J. A. Planell

Calcium phosphate bone cements for clinical applications. Part I: solution chemistry.

Calcium phosphate cements have been the subject of many studies in the last decade because of their biocompatibility, their capacity to fill bone cavities and their hardening properties; properties which are desirable in a broad range of surgical applications. The setting and hardening of these materials are controlled by dissolution–precipitation chemical reactions at room or body temperature and involve crystalline phase transformations.

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.

Effective formulations for the preparation of calcium phosphate bone cements

In the system CaO−P2O5−H2O 13 different solids with varying Ca/P ratios are known. In addition calcium phosphates containing other biocompatible constituents like Na, or K, or Mg or Cl or carbonate, are known. Therefore, a large number of combinations of such compounds is possible which might result in the formation of calcium phosphate cements upon mixing with water. However, the number of calcium phosphates possibly formed by precipitation at room or body temperatures is limited to 12, which should limit the number of suitable combinations. In this study more than 450 different combinations of reactants have been investigated. The results were evaluated on the basis of the following criteria: (a) was the intended reaction product formed? (b) was the final setting time shorter than 60 min? (c) was the compressive strength after soaking for 1 day in Ringers solution at 37°C higher than 2 MPa? We found that 15 formulations satisfied all of these criteria. The distribution of cements synthesized in this way was 3 DCPD type, 3 CMP type, 6 OCP type and 3 CDHA type cements. The DCPD type cements were acidic during setting and remained that for a long time afterwards. CDHA type cements were neutral or basic during setting, and remained neutral after completion of the reaction. The OCP type cements were neutral both during and after setting. Two CMP type cements were basic both during and after setting. In this study compressive strengths were found up to 90 MPa. Also, in the literature values up to 90 MPa have been reported for this type of cement. Taking into account the excellent biocompatibility and the good osteoconductivity of calcium phosphates and the fact that these calcium phosphate cements can be injected into the site of operation, it may be expected that these materials will become the materials of choice for bone replacement and augmentation. Their suitability for the fixation of metal endoprostheses for joint replacement should be investigated as well.

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.

Osteotransductive bone cements

Abstract 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 ≍ 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 CDHA-type, CA-type and HA-type CPBCs as they have a higher compressive strength than human trabecular bone (10 MPa).

Calcium phosphate bone cements for clinical applications. Part II: Precipitate formation during setting reactions

Calcium phosphate bone cements (CPBC) have been of great interest in medicine and dentistry due to their excellent biocompatibility and bone-repair properties. In this article, a review is presented of the scientific literature concerning precipitate formation during setting reactions of CPBCs. Firstly, the available information has been classified according to the intended final product or calcium phosphate formed during setting reactions. Taking the final product into account, a second classification has been made according to the calcium phosphates present in the original powder mixture. This is the most natural classification procedure because it is based on thermodynamic reasons supported by solubility diagrams for the calcium phosphate salts. By understanding the thermodynamics of calcium phosphate salts in an aqueous solution at room or body temperature it is possible to optimize the manufacturing technology involved in the production of CPBCs. Knowledge of the limitations of this thermodynamic approach opens up new possibilities in the search for CPBCs with better in vitro and in vivo properties for clinical applications.

Mechanical and rheological improvement of a calcium phosphate cement by the addition of a polymeric drug

A polymeric acrylic system supporting a derivative of the aminosalicylic acid was incorporated in a calcium phosphate cement, with the aim not only to achieve some pharmacological effects but to obtain an improvement of its mechanical and rheological properties. It is known that, besides the analgesic and anti-inflammatory properties, the salicylic group presents a calcium complexation ability. The inorganic phase of the cement consisted of alpha-tricalcium phosphate [alpha-Ca(3)(PO(4))(2)] and precipitated hydroxyapatite added as a seed. The liquid phase was an aqueous solution of Na(2)HPO(4). The polymeric drug increased the injectability of the cement. The hydrolysis of the alpha-tricalcium phosphate into calcium-deficient hydroxyapatite proceeded at a lower rate because of the addition of the polymeric drug. As a consequence, the cement hardening was slightly slower, although the final compressive strength was 25% higher. The bending strength increased from 5 to 9 MPa with the addition of the polymeric drug. The strengthening of the structure was related to the reduction of porosity and the lower size of the precipitated crystals, as observed by scanning electron microscopy.

New aspects of the effect of size and size distribution on the setting parameters and mechanical properties of acrylic bone cements

The effect of the size and the size distribution of poly(methyl methacrylate) (PMMA) beads on the classical kinetic parameters, peak temperature and setting time, for acrylic bone cement formulations prepared with PMMA particles in the range 10-60 microns of average diameter and a relatively wide size distribution is analysed. In addition, the combined effects of the concentration of the free radical initiator benzoyl peroxide and the activator N, N-dimethyl-4-toluidine for the different particle sizes are studied and compared with those commercially available formulations like CMW or Rostal. The results obtained indicated that the use of PMMA particles with average diameter of 50-60 microns, and a relatively wide size distribution (10-140 microns diameter), significantly changes the curing parameters (peak temperature and setting time) of the cement formulations in comparison with the classical behaviour of the commercial systems of CMW and Rostal, without any noticeable loss in the mechanical properties, such as tensile strength, elastic moduli, and compressive strength and plastic strain.

Formation of α-Widmanstätten structure: effects of grain size and cooling rate on the Widmanstätten morphologies and on the mechanical properties in Ti6Al4V alloy

Abstract The coarseness of the transformed β-heat treated Ti6Al4V has a strong influence on its properties. The effects of solution temperatures and cooling rate on the Widmanstatten morphologies and on mechanical properties have been determined. The α-Widmanstatten plates size increases when the cooling rate decreases and a certain decrease of α-allotromorphous phase size at the grain boundaries can be observed when the cooling rate is increased. The tensile strength can be reduced about 80 MPa with the slower cooling rate from the β annealing temperatures when comparing air cooling to water quenching for thinner section sizes.

PRODUCTION AND CHARACTERIZATION OF NEW CALCIUM PHOSPHATE BONE CEMENTS IN THE CAHPO4-ALPHA -CA3(PO4)2 SYSTEM : PH, WORKABILITY AND SETTING TIMES

The initial setting properties of calcium phosphate cements in the CaHPOv4–α-Ca3(PO4)2 (DCP–α-TCP) system have been investigated. Interest was focused on the pH, workability, cohesion time and initial and final setting times. The addition of CaCO3 modified the structure of the cement reaction product such that it became more similar to the apatite phase in bone mineral. The addition of 10% w/w of CaCO3 reduced the viscosity of the cement pastes resulting in an increase in initial and final setting times and improved injectability.