Preparation And Biodegradation Of Spherical Calcium Carbonate/Hydroxyapatite Composites

As the most crucial inorganic constituent of bone and teeth, hydroxyapatite（HAP） is often used as a scaffold in bone engineering due to its excellent biocompatibility, osteo-conductivity and adsorptivity. However, HAP degrades slowly and can not provide the space for the new bone. Therefore, it is very important to improve the biodegradation in injectable bone tissue engineering.In this study, spherical CaCO₃ are fabricated in the presence of the silk sericin and then transformed into porous hydroxyapatite（HAP） microspheres via hydrothermal method. The degradation behavior of obtained CaCO₃, HAP and their mixture was investigated in vitro. The obtained CaCO₃ and HAP microspheres are injected into subcutaneous tissue of ICR mice with the assistance of sodium alginate. The result in vivo showed their enhance degradation and cytocompatibility with a mild inflammation response. The drug loading and release of CaCO₃ and HAP was investigated. And HAP showed an effective drug loading and controllable drug release. The results are as following:1. Spherical CaCO₃ were fabricated in the presence of the silk sericin and they were used as template to transform into porous HAP microspheres via hydrothermal method. The biocompatibility was investigated through the MG-63 human osteosarcoma cells culture on the CaCO₃ and HAP microspheres in vitro. The results showed that the cells can attached and spread actively on the samples. T2. Different percent CaCO₃ and HAP were kept in 50 mM Tris-HCl solution at pH 7.40 and at 37 °C maintaining the liquid-to-solid ratio of 0.4 mL/mg with a shaking speed at 110 rpm. the total weight loss of HAP microspheres are almost 24.3% after immersing in pH 7.40 Tris-HCl buffer solution for 12 weeks, which is far slower than that of spherical CaCO₃（97.5%）. The degradation speed of their mixtures could be adjusted through changing the proportion of CaCO₃ and HAP. The addition of sodium alginate（SA） into CaCO₃ or HAP to form an injectable biomaterial showed an elevated degradation pattern and cytocompatibility with a mild inflammation response in ICR mice groin muscle. The HE staining revealed that the implantation bed of CaCO₃ shows faster tissue fiber penetration, degradation and vessel ingrowth. This indicates that CaCO₃ could be used as an auxiliary composition to improve the degradation rate of biomedical composite. The results reveal that the appropriate ratio of CaCO₃ and HAP may be a promising biomaterial for bone repair.3. CaCO₃ and HAP microspheres were used as a carrier of DOX·HCl. The results showed CaCO₃ had the initial burst release and HAP had a better drug loading and sustained-release properties. The drug loading CaCO₃ and HAP can kill the Huh-7 cells in 7 days in vitro.