Drug and ion releasing tetracalcium phosphate based dual action cement for regenerative treatment of infected bone defects

Calcium phosphate cements (CPCs) are ideally suited for the local delivery of antibiotics in infected bone defects as they have multiple binding sites for loading various drugs. CPCs can also be substituted with ions such as Ag+, Zn2+, Mg2+, Sr2+, etc., to exhibit extended broad-spectrum antimicrobial activity. Strontium (Sr) in particular is known to enhance the new bone formation and decrease bone resorption. The current work aims to develop a dual action tetracalcium phosphate (TTCP) based cement which releases both the Sr2+ ion and ornidazole antibiotic drug for the treatment of bone infections. The TTCP with Sr2+ ion substitution was prepared by the solid state reaction method and it was used to form ornidazole loaded CPC. The ornidazole loaded cement prepared using 8 at% Sr substituted TTCP (8SCPC-O) showed complete hydroxyapatite (HA) formation in phosphate buffered solution at the end of 1 week. Fine needle-shaped HA crystals were observed in 8SCPC-O cement. In vitro drug release studies showed an accelerated ornidazole release from the 8SCPC-O sample when compared to samples without Sr substitution. Ornidazole releasing cements were found to be biocompatible with skeletal myoblast (L6) cells. Antibacterial activity of ornidazole releasing cement was evident from day 1 onwards against E. coli. The above results suggest 8SCPC-O as a good candidate for treating local bone infections.