Perfusion directed 3D mineral formation within cell-laden hydrogels

Perfusion directed 3D mineral formation within cell-laden hydrogels
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充满细胞的水凝胶内灌注引导 3D 矿物质形成

DOI:
10.1088/1758-5090/aacb42
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发表时间:
2018
期刊:
影响因子:
9
通讯作者:
Soman, Pranav
Soman, Pranav
中科院分区:
工程技术1区
文献类型:
--
作者:
Sawyer, Stephen W;Shridhar, Shivkumar Vishnempet;Zhang, Kairui;Albrecht, Lucas D;Filip, Alex B;Horton, Jason A;Soman, Pranav

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尽管干细胞工程前景广阔且生物打印技术取得了新进展,但制造大规模骨组织支架的主要挑战之一是无法将营养物质灌注到整个厚结构中。在这里,我们报告了一种可扩展的方法,使用充满细胞的水凝胶和 3D 打印的牺牲聚合物的组合来创建厚的、可灌注的骨结构。将类成骨细胞 Saos-2 细胞封装在甲基丙烯酸明胶 (GelMA) 水凝胶内,并使用 3D 打印聚乙烯醇管来创建可灌注通道。使用定制的生物反应器直接通过通道灌注成骨介质,以诱导矿物质沉积,随后通过微 CT 进行定量。组织学染色用于验证灌注通道周围的矿物质沉积,而 COMSOL 建模用于模拟相邻通道之间的氧气扩散。该信息用于设计一个放大的构建体,其中包含充满细胞的 GelMA 内的可灌注通道的 3D 阵列。通过灌注通道周围的细胞观察到渐进的基质矿化,而不是静态结构中的随机矿物质沉积。 Micro-CT 证实,灌注结构内的通道矿化与生物反应器内的时间之间存在直接关系。此外,这项工作中提出的可扩展方法可以作为如何使用常用的 3D 打印机、牺牲材料和水凝胶制造大规模骨组织替代结构的模型。
Despite the promise of stem cell engineering and the new advances in bioprinting technologies, one of the major challenges in the manufacturing of large scale bone tissue scaffolds is the inability to perfuse nutrients throughout thick constructs. Here, we report a scalable method to create thick, perfusable bone constructs using a combination of cell-laden hydrogels and a 3D printed sacrificial polymer. Osteoblast-like Saos-2 cells were encapsulated within a gelatin methacrylate (GelMA) hydrogel and 3D printed polyvinyl alcohol pipes were used to create perfusable channels. A custom-built bioreactor was used to perfuse osteogenic media directly through the channels in order to induce mineral deposition which was subsequently quantified via micro-CT. Histological staining was used to verify mineral deposition around the perfused channels, while COMSOL modeling was used to simulate oxygen diffusion between adjacent channels. This information was used to design a scaled-up construct containing a 3D array of perfusable channels within cell-laden GelMA. Progressive matrix mineralization was observed by cells surrounding perfused channels as opposed to random mineral deposition in static constructs. Micro-CT confirmed that there was a direct relationship between channel mineralization within perfused constructs and time within the bioreactor. Furthermore, the scalable method presented in this work serves as a model on how large-scale bone tissue replacement constructs could be made using commonly available 3D printers, sacrificial materials, and hydrogels.
DOI: 10.1002/bit.22361
发表时间: 2009-07-01
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发表时间: 2018
影响因子: 1.4
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