Mesoporous Silicon-PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering
Mesoporous Silicon-PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering
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DOI：
10.1002/adfm.201100403
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发表时间：
2012-01-25
影响因子：
19
通讯作者：
Tasciotti, Ennio
中科院分区：
文献类型：
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作者：
Fan, Dongmei;De Rosa, Enrica;Tasciotti, Ennio
在这项研究中，聚（DL-丙交酯-共-乙交酯）/多孔硅（PLGA/pSi）复合微球，通过固体-油-水（S/O/W）乳液法合成，开发用于骨科组织工程应用的生物分子的长期控制输送。共聚焦和荧光显微镜，连同材料分析，显示每个复合微球包含多个pSi颗粒嵌入在PLGA基质。异硫氰酸荧光素（FITC）标记的牛血清白蛋白（FITC-BSA），内的PLGA基质内的pSi内加载的释放曲线表明，PLGA和pSi有助于控制有效载荷的释放速率。蛋白质稳定性研究表明，PLGA/pSi复合材料可以保护BSA在长期释放过程中不被降解。我们发现，在复合材料的降解过程中，pSi颗粒的存在中和了由于PLGA降解副产物引起的酸性pH，从而最大限度地降低了在暴露细胞中诱导炎症反应的风险，同时刺激了成骨生长培养基中的矿化。共聚焦研究表明，避免了复合微球的细胞摄取，而荧光有效载荷在共孵育7天后可在细胞内检测到。总之，PLGA/pSi复合微球提供了一个额外的水平的控制释放，并可能是理想的候选人作为药物递送载体的骨科组织工程应用。
In this study, poly(dl-lactide-co-glycolide)/porous silicon (PLGA/pSi) composite microspheres, synthesized by a solid-in-oil-in-water (S/O/W) emulsion method, are developed for the long-term controlled delivery of biomolecules for orthopedic tissue engineering applications. Confocal and fluorescent microscopy, together with material analysis, show that each composite microsphere contained multiple pSi particles embedded within the PLGA matrix. The release profiles of fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA), loaded inside the pSi within the PLGA matrix, indicate that both PLGA and pSi contribute to the control of the release rate of the payload. Protein stability studies show that PLGA/pSi composite can protect BSA from degradation during the long term release. We find that during the degradation of the composite material, the presence of the pSi particles neutralizes the acidic pH due to the PLGA degradation by-products, thus minimizing the risk of inducing inflammatory responses in the exposed cells while stimulating the mineralization in osteogenic growth media. Confocal studies show that the cellular uptake of the composite microspheres is avoided, while the fluorescent payload is detectable intracellularly after 7 days of co-incubation. In conclusion, the PLGA/pSi composite microspheres offer an additional level of controlled release and could be ideal candidates as drug delivery vehicles for orthopedic tissue engineering applications.