Treatment of infected bone defects still remains a formidable clinical challenge, and the design of bone implants with both anti-bacterial activity and osteogenesis effects is nowadays regarded as a powerful strategy for infection control and bone healing.
Biomaterials that have capacities to simultaneously induce bone regeneration and kill bacteria are in demand because bone defects face risks of severe infection in clinical therapy. To meet the demand, multifunctional biodegradable microspheres are fabricated, which contain vancomycin to provide antibacterial activity and strontium-doped apatite to provide osteocompatibility. Moreover, the strontium component shows activity in promoting angiogenesis, which further favors osteogenesis. For producing the microspheres, vancomycin is loaded into mesoporous silica and embedded in polylactide-based microspheres via the double emulsion technique and the strontiumdoped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr 2+ ions are achieved. The microspheres exhibit strong antibacterial effect against Staphylococcus aureus, while demonstrating excellent cell/tissue compatibility. Studies of differentiation confirm that the introduction of strontium element strengthens the angiogenic and osteogenic expressions of mesenchymal stromal cells. Subcutaneous injection of the microspheres into rabbit's back confirms their effectiveness in inducing neovascularization and ectopic osteogenesis. Finally, an infected rabbit femoral condyle defect model is created with S. aureus infection and the multifunctional microspheres are injected, which display significant antibacterial activity in vivo and achieve efficient new bone formation in comparison with biomineralized microspheres without vancomycin loading. The vancomycin-and strontium-loaded microspheres, being biomineralized, injectable, and biodegradable, are attractive because of their flexibility in integrating multiple functions into one design, whose potentials in treating infected bone defects are highly expected.
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.
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