Synthesis of calcium carbonate microspheres via inert gas bubbling for orthopedic applications

Calcium carbonate (CaCO3) microspheres consisting of vaterite polymorph have been widely used in biomedical applications. Specifically, vaterite microspheres having hollow cores showed significant potential in drug delivery, however the spontaneous transformation of vaterite to other polymorphs in aqueous environments reduced its controlled in vivo release capability. In this work, calcite and aragonite microspheres having hollow/porous inner cores were synthesized -for the first time-using sodium dodecyl sulfate (SDS) stabilized nitrogen (N-2) bubbles as CaCO3 template in ethylene glycol (EG) solution and water as the precipitation medium. Results demonstrated that porous aragonite microspheres could be synthesized via N-2 gas incorporation, yet for the synthesis of hollow calcite microspheres, N-2 bubbles had be stabilized with SDS to be utilized as CaCO3 templates. The synthesized aragonite and calcite microspheres were found to be stable up to 5 days in Dulbecco's Modified Eagle's Medium (DMEM), and thus would not allow polymorphic transformation in aqueous environments, while promoting proliferation of human bone cells (hFOB) up to 5 days of culture. These findings -for the first time-identified a viable synthesis route for hollow/porous calcite and aragonite microspheres and indicated their promising use in orthopedic applications.