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Ahn, Seungkuk; Jain, Akanksha; Kasuba, Krishna Chaitanya; Seimiya, Makiko; Okamoto, Ryoko; Treutlein, Barbara; Müller, Daniel J.
Biomaterials, July 2024, 2024-Jul, 2024-07-00, 20240701, Letnik: 308Journal Article
Cells assemble fibronectin, the major extracellular matrix (ECM) protein, into fibrillar matrices, which serve as 3D architectural scaffolds to provide, together with other ECM proteins tissue-specific environments. Although recent approaches enable to bioengineer 3D fibrillar fibronectin matrices in vitro, it remains elusive how fibronectin can be co-assembled with other ECM proteins into complex 3D fibrillar matrices that recapitulate tissue-specific compositions and cellular responses. Here, we introduce the engineering of fibrillar fibronectin-templated 3D matrices that can be complemented with other ECM proteins, including vitronectin, collagen, and laminin to resemble ECM architectures observed in vivo. For the co-assembly of different ECM proteins, we employed their innate fibrillogenic mechanisms including shear forces, pH-dependent electrostatic interactions, or specific binding domains. Through recapitulating various tissue-specific ECM compositions and morphologies, the large scale multi-composite 3D fibrillar ECM matrices can guide fibroblast adhesion, 3D fibroblast tissue formation, or tissue morphogenesis of epithelial cells. In other examples, we customize multi-composite 3D fibrillar matrices to support the growth of signal propagating neuronal networks and of human brain organoids. We envision that these 3D fibrillar ECM matrices can be tailored in scale and composition to modulate tissue-specific responses across various biological length scales and systems, and thus to advance manyfold studies of cell biological systems. Display omitted •We engineer 3D multi-composite fibrillar ECMs of well-defined compositions of key ECM proteins (including fibronectin, laminin, collagen, or vitronectin) such as needed by various tissues.•The multi-composite ECMs are free-standing, easy-to-produce, scalable, transferable for surface functionalization, and mimic the nano-and micro-fibrillar architecture of native ECMs.•The multi-composite ECMs can evoke cellular responses across various biological and temporal scales, from single cells to complex multicellular structures like tissues or organoids, spanning from initial cell attachment to extended culture periods of weeks.
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