Microstructure and properties of alendronate-loaded calcium phosphate cement

• The effects of alendronate (ALN) on the properties of CPC were dose-dependent.
• The setting time of CPC was prolonged by the addition of alendronate.
• The injectability was dramatically improved by the addition of alendronate.
• The porosity of the hydrated CPC decreased with the addition of alendronate.
• The ALN-induced densification of CPC increased the compressive strength of CPC.

Calcium phosphate cement (CPC), as an injectable bone substitute material is significant in bone defect treatment. Drugs and biological molecules are often incorporated into CPC to promote the healing of bone defects and treat some bone diseases. In this work, alendronate (ALN)-loaded CPC was prepared and the influences of the content of ALN on the setting time, microstructure of hydrate porosity, mechanical strength, in vitro drug release, rheological properties and injectability of CPC were systematically investigated. The results showed that the addition of ALN had no effect on the final hydration product of CPC. The setting time of CPC was prolonged, while the prolonging effect became weak when the larger amount of ALN was added. With the increment of ALN content, the hydroxyapatite crystals of cured CPC became smaller, and the hydrated CPC became more compact with lower porosity, which resulted in the improvement of compressive strength of CPC with a drug-loaded amount less than 1 wt%. The injectability was dramatically improved due to the addition of ALN, which was corresponding to the decrease of viscosity. The thixotropy of the CPC slurry was promoted with increasing the ALN content, which could enhance the stability of the slurry. However, it was worth noting that an inverted thixotropic loop appeared when the drug content was higher than 3.0 wt%. During the in vitro drug release, the initial burst release turned up for all formulations and the degree of burst release was different from each other. This work would allow advances in understanding the effect of ALN on the setting process and physical and chemical properties of CPC, and we should think over the appropriate content when adding ALN into CPC.