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熔融静电纺丝制备的纤维支架中孔径对人骨髓间充质干细胞成骨的影响。

The effect of pore size within fibrous scaffolds fabricated using melt electrowriting on human bone marrow stem cell osteogenesis.

机构信息

Dept. of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Ireland. Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.

出版信息

Biomed Mater. 2019 Nov 8;14(6):065016. doi: 10.1088/1748-605X/ab49f2.

Abstract

Limitations associated with current bone grafting materials has necessitated the development of synthetic scaffolds that mimic the native tissue for bone repair. Scaffold parameters such as pore size, pore interconnectivity, fibre diameter, and fibre stiffness are crucial parameters of fibrous bone tissue engineering (BTE) scaffolds required to replicate the native environment. Optimum values vary with material, fabrication method and cell type. Melt electrowriting (MEW) provides precise control over extracellular matrix (ECM)-like fibrous scaffold architecture. The goal of this study was to fabricate and characterise poly-ε-caprolactone (PCL) fibrous scaffolds with 100, 200, and 300 μm pore sizes using MEW and determine the influence of pore size on human bone marrow stem cell (hMSC) adhesion, morphology, proliferation, mechanosignalling and osteogenesis. Each scaffold was fabricated with a fibre diameter of 4.01 ± 0.06 μm. The findings from this study highlight the enhanced osteogenic effects of controlled micro-scale fibre deposition using MEW, where the benefits of 100 μm square pores in comparison with larger pore sizes are illustrated, a pore size traditionally reported as a lower limit for osteogenesis. This suggests a lower pore size is optimal when hMSCs are seeded in a 3D ECM-like fibrous structure, with the 100 μm pore size optimal as it demonstrates the highest global stiffness, local fibre stiffness, highest seeding efficiency, maintains a spread cellular morphology, and significantly enhances hMSC collagen and mineral deposition. Similarly, this platform represents an effective in vitro model for the study of hMSC behaviour to determine the significant osteogenic benefits of controlling ECM-like fibrous BTE scaffold pore size using MEW.

摘要

当前骨移植物材料的局限性使得人们有必要开发出模仿天然组织的合成支架来进行骨修复。支架参数(如孔径、孔连通性、纤维直径和纤维刚度)是纤维状骨组织工程(BTE)支架的关键参数,这些参数对于复制天然环境至关重要。最佳值因材料、制造方法和细胞类型而异。熔融静电纺丝(MEW)可对类似于细胞外基质(ECM)的纤维状支架结构进行精确控制。本研究的目的是使用 MEW 制造和表征具有 100、200 和 300 μm 孔径的聚己内酯(PCL)纤维状支架,并确定孔径对人骨髓间充质干细胞(hMSC)黏附、形态、增殖、机械信号转导和成骨的影响。每个支架的纤维直径均为 4.01±0.06 μm。本研究的结果强调了使用 MEW 进行受控微尺度纤维沉积对成骨的增强作用,其中,与较大孔径相比,100 μm 方形孔的优势得到了说明,而传统上认为较大孔径是成骨的下限。这表明,当 hMSC 接种在 3D 类似于 ECM 的纤维状结构中时,较小的孔径是最佳的,因为 100 μm 的孔径可表现出最高的整体刚度、局部纤维刚度、最高的接种效率、保持细胞形态的扩展,并显著增强 hMSC 胶原蛋白和矿物质沉积。同样,该平台代表了一种有效的体外模型,可用于研究 hMSC 行为,以确定使用 MEW 控制类似于 ECM 的 BTE 支架孔径对成骨的重要益处。

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