Lysyl Oxidase Production by Murine C3H10T1/2 Mesenchymal Stem Cells Is Increased by TGFßs and Differentially Modulated by Mechanical Stimuli.

Tendons are frequently injured and have limited regenerative capacity. This motivates tissue engineering efforts aimed at restoring tendon function through strategies to direct functional tendon formation. Generation of a crosslinked collagen matrix is paramount to forming mechanically functional tendon. However, it is unknown how lysyl oxidase (LOX), the primary mediator of enzymatic collagen crosslinking, is regulated by stem cells. This study investigates how multiple factors previously identified to promote tendon formation and healing (transforming growth factor [TGF]ß1 and TGFß2, mechanical stimuli, and hypoxia-inducible factor [HIF]-1α) regulate LOX production in the murine C3H10T1/2 mesenchymal stem cell (MSC) line. We hypothesized that TGFß signaling promotes LOX activity in C3H10T1/2 MSCs, which is regulated by both mechanical stimuli and HIF-1α activation. TGFß1 and TGFß2 increased LOX levels as a function of concentration and time. Inhibiting the TGFß type I receptor (TGFßRI) decreased TGFß2-induced LOX production by C3H10T1/2 MSCs. Low (5 mPa) and high (150 mPa) magnitudes of fluid shear stress were applied to test impacts of mechanical stimuli, but without TGFß2, loading alone did not alter LOX levels. Low loading (5 mPa) with TGFß2 increased LOX at 7 days greater than TGFß2 treatment alone. Neither HIF-1α knockdown (siRNA) nor activation (CoCl2) affected LOX levels. Ultimately, results suggest that TGFß2 and appropriate loading magnitudes contribute to LOX production by C3H10T1/2 MSCs. Potential application of these findings includes treatment with TGFß2 and appropriate mechanical stimuli to modulate LOX production by stem cells to ultimately control collagen matrix stiffening and support functional tendon formation.

Application of Dynamic Mode Decomposition to Study Temporal Flow Behavior in a Saccular Aneurysm.

Aneurysms are abnormal expansion of weakened blood vessels which can cause mortality or long-term disability upon rupture. Several studies have shown that inflow conditions spatially and temporally influence aneurysm flow behavior. The objective of this investigation is to identify impact of inflow conditions on spatio-temporal flow behavior in an aneurysm using dynamic mode decomposition (DMD). For this purpose, low-frame rate velocity field measurements are performed in an idealized aneurysm model using particle image velocimetry (PIV). The inflow conditions are precisely controlled using a ViVitro SuperPump system where nondimensional fluid parameters such as peak Reynolds number (Rep) and Womersely number (α) are varied from 50-270 and 2-5, respectively. The results show the ability of DMD to identify the spatial flow structures and their frequency content. Furthermore, DMD captured the impact of inflow conditions, and change in mode shapes, amplitudes, frequency, and growth rate information is observed. The DMD low-order flow reconstruction also showed the complex interplay of flow features for each inflow scenario. Furthermore, the low-order reconstruction results provided a mathematical description of the flow behavior in the aneurysm which captured the vortex formation, evolution, and convection in detail. These results indicated that the vortical structure behavior varied with the change in α while its strength and presence of secondary structures are influenced by the change in Rep.

Application of Proper Orthogonal Decomposition to Study Coherent Flow Structures in a Saccular Aneurysm.

Aneurysms are localized expansions of weakened blood vessels that can be debilitating or fatal upon rupture. Previous studies have shown that flow in an aneurysm exhibits complex flow structures that are correlated with its inflow conditions. Therefore, the objective of this study was to demonstrate the application of proper orthogonal decomposition (POD) to study the impact of different inflow conditions on energetic flow structures and their temporal behavior in an aneurysm. To achieve this objective, experiments were performed on an idealized rigid sidewall aneurysm model. A piston pump system was used for precise inflow control, i.e., peak Reynolds number (Rep) and Womersley number (α) were varied from 50 to 270 and 2 to 5, respectively. The velocity flow field measurements at the midplane location of the idealized aneurysm model were performed using particle image velocimetry (PIV). The results demonstrate the efficacy of POD in decomposing complex data, and POD was able to capture the energetic flow structures unique to each studied inflow condition. Furthermore, the time-varying coefficient results highlighted the interplay between the coefficients and their corresponding POD modes, which in turn helped explain how POD modes impact certain flow features. The low-order reconstruction results were able to capture the flow evolution and provide information on complex flow in an aneurysm. The POD and low-order reconstruction results also indicated that vortex formation, evolution, and convection varied with an increase in α, while vortex strength and formation of secondary structures were correlated with an increase in Rep.