Abstract 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.

中文翻译：

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用于再生治疗感染性骨缺损的药物和离子释放磷酸四钙基双效骨水泥

摘要 磷酸钙骨水泥 (CPC) 非常适合在受感染的骨缺损中局部递送抗生素，因为它们具有多个结合位点来装载各种药物。CPCs 也可以被 Ag+、Zn2+、Mg2+、Sr2+ 等离子取代，以表现出广谱的抗菌活性。众所周知，锶 (Sr) 尤其能促进新骨形成并减少骨吸收。目前的工作旨在开发一种双作用磷酸四钙 (TTCP) 基骨水泥，该骨水泥可同时释放 Sr2+ 离子和奥硝唑抗生素药物，用于治疗骨感染。采用固相反应法制备了Sr2+离子取代的TTCP，并用于形成负载奥硝唑的CPC。使用 8 at% Sr 取代的 TTCP (8SCPC-O) 制备的奥硝唑负载水泥在 1 周结束时在磷酸盐缓冲溶液中显示出完全的羟基磷灰石 (HA) 形成。在 8SCPC-O 水泥中观察到细针状 HA 晶体。体外药物释放研究表明，与没有 Sr 取代的样品相比，8SCPC-O 样品中奥硝唑的释放加速。发现奥硝唑释放水泥与骨骼成肌细胞 (L6) 具有生物相容性。从第 1 天起，奥硝唑释放水泥对大肠杆菌的抗菌活性就很明显。上述结果表明 8SCPC-O 是治疗局部骨感染的良好候选药物。体外药物释放研究表明，与没有 Sr 取代的样品相比，8SCPC-O 样品中奥硝唑的释放加速。发现奥硝唑释放水泥与骨骼成肌细胞 (L6) 具有生物相容性。从第 1 天起，奥硝唑释放水泥对大肠杆菌的抗菌活性就很明显。上述结果表明 8SCPC-O 是治疗局部骨感染的良好候选药物。体外药物释放研究表明，与没有 Sr 取代的样品相比，8SCPC-O 样品中奥硝唑的释放加速。发现奥硝唑释放水泥与骨骼成肌细胞 (L6) 具有生物相容性。从第 1 天起，奥硝唑释放水泥对大肠杆菌的抗菌活性就很明显。上述结果表明 8SCPC-O 是治疗局部骨感染的良好候选药物。