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Mesenchymal Stem Cell Interactions with 3D ECM Modules Fabricated via Multiphoton Excited Photochemistry

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Department of Biomedical Engineering, §Laboratory for Optical and Computational Instrumentation, Materials Science Program, #Medical Physics Department, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States
Cite this: Biomacromolecules 2012, 13, 9, 2917–2925
Publication Date (Web):August 9, 2012
https://doi.org/10.1021/bm300949k
Copyright © 2012 American Chemical Society
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Abstract

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To understand complex micro/nanoscale ECM stem cell interactions, reproducible in vitro models are needed that can strictly recapitulate the relative content and spatial arrangement of native tissue. Additionally, whole ECM proteins are required to most accurately reflect native binding dynamics. To address this need, we use multiphoton excited photochemistry to create 3D whole protein constructs or “modules” to study how the ECM governs stem cell migration. The constructs were created from mixtures of BSA/laminin (LN) and BSA alone, whose comparison afforded studying how the migration dynamics are governed from the combination of morphological and ECM cues. We found that mesenchymal stem cells interacted for significantly longer durations with the BSA/LN constructs than pure BSA, pointing to the importance of binding cues of the LN. Critical to this work was the development of an automated system with feedback based on fluorescence imaging to provide quality control when synthesizing multiple identical constructs.

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Video 1: Time-lapse phase contrast videos also showed MSCs migrating toward, around and within the 3D environment. Video 2: Time-lapse phase contrast videos also showed MSCs interacting with the module, with each other, and undergoing mitosis. Video 3: Time-lapse phase contrast videos also showed MSCs physically deforming the module. This material is available free of charge via the Internet at http://pubs.acs.org.

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