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生物反应器中剪切应力作用下间充质干细胞在聚癸二酸山梨醇酯支架上的成骨分化

Osteogenic differentiation of mesenchymal stem cell on poly sorbitol sebacate scaffold under shear stress in a bioreactor.

作者信息

Abbasloo Fatemeh, Vahidi Bahman, Khani Mohammad-Mehdi, Sigaroodi Faraz, Sarbandi Reza Ramezani

机构信息

Department of Medical Technology and Tissue engineering, Faculty of Life Science Engineering, School of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran.

Department of Medical Technology and Tissue engineering, Faculty of Life Science Engineering, School of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran.

出版信息

Tissue Cell. 2025 Apr;93:102715. doi: 10.1016/j.tice.2024.102715. Epub 2025 Jan 2.

DOI:10.1016/j.tice.2024.102715
PMID:39787937
Abstract

Mechanical loading plays a pivotal role in regulating bone anabolic processes. Understanding the optimal mechanical loading parameters for cellular responses is critical for advancing strategies in orthopedic bioreactor-based bone tissue engineering. This study developed a poly (sorbitol sebacate) (PSS) filmscaffold with a sorbitol-to-sebacic acid molar ratio of 1:4. The scaffold underwent extensive characterization, including physical and mechanical property evaluations, biocompatibility assessments, and cell adhesion analysis. The Young's modulus of the PSS polymer was determined to be 6.81 ± 0.44 MPa under dry conditions, 6.37 ± 1.09 MPa in a wet state, and 6.38 ± 0.71 MPa after ethanol washing (70 %). The average contact angle of the PSS film was measured at 88.806 ± 1.644°, indicating moderate hydrophilicity. To investigate the osteogenic potential, a fluid flow inducing a shear stress of 1 Pa at a frequency of 1 Hz was applied to mesenchymal stem cells (MSCs) cultured on the PSS scaffold. Cells were exposed to dynamic fluid flow for one hour daily on days 4, 5, 6, and 7 of culture, followed by a static culture period of 14 days. The expression of osteogenic differentiation markers, including osteopontin (OPN), osteocalcin (OCN), type I collagen, and calcium deposition, was significantly elevated under dynamic conditions compared to static culture. This study highlights the importance of mechanical stimulation in enhancing MSC osteogenesis and underscores the osteoconductive properties of the PSS scaffold. These findings provide valuable insights into scaffold design and mechanical loading strategies for laboratory-based bone tissue engineering applications.

摘要

机械负荷在调节骨合成代谢过程中起着关键作用。了解细胞反应的最佳机械负荷参数对于推进基于骨科生物反应器的骨组织工程策略至关重要。本研究开发了一种山梨醇与癸二酸摩尔比为1:4的聚(癸二酸山梨醇酯)(PSS)薄膜支架。该支架进行了广泛的表征,包括物理和力学性能评估、生物相容性评估以及细胞粘附分析。PSS聚合物在干燥条件下的杨氏模量测定为6.81±0.44兆帕,在湿润状态下为6.37±1.09兆帕,在70%乙醇洗涤后为6.38±0.71兆帕。PSS薄膜的平均接触角测量为88.806±1.644°,表明具有中等亲水性。为了研究成骨潜力,对培养在PSS支架上的间充质干细胞(MSC)施加频率为1赫兹、剪切应力为1帕的流体流动。在培养的第4、5、6和7天,细胞每天暴露于动态流体流动1小时,随后进行14天的静态培养。与静态培养相比,在动态条件下,包括骨桥蛋白(OPN)、骨钙素(OCN)、I型胶原蛋白和成钙沉积在内的成骨分化标志物的表达显著升高。本研究强调了机械刺激在增强MSC成骨中的重要性,并强调了PSS支架的骨传导特性。这些发现为基于实验室的骨组织工程应用中的支架设计和机械负荷策略提供了有价值的见解。

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