Master thesis defense Emmie Schoutens
On Thursday 12 October, BiS master student Emmie Schoutens will defend her thesis on the role of stent strut architecture on 3D tissue formation. If you are interested in this topic, you can click on the “continue reading”button.
Stent angioplasty is commonly used to treat occluded heart blood vessels, but many patients suffer from in-stent restenosis (ISR), a second lumen narrowing. Stents induce mechanical cues during several stages of the ISR process, for example actively during stent deployment or passively by strut design. This study investigated this influence of mechanical cues on cellular proliferation as a crucial factor in understanding ISR tissue formation and optimizing stent design. First, passive stress, as implied by stent strut design, was researched by culturing fibroblasts on polydimethylsiloxane (PDMS) chips with various geometrical features. Experiments revealed that shapes with sharp corners induced significantly higher levels of cell proliferation and actin intensity compared to smooth, rounder shapes. These findings were validated in both 2D (cell monolayer) and 3D (cell-embedded hydrogel) setups. ROCK inhibitor Y-26732 effectively disrupted the observed effects, confirming mechanical stress and strain as the underlying mechanism for the proliferation patterns. This correlation between mechanical strain and proliferation was further researched by a simplified experimental setup, using active stresses as an inductive cue. Finite element simulations and Digital Image Correlation were used to predict and validate strain patterns in uniaxially stretched rectangular and tapered substrates. It was observed that rectangular samples yield a homogeneous strain field, whereas the tapered samples demonstrate an increasing strain magnitude over the length of the sample. Fibroblast culture on both types of substrates exhibited increased cell proliferation when stretch is applied. No increase in proliferation was found between uniform stretch magnitudes 2%, 10% and 20%, or over the length of the tapered sample stretched to 5%. For the 10% tapered stretch conditions, proliferation seemed to increase with increasing strain magnitude. Addition of Y-26732 nullified this effect. Overall, this research has established experimental platforms to research cellular mechanisms to both passively and actively induced cell stresses, but future studies need to focus on expanding sample sizes to obtain statistically significant results. Ultimately, this research contributes to the understanding of the complex mechanobiological processes that drive ISR tissue formation and offer potential for improving stent design in the future.