Highly Stable Amorphous (Pyro)phosphate Aggregates: Pyrophosphate as a Carrier for Bioactive Ions and Drugs in Bone...

Pyrophosphate is widely used as an iron supplement because of its excellent complexation and hydrolysis ability; however, there are few reports on the use of pyrophosphate in active ionophores for bone repair. In this research, we proposed a simple and efficient ultrasonic method to prepare magnesium-calcium (pyro)phosphate aggregates (AMCPs). Due to strong hydration, AMCPs maintain a stable amorphous form even at high temperatures (400 °C). By changing the molar ratio of calcium and magnesium ions, the content of calcium and magnesium ions can be customized. AMCPs had surface negativity and complexing ability that realized the controlled release of ions (Ca²⁺, Mg²⁺, and P) and drugs (such as doxorubicin) over a long period. Pyrophosphate gave it an excellent bacteriostatic effect. Increasingly released Mg²⁺ exhibited improved bioactivity though the content of Ca²⁺ decreased. While Mg²⁺ content was regulated to 15 wt %, it performed significantly enhanced stimulation on the proliferation, attachment, and differentiation (ALP activity, calcium nodules, and the related gene expression of osteogenesis) of mouse embryo osteoblast precursor cells (MC3T3-E1). Furthermore, the high content of Mg²⁺ also effectively promoted the proliferation, attachment, and migration of human umbilical vein endothelial cells (HUVECs) and the expression of angiogenic genes. In conclusion, pyrophosphate was an excellent carrier for bioactive ions, and the AMCPs we prepared had a variety of active functions for multiscenario bone repair applications.