A dual constant‐composition titration system as an <i>in vitro</i> resorption model for comparing dissolution rates of calcium phosphate biomaterials

Abstract

It has been postulated that the in vivo resorption rates of calcium-phosphate bone-graft materials are closely related to their dissolution rates in demineralizing solutions having ionic compositions mimicking the acidic environment produced by osteoclasts. Thus, it should be possible to use an in vitro model to produce dissolution-rate data of calcium-phosphate materials as a starting point for predicting in vivo resorption properties. Direct pH measurements of the extracellular fluid from bone-resorbing cells showed that the pH was as low as 3. In the present study, a dual constant-composition dissolution system was used as an in vitro resorption model to compare dissolution rates of different calcium-phosphate materials. NIST standard reference hydroxyapatite (HA), dicalcium-phosphate dihydrate (DCPD), and calcium-phosphate cement (CPC) discs of known dimensions (6-mm d x 3-mm h) were allowed to dissolve at 37 degrees C in a solution that had an inorganic composition similar to that of serum ([Ca] = 1.15 mmol/l; [P] = 1.2 mmol/l; [KCl] = 133 mmol/l) and a pH of 3.0. A Ca ion-specific electrode and a pH electrode were used to control the addition of titrants to compensate for the increases in calcium and phosphate concentrations, respectively, in the demineralizing solution. The rate and stoichiometry (Ca/P molar ratio) of dissolution were obtained from the titration data. Each solid dissolved at an approximately constant rate during the dissolution process. The dissolution rates, expressed in mg cm(-2) min(-1), (mean +/- standard deviation, n = 5) were for HA: 6.58 +/- 1.22; DCPD: 21.0 +/- 2.6; and CPC: 8.21 +/- 0.73. DCPD dissolved three times faster than HA (p < 0.05). CPC dissolved 1.2 times faster than HA but the difference was not statistically significant (p > 0.05). This model can be used to study the rate and stoichiometry of dissolution of calcium-phosphate bone-graft materials and coatings under a wide range of mineral saturation conditions.