Tunable Mesoscopic Collagen Island Architectures Modulate Stem Cell Behavior.
Tunable Mesoscopic Collagen Island Architectures Modulate Stem Cell Behavior.
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可调节介观胶原岛结构调节干细胞行为。
DOI：
10.1002/adma.202207882
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Mak,Michael
中科院分区：
文献类型：
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作者：
Nguyen,RyanY;Cabral,AidanT;Rossello-Martinez,Alejandro;Zulli,Alessandro;Gong,Xiangyu;Zhang,Qiuting;Yan,Jing;Mak,Michael
细胞外基质是支撑哺乳动物细胞的生物物理环境。其主要成分是胶原蛋白。在生理组织中，胶原蛋白网络拓扑结构多样，具有复杂的介观特征。虽然研究已经探索了胶原蛋白密度和硬度的作用，但复杂结构的影响仍未得到很好的理解。开发能够概括这些不同胶原结构的体外系统对于理解生理相关的细胞行为至关重要。在这里，开发了方法来诱导形成异质介观结构，被称为胶原岛，在胶原水凝胶。这些含岛凝胶具有高度可调的内含物和机械性能。虽然这些凝胶在整体上是柔软的，但在细胞尺度上胶原蛋白浓度存在区域富集。胶原岛结构被用于研究间充质干细胞的行为，并证明细胞迁移和成骨分化被改变。最后，将诱导多能干细胞培养在含岛凝胶中，结果表明这种结构足以诱导中胚层分化。总的来说，这项工作强调了复杂的介观组织结构作为调节细胞行为的生物活性线索，并提出了一种新型的胶原基水凝胶，该凝胶可以捕获组织工程应用的这些特征。
The extracellular matrix is the biophysical environment that scaffolds mammalian cells in the body. The main constituent is collagen. In physiological tissues, collagen network topology is diverse with complex mesoscopic features. While studies have explored the roles of collagen density and stiffness, the impact of complex architectures remains not well‐understood. Developing in vitro systems that recapitulate these diverse collagen architectures is critical for understanding physiologically relevant cell behaviors. Here, methods are developed to induce the formation of heterogeneous mesoscopic architectures, referred to as collagen islands, in collagen hydrogels. These island‐containing gels have highly tunable inclusions and mechanical properties. Although these gels are globally soft, there is regional enrichment in the collagen concentration at the cell‐scale. Collagen‐island architectures are utilized to study mesenchymal stem cell behavior, and it is demonstrated that cell migration and osteogenic differentiation are altered. Finally, induced pluripotent stem cells are cultured in island‐containing gels, and it is shown that the architecture is sufficient to induce mesodermal differentiation. Overall, this work highlights complex mesoscopic tissue architectures as bioactive cues in regulating cell behavior and presents a novel collagen‐based hydrogel that captures these features for tissue engineering applications.