Intelligent Drug Delivery System for Artificial Bone Cement Based on Hydroxyapatite-Related Organic/Inorganic Composite Materials

Abstract

The self-setting apatite-based bone cement, prepared using the solubility phase diagram of calcium phosphates, consists of metastable calcium phosphates and can be transformed to the low-crystallinity apatite with bio-affinity to natural bones. Various drugs were kneaded into the cement to create an artificial bone cement with sustained drug release capability and the drug release from the cement matrices can be controlled based on the parameters of the Higuchi equation, such as drug concentration, porosity, granular diameter, and diffusion coefficient. Results from in vitro and in vivo drug release experiments suggested that in vivo drug release from the apatite cement was dependent on calcium concentration in the body fluids. The results indicated that anti-osteoporosis drug release from apatite bone cement could be controlled based on the severity of the disease in osteoporotic rats. In addition, the amount of diseased bone in the rat increased with the apatite bone cement. Furthermore, anti-osteoporotic drugs were added to the apatite-collagen composite cement for the manufacture of three-dimensional perforated macro-porous bone cell scaffold. The collagen-HAp cement containing DNA complex was administered, and the growth of cancer cells was effectively suppressed by the continuous DNA release of the injected collagen-HAp cement containing DNA complex. This highly functional artificial bone was shown to be suitable for bone regeneration.