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Polycaprolactone scaffold engineered for sustained release of resveratrol: therapeutic enhancement in bone tissue engineering

机译:聚己内酯支架设计用于白藜芦醇的持续释放:增强骨组织工程的治疗

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摘要

Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycapro-lactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering.
机译:基于生物材料的三维支架正在骨组织工程中得到广泛研究。潜在的支架应具有骨传导性,骨诱导性和成骨性,以增强骨骼形成。在这项研究中,三维多孔聚己内酯(PCL)支架被设计为白藜芦醇的延长释放。合成了负载白藜芦醇的白蛋白纳米颗粒(RNP),并通过溶剂浇铸和浸出法将其包埋在PCL支架中以形成PCL-RNP。对RNP和PCL-RNP的X射线衍射研究表明,白藜芦醇进行了非晶化,这在药物递送中是非常需要的。此外,傅立叶变换红外光谱表明白藜芦醇在包封过程中没有化学修饰。持续从PCL-RNP释放白藜芦醇,在第12天结束时累积释放64%。使用人类骨髓来源的间充质干细胞体外评估支架在16天的成骨潜能。与PCL支架(阳性对照)相比,在第8天和第12天测定的碱性磷酸酶活性显示出PCL-RNP诱导的活性显着增加(分别为1.6倍和1.4倍)。此外,第16天的von Kossa钙沉积染色显示PCL-RNP中矿化增加。这些结果表明,由于PCL-RNP可以控制并延长白藜芦醇的释放,因此可显着改善矿化作用,从而增加了骨组织工程的治疗潜力。

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