Browsing by Subject "Mechanotransduction"

Now showing 1 - 2 of 2
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    Bioreactor Conditioning for Accelerated Remodeling of Fibrin-Based Tissue Engineered Heart Valves
    (2015-05) Schmidt, Jillian
    Fibrin is a promising scaffold material for tissue engineered heart valves, as it is completely biological, allows for engineered matrix alignment, and is able to be degraded and replaced with collagen by entrapped cells. However, the initial fibrin matrix is mechanically weak, and extensive in vitro culture is required to create valves with sufficient mechanical strength and stiffness for in vivo function. Culture in bioreactor systems, which provide cyclic stretching and enhance nutrient transport, has been shown to increase collagen production by cells entrapped in a fibrin scaffold, accelerating strengthening of the tissue and reducing the required culture time. In the present work, steps were taken to improve bioreactor culture conditions with the goal of accelerating collagen production in fibrin-based tissue engineered heart valves using two approaches: (i) optimizing the cyclic stretching protocol and (ii) developing a novel bioreactor system that permits transmural and lumenal flow of culture medium for improved nutrient transport. The results indicated that incrementally increasing strain amplitude cyclic stretching with small, frequent increments in strain amplitude was optimal for collagen production in our system. In addition, proof of concept studies were performed in the novel bioreactor system and increased cellularity and collagen deposition near the lumenal surface of the tissue were observed.
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    Differential biophysical mechanisms driving cancer stem cell migration
    (2022-01) Heussner, Rachel
    Cancer stem cells (CSCs) are known to have a high capacity for tumor initiation and are likely a key player in the formation of metastases. We have previously shown that in aligned collagen constructs similar to in vivo structures indicative of disease progression, breast CSCs demonstrate enhanced directional and total motility compared to the carcinoma population as a whole (WP). Here, we show that increased motility is maintained by CSCs in diverse environments including elastic, nonaligned 2D polyacrylamide gels at various stiffness; 3D randomly oriented collagen matrices; and ectopic cerebral slices representative of common metastatic sites. The consistency of CSCs’ enhanced motility across diverse environments suggests a general shift in cell migration mechanics between well differentiated carcinoma cells and their stem-like counterparts. To further elucidate the source of differences in migration, we demonstrate that CSCs are less contractile than the carcinoma population as a whole and concomitantly produce fewer and smaller focal adhesions. This shift in CSC biophysical behavior can be tuned via contractility. The WP can be shifted to a CSC-like enhanced migratory phenotype using partial myosin II inhibition. Inversely, CSCs can be shifted to a less migratory WP-like phenotype using microtubule destabilizing drugs to increase contractility. This work begins to elucidate the mechanistic differences driving CSC migration and raises important implications regarding the potentially disparate effects of microtubule-targeting agents on the motility of different cell populations.