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在芯片器官系统中构建生长因子梯度以驱动时空组织模式形成。

Engineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems.

作者信息

Hopkins Timothy, Midha Swati, Grossemy Simon, Screen Hazel R C, Wann Angus K T, Knight Martin M

机构信息

Centre for Predictive In Vitro Models, Queen Mary University of London, UK.

Centre for Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, UK.

出版信息

J Tissue Eng. 2025 Apr 18;16:20417314251326256. doi: 10.1177/20417314251326256. eCollection 2025 Jan-Dec.

DOI:10.1177/20417314251326256
PMID:40290860
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12033634/
Abstract

Spatial heterogeneity plays a key role in the development and function of human tissues and therefore needs to be incorporated within in vitro models to maximise physiological relevance and predictive power. Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats. The resulting BMP-2 gradient in 3D heparin methacryloyl/gelatin methacryloyl, successfully drove spatially divergent differentiation of human bone marrow-derived stem cells into bone-like and cartilage-like regions, mimicking the process of endochondral ossification in the growth plate. The application of hydrogel-embedded morphogens to drive spatial tissue patterning within OOAC systems represents a significant technological advancement and has broad-ranging applicability for a diverse range of tissues and organs, and a wide variety of OOAC platforms.

摘要

空间异质性在人体组织的发育和功能中起着关键作用，因此需要纳入体外模型中，以最大限度地提高生理相关性和预测能力。在此，我们开发并优化了方法，以在芯片器官（OOAC）系统中产生水凝胶包埋的生物活性信号分子的空间异质性，通过控制干细胞分化来驱动时空组织图案化。作为一个示例性应用，我们在封闭通道和开放腔室的OOAC形式中对骨形态发生蛋白-2（BMP-2）进行了空间图案化。在三维甲基丙烯酸肝素/甲基丙烯酸明胶中形成的BMP-2梯度成功地驱动了人骨髓来源干细胞在空间上分化为骨样和软骨样区域，模拟了生长板中的软骨内骨化过程。将水凝胶包埋的形态发生素应用于在OOAC系统中驱动空间组织图案化代表了一项重大的技术进步，并且对各种组织和器官以及各种各样的OOAC平台具有广泛的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/6a4322b687a7/10.1177_20417314251326256-fig14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/518e989c9343/10.1177_20417314251326256-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/ee4d9ea2b380/10.1177_20417314251326256-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/55483f5644c0/10.1177_20417314251326256-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/f80d680278da/10.1177_20417314251326256-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/958cda11d380/10.1177_20417314251326256-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/90d212dd0038/10.1177_20417314251326256-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/e8ab7ad6398d/10.1177_20417314251326256-fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/67d46342656f/10.1177_20417314251326256-fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/6a4322b687a7/10.1177_20417314251326256-fig14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/518e989c9343/10.1177_20417314251326256-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/96c915cdd0be/10.1177_20417314251326256-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/1fa3bd21c869/10.1177_20417314251326256-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/8fb31746d0b6/10.1177_20417314251326256-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/042aadfd7341/10.1177_20417314251326256-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/e7e30beec4e9/10.1177_20417314251326256-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/ee4d9ea2b380/10.1177_20417314251326256-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/55483f5644c0/10.1177_20417314251326256-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/f80d680278da/10.1177_20417314251326256-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/958cda11d380/10.1177_20417314251326256-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/90d212dd0038/10.1177_20417314251326256-fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/e8ab7ad6398d/10.1177_20417314251326256-fig12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/67d46342656f/10.1177_20417314251326256-fig13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d56/12033634/6a4322b687a7/10.1177_20417314251326256-fig14.jpg

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