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通过嵌入辛伐他汀增强聚(乳酸-共-乙醇酸)和双相陶瓷支架的成骨能力。

Enhanced osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds by embedding simvastatin.

机构信息

Department of Dentistry, Center for Research On Dental Implants (CEPID), Federal University of Santa Catarina, Florianopolis, Brazil.

Department of Microbiology, Immunology, and Parasitology, Laboratory of Applied Virology (LVA), Federal University of Santa Catarina, Florianopolis, Brazil.

出版信息

Clin Oral Investig. 2022 Mar;26(3):2693-2701. doi: 10.1007/s00784-021-04240-9. Epub 2021 Oct 25.

Abstract

OBJECTIVES

This study evaluated the effect of embedding simvastatin (SIM) on the osteoinductive capacity of PLGA + HA/βTCP scaffolds in stem cells from human exfoliated deciduous teeth (SHED).

MATERIALS AND METHODS

Scaffolds were produced by PLGA solvent dissolution, addition of HA/βTCP, solvent evaporation, and leaching of sucrose particles to impart porosity. Biphasic ceramic particles (70% HA/30% βTCP) were added to the PLGA in a 1:1 (w:w) ratio. Scaffolds with SIM received 1% (w:w) of this medication. Scaffolds were synthesized in a disc-shape and sterilized by ethylene oxide. The experimental groups were (G1) PLGA + HA/βTCP and (G2) PLGA + HA/βTCP + SIM in non-osteogenic culture medium, while (G3) SHED and (G4) MC3T3-E1 in osteogenic culture medium were the positive control groups. The release profile of SIM from scaffolds was evaluated. DNA quantification assay, alkaline phosphatase activity, osteocalcin and osteonectin proteins, extracellular calcium detection, von Kossa staining, and X-ray microtomography were performed to assess the capacity of scaffolds to induce the osteogenic differentiation of SHED.

RESULTS

The release profile of SIM followed a non-liner sustained-release rate, reaching about 40% of drug release at day 28. Additionally, G2 promoted the highest osteogenic differentiation of SHED, even when compared to the positive control groups.

CONCLUSIONS

In summary, the osteoinductive capacity of poly(lactic-co-glycolic) acid and biphasic ceramic scaffolds was expressively enhanced by embedding simvastatin.

CLINICAL RELEVANCE

Bone regeneration is still a limiting factor in the success of several approaches to oral and maxillofacial surgeries, though tissue engineering using mesenchymal stem cells, scaffolds, and osteoinductive mediators might collaborate to this topic.

摘要

目的

本研究评估了辛伐他汀(SIM)包埋对人乳牙牙髓干细胞(SHED)来源的 PLGA+HA/βTCP 支架成骨能力的影响。

材料和方法

支架通过 PLGA 溶剂溶解、添加 HA/βTCP、溶剂蒸发和蔗糖颗粒浸出来赋予多孔性来制备。双相陶瓷颗粒(70%HA/30%βTCP)以 1:1(w/w)的比例添加到 PLGA 中。SIM 接收 1%(w/w)的这种药物的支架。支架以圆盘形状合成并通过环氧乙烷灭菌。实验组为(G1)PLGA+HA/βTCP 和(G2)PLGA+HA/βTCP+SIM 在非成骨培养基中,而(G3)SHED 和(G4)MC3T3-E1 在成骨培养基中为阳性对照组。评估 SIM 从支架中的释放情况。进行 DNA 定量测定、碱性磷酸酶活性、骨钙素和骨连蛋白蛋白、细胞外钙检测、von Kossa 染色和 X 射线微断层扫描,以评估支架诱导 SHED 成骨分化的能力。

结果

SIM 的释放曲线遵循非线性持续释放率,在第 28 天达到约 40%的药物释放。此外,与阳性对照组相比,G2 促进了 SHED 的最高成骨分化。

结论

总之,通过包埋辛伐他汀,显著增强了聚(乳酸-共-乙醇酸)和双相陶瓷支架的成骨能力。

临床相关性

尽管使用间充质干细胞、支架和成骨诱导介质的组织工程可能有助于解决口腔颌面外科的许多方法中的骨再生仍然是一个限制因素。

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