Dual-Controlled Release of Icariin/Mg²⁺ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on...

Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere-type scaffolds are designed to achieve the dual-controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg²⁺ ), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO₃ (1:1 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg²⁺ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI-M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI-M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO₃ but without icariin) and blank PLGA microspheres. Clearly, the released Mg²⁺ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual-release system.