive strength. Two cements were tested. Biocement H was made of a powder containing alpha-tertiary calcium phosphate and precipitated hydroxyapatite. Biocement F was made of a powder containing, in addition, some monetite. The liquid/powder (L/P) ratio was varied over the range 0.30-0.40 ml g(-1), whereas the accelerator concentration in the liquid was varied from 0%-4% Na2HPO4 in water. For Biocement H there was no combination L/P ratio and % Na2HPO4 for which all clinical requirements were satisfied. However, Biocement F had a certain area where this was the case. Therefore, it is expected that Biocement F can be applied in clinical situations such as orthopaedics, plastic and reconstructive surgery and oral and maxillofacial surgery, even when early contact with blood is inevitable.

Some factors controlling the injectability of calcium phosphate bone cements.

The injectability of four calcium phosphate bone cements (CPBCs) was measured using a commercial disposable syringe. It varied considerably with the cement powder composition, with the liquid/powder ratio, with the time after starting the mixing of liquid and powder, with the accelerator concentration (% Na2HPO4), and with the ageing time of the cement powder which was prepared by milling. The injectability test could be used to determine accurately the dough time of CPBCs. Relations between the setting time and the cohesion time are discussed.

Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement.

Clinical requirements for calcium phosphate bone cements were formulated in terms of the initial setting time, the final setting time, the cohesion time, and the ultimate compressive strength. Two cement formulations were tested. Biocement F was made of a powder containing alpha-tertiary calcium phosphate, precipitated hydroxyapatite, and monetite. Biocement D powder also contained CaCO3. The liquid/powder (L/P) ratio of the cement paste and the accelerator concentrations (% Na2HPO4) in the cement liquid were varied. For Biocement F there was a small area of combinations of L/P ratio and percent Na2HPO4 for which all clinical requirements were satisfied. This area covered only pastes that could be applied as doughs. However, Biocement D showed a much larger area of full compliance and it covered both doughlike and injectable pastes.

In vitro characterization and in vivo properties of a carbonated apatite bone cement.

This study evaluated the in vivo behavior of an injectable calcium phosphate bone cement implanted in bone defects at the distal end of rabbit femora. After 3 weeks, samples were harvested and processed for undecalcified sectioning. Scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared microspectroscopy showed direct contact of bone and cement without soft tissue interposition, biocompatibility, and bioactivity with osteoconductive properties.

Incorporation of a controlled-release glass into a calcium phosphate cement.

A so-called controlled-release glass was synthesized occurring in the system CaO-Na2O-P2O5. A certain sieve fraction of this glass was incorporated in a calcium phosphate cement, of which the powder contained alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate (DCP) and precipitated hydroxyapatite (HA). The glass appeared to retard the cement setting slightly and it reduced considerably the compressive strength after aging in aqueous solutions which were continuously refreshed. Scanning electron microscope (SEM) pictures and X-ray diffraction (XRD) patterns of the samples after 5 weeks of aging showed that the glass was not dissolved but that large brushite crystals were formed. Thereby, aging in CaCl2 solutions resulted in more brushite formation than aging in NaCl solutions. The brushite crystals did not reinforce the cement. Neither was the aged glass-containing cement weaker than it was before the brushite formation right after complete setting. In conclusion, the incorporation of controlled-release glasses into a calcium phosphate cement and subsequent aging in aqueous solutions did not result in the formation of macropores in the cement structure, but that of brushite crystals. This incorporation reduced the compressive strength of the cement considerably.