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Vancomycin- and Strontium-Loaded Microspheres with Multifunctional Activities in Antibacteria, Angiogenesis and Osteogenesis for Enhancing Infected Bone Regeneration.

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Biomaterials that simultaneously have capacities in inducing bone regeneration and in killing bacteria, are in demand when bone defects face risks of severe infection in clinical therapy. To meet the… Click to show full abstract

Biomaterials that simultaneously have capacities in inducing bone regeneration and in killing bacteria, are in demand when bone defects face risks of severe infection in clinical therapy. To meet the demand, a kind of multifunctional biodegradable microspheres are fabricated, which contain vancomycin to provide anti-bacterial activity, and contain strontium-doped apatite to provide osteocompatibility. Moreover, the strontium component shows activity in promoting angiogenesis, which further favors osteogenesis. In producing the microspheres, vancomycin is loaded into mesoporous silica and embedded in polylactide-based microspheres via the double emulsion technique, and the strontium-doped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr2+ ion are achieved. The microspheres exhibit strong antibacterial effect against S.aureus, while demonstrate 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 back confirms their effectiveness in inducing neovascularization and ectopic osteogenesis. Finally, infected rabbit femoral condyle defect model is created with S.aureus infection and the multifunctional microspheres are injected, displaying 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 for their flexibility in integrating multifunction into one design, whose potentials in treating infected bone defects are highly expected.

Keywords: loaded microspheres; bone regeneration; vancomycin strontium; strontium loaded; bone; strontium

Journal Title: ACS applied materials & interfaces
Year Published: 2019

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