Reyes-Ramos, Ana M.

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    Effects of collagen matrix architecture in different biomedical applications
    (2020-07-24) Reyes-Ramos, Ana M.; Domenech, Maribella; College of Engineering; Almodóvar-Montanez, Jorge; Torres-Lugo, Madeline; Ortíz-Bermúdez, Patricia; Department of Chemical Engineering; Perales-Pérez, Oscar J.
    The extracellular matrix (ECM) is one critical component of the tissue microenvironment that regulates many cellular functions, providing biochemical and biomechanical cues for tissue development and function. Collagen is one of the most abundant components of the ECM, where several studies have shown that changes to the collagen matrix architecture are hallmarks of cancer progression and cell differentiation. As such, the identification and integration of ECM components is critical for assessment of cell function and modeling of diseases using in vitro models, the closer we can mimic these environments in vitro, the higher the likelihood of predicting cell function and responses observed in vivo. Several physical parameters of the ECM have been shown to impact cell behavior. The fibrous architecture and organization are one of the least represented structural aspects of the ECM in culture platforms. One of the limitations of integrating fibrous network matrix into in vitro model is precisely controlling key parameters that modulate cell adhesion, migration, and differentiation, such as fiber orientation, porosity, diameter, and stiffness. In this project, to tackle these challenges we developed and characterized collagen I fibrous substrates of defined orientation with specific diameter, stiffness, and porosity, for culture applications. The impact of these substrates was examined at the cell level in the following models: i) hormone-independent growth of breast cancer cells, ii) Hedgehog (Hh) signaling pathway activity in mesenchymal cells, and iii) cell differentiation and potency of induced-Pluripotent stem cell (iPSCs Electrospinning process was optimized, obtaining collagen fibers with random and aligned orientation, with similar diameter and stiffness. In vitro experiments of MCF-7 and T-47D cells cultured in collagen fibers showed hormone-independent growth that was driven by a cell-matrix signal such α2β1 integrin. Interactions of Adipose Mesenchymal Stem Cells with collagen fibers decreased tumor growth, opposite behavior with the presence of Fibroblasts, therefore, fibroblasts area determinant factor to increase proliferation of Triple-Negative Breast Cancer. In cardiac studies, Collagen fibers with fibronectin coating generate the best outcomes with the highest percentage of the differentiated and mature cardiomyocytes. In general, results highlight that cells can perceive changes in the structure and orientation of collagen fibers and support the use of these substrates for prototyping of culture platforms.