Dual-Controlled Release of Icariin/Mg2+ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration.
Published on Apr 27, 2020in Advanced Healthcare Materials7.367
· DOI :10.1002/ADHM.202000211
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., Mg(2+) ), 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 Mg(2+) 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 Mg(2+) 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.