Harnessing the Biomimetic Effect of Macromolecular Crowding in the Cell-Derived Model of Clubfoot Fibrosis

    August 2024 in “ Biomacromolecules
    Martina Doubková, Jarmila Knitlová, David Vondrášek, Adam Eckhardt, Tomáš Novotný, Martin Ošťádal, Elena Filová, Lucie Bačáková
    TLDR The model helps test drugs for clubfoot fibrosis by mimicking cell environments and shows minoxidil reduces harmful collagen links.
    This study presents a novel pseudo-3D in vitro model for high-throughput drug screening in pediatric clubfoot fibrosis, using clubfoot-derived fibroblasts and a biomimetic environment created by Ficoll and Polyvinylpyrrolidone to mimic macromolecular crowding. The model successfully increased collagen conversion and extracellular matrix formation, and upregulated fibrosis-related genes. Testing with the antifibrotic drug minoxidil showed it effectively blocked lysyl hydroxylases, reducing collagen cross-linking in fibrotic tissues. This model offers a valuable tool for preclinical research in clubfoot and similar fibroproliferative conditions.
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