State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials , Beijing University of Chemical Technology , Beijing 100029 , P. R. China.
Department of Stomatology , Tianjin Medical University General Hospital , Tianjin 300052 , P. R. China.
ACS Appl Mater Interfaces. 2019 Aug 28;11(34):30596-30609. doi: 10.1021/acsami.9b10219. Epub 2019 Aug 15.
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 strontium-doped apatite is deposited onto the microspheres via biomineralization in strontium-containing simulated body fluid. Sustained release behaviors of both vancomycin and Sr ions are achieved. The microspheres exhibit strong antibacterial effect against , 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 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.
具有同时诱导骨再生和杀菌能力的生物材料受到需求，因为在临床治疗中，骨缺损面临严重感染的风险。为了满足这一需求，制备了多功能可生物降解微球，其中包含万古霉素提供抗菌活性和掺锶磷灰石提供骨相容性。此外，锶成分具有促进血管生成的活性，这进一步有利于成骨。为了制备微球，将万古霉素载入介孔硅中，并通过双重乳液技术将其嵌入基于聚乳酸的微球中，通过含锶模拟体液中的生物矿化将掺锶磷灰石沉积在微球上。实现了万古霉素和 Sr 离子的持续释放行为。微球对 表现出强烈的抗菌作用，同时表现出优异的细胞/组织相容性。分化研究证实，锶元素的引入增强了间充质基质细胞的血管生成和成骨表达。将微球皮下注射到兔子背部，证实了它们在诱导新血管生成和异位成骨方面的有效性。最后，通过 感染创建了感染兔股骨髁缺损模型，并注射了多功能微球，与未加载万古霉素的生物矿化微球相比，体内显示出显著的抗菌活性，并实现了有效的新骨形成。载万古霉素和锶的微球具有生物矿化、可注射和可生物降解的特点，由于其能够将多种功能集成到一个设计中，具有灵活性，因此在治疗感染性骨缺损方面具有很高的应用潜力。
