Vancomycin- and Strontium-Loaded Microspheres with Multifunctional Activities against Bacteria, in Angiogenesis, and in Osteogenesis for Enhancing Infected Bone Regeneration
Vancomycin- and Strontium-Loaded Microspheres with Multifunctional Activities against Bacteria, in Angiogenesis, and in Osteogenesis for Enhancing Infected Bone Regeneration
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负载万古霉素和锶的微球具有抗菌、血管生成和骨生成等多功能活性，可增强感染骨再生
DOI：
10.1021/acsami.9b10219
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发表时间：
2019-08-28
影响因子：
9.5
通讯作者：
Yang, Xiaoping
中科院分区：
文献类型：
--
作者：
Wei, Pengfei;Jing, Wei;Yang, Xiaoping
由于骨缺损在临床治疗中面临严重感染的风险，因此需要能够同时诱导骨再生和杀死细菌的生物材料。为了满足这一需求，制备了多功能生物可降解微球，其中包含万古霉素以提供抗菌活性和掺锶磷灰石以提供骨相容性。此外，锶组分显示出促进血管生成的活性，这进一步有利于骨生成。为了制备微球，万古霉素被装载到介孔二氧化硅中，并通过双乳液技术包埋在聚乳酸基微球中，并且掺锶磷灰石通过在含锶的模拟体液中的生物矿化沉积到微球上。实现了万古霉素和Sr 2+离子的持续释放行为。该微球对金黄色葡萄球菌表现出强的抗菌作用，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背部证实了其诱导新血管形成和异位成骨的有效性。最后用S.金黄色葡萄球菌感染，并且注射多功能微球，与没有万古霉素负载的生物矿化微球相比，其在体内显示出显著的抗菌活性并实现有效的新骨形成。载万古霉素和锶的微球是生物矿化的、可注射的和可生物降解的，由于其将多种功能整合到一个设计中的灵活性而具有吸引力，其在治疗感染性骨缺损方面的潜力是高度期望的。
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 Sr2+ 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.