Biodegradable magnesium and zinc composite microspheres with synergistic osteogenic effect for enhanced bone...

Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg²⁺ and a gradual release of Zn²⁺ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg²⁺ and Zn²⁺ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg²⁺ and Zn²⁺ have great potential in the delivery of therapeutic ions for treating bone defects.