Cyclical depressurization degranulates platelets in an agonist-free mechanism of platelet activation.

Activation of circulating platelets by receptor binding and subsequent coagulation events are defined by a well characterized physiological response. However, the growing prevalence of chronic kidney disease (CKD) and implication of platelet-released factors in worsening cardiovascular outcomes with hemodialysis warrant further investigation into the mechanobiology of platelet degranulation. The significant drops in pressure caused by high friction across the hemodialysis flow circuit present an overlooked platelet stimulant not involving immobilization as a driver for cytoskeletal rearrangement.

Hemodialysis exacerbates proteolytic imbalance and pro-fibrotic platelet dysfunction.

Multi-organ fibrosis among end stage renal disease (ESRD) patients cannot be explained by uremia alone. Despite mitigation of thrombosis during hemodialysis (HD), subsequent platelet dysfunction and tissue dysregulation are less understood. We comprehensively profiled plasma and platelets from ESRD patients before and after HD to examine HD-modulation of platelets beyond thrombotic activation.

Controlled Release of Small Molecules for Cardiac Differentiation of Pluripotent Stem Cells.

Induced pluripotent stem cells (iPSCs) have been shown to differentiate to functional cardiomyocytes (CM) with high efficiency through temporally controlled inhibition of the GSK3/Wnt signaling pathways. In this study, we investigated the ability of temporally controlled release of GSK3/Wnt small-molecule inhibitors to drive cardiac differentiation of iPSC without manual intervention. Porous silica particles were loaded with GSK3 inhibitor CHIR99021 or Wnt inhibitor IWP2, and the particles containing IWP2 were coated with 5 wt% poly(lactic-co-glycolic acid) 50:50 to delay release by ∼72 h.

Differentiation of spontaneously contracting cardiomyocytes from non-virally reprogrammed human amniotic fluid stem cells.

Congenital heart defects are the most common birth defect. The limiting factor in tissue engineering repair strategies is an autologous source of functional cardiomyocytes. Amniotic fluid contains an ideal cell source for prenatal harvest and use in correction of congenital heart defects.

Discrete quasi-linear viscoelastic damping analysis of connective tissues, and the biomechanics of stretching.

The time- and frequency-dependent properties of connective tissue define their physiological function, but are notoriously difficult to characterize. Well-established tools such as linear viscoelasticity and the Fung quasi-linear viscoelastic (QLV) model impose forms on responses that can mask true tissue behavior. Here, we applied a more general discrete quasi-linear viscoelastic (DQLV) model to identify the static and dynamic time- and frequency-dependent behavior of rabbit medial collateral ligaments.