Microfluidic post method for 3-dimensional modeling of platelet–leukocyte interactions

Adv Healthcare Materials

Jiang

et al. 2023

Self Cite

The mechanical stimuli generated by body exercise can be transmitted from cortical bone into the deep bone marrow (mechanopropagation). Excitingly, a mechanosensitive perivascular stem cell niche is recently identified within the bone marrow for osteogenesis and lymphopoiesis. Although it is long known that they are maintained by exercise‐induced mechanical stimulation, the mechanopropagation from compact bone to deep bone marrow vasculature remains elusive of this fundamental mechanobiology field. No experimental system is available yet to directly understand such exercise‐induced mechanopropagation at the bone‐vessel interface. To this end, taking advantage of the revolutionary in vivo 3D deep bone imaging, an integrated computational biomechanics framework to quantitatively evaluate the mechanopropagation capabilities for bone marrow arterioles, arteries, and sinusoids is devised. As a highlight, the 3D geometries of blood vessels are smoothly reconstructed in the presence of vessel wall thickness and intravascular pulse pressure. By implementing the 5‐parameter Mooney–Rivlin model that simulates the hyperelastic vessel properties, finite element analysis to thoroughly investigate the mechanical effects of exercise‐induced intravascular vibratory stretching on bone marrow vasculature is performed. In addition, the blood pressure and cortical bone bending effects on vascular mechanoproperties are examined. For the first time, movement‐induced mechanopropagation from the hard cortical bone to the soft vasculature in the bone marrow is numerically simulated. It is concluded that arterioles and arteries are much more efficient in propagating mechanical force than sinusoids due to their stiffness. In the future, this in‐silico approach can be combined with other clinical imaging modalities for subject/patient‐specific vascular reconstruction and biomechanical analysis, providing large‐scale phenotypic data for personalized mechanobiology discovery.

Section: Discussionmentioning

confidence: 99%

A Novel Computational Biomechanics Framework to Model Vascular Mechanopropagation in Deep Bone Marrow

Adv Healthcare Materials

Jiang

et al. 2023

Self Cite

“…Using a standard soft lithography and single-mask microfabrication process, [17] we created parallel microfluidic channels to model venous capillary anatomies within a few hundred microns on a PDMS chip (Figure 1B). To enable SMAC co-culture of endothelial cells and multiple tumor spheroids, we trialed multiple microchannel dimensions ranging from 300 × 100μm to 1000 × 500μm (cross setion: width × height), and then optimized the design by checking the stability and reproducibility of tumor spheroids culture in the endothelialized channel after perfusion at bulk shear stress τ 0 = 1 to 15 dyn/cm 2 .…”

Section: Resultsmentioning

confidence: 99%

“…After being designed in AutoCAD@ software (version 2015; AutoDesk, San Rafael, CA, USA), the microchannel master was fabricated using dry photoresists. [17a] Firstly, a 6-inch silicon wafer was cleaned and baked for 10 minutes at 200°C, followed by hexamethyldisilazane vapor priming for 30 seconds at 120°C. A layer of 200-μm constant height dry photoresist film (DJ micro laminate SUEX®) was then laminated on the silicon wafer at 65°C.…”

Section: Methodsmentioning

confidence: 99%

“…The CFD simulation was performed over a virtual microfluidic channel (length x 0 =1000 μm, width y 0 = 600 μm, and height z 0 = 300 μm) utilizing ANSYS®Fluent 2020 R1 software (version 20.1; Canonsburg, PA, USA) as previously described. [21, 32] The tumors were reconstructed from the 3D confocal scan using Imaris software (Bitplane) [17a] and placed in the middle of the channel. The tumor and the channel were then meshed into 1 μm grids for an iterative solving process.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

3D spheroid-microvasculature-on-a-chip for tumor-endothelium mechanobiology interplay

Jiang

et al. 2022

Preprint

Self Cite

In the final step of cancer metastasis, tumor cells become lodged in a distant capillary bed, where they can undergo extravasation and form a secondary tumor. While increasing evidence suggests blood/lymphatic flow and shear stress play a critical role in the tumor extravasation process, there is a lack of systematic and biomechanical approaches to recapitulate sophisticated 3D microtissue interactions within the controllable hydrodynamic microenvironment. Here, we report a simple-to-use 3D spheroid-microvasculature-on-a-chip (SMAC) model. Under static and controlled flow conditions, the SMAC recapitulates the biomechanical crosstalk between heterogeneous tumor spheroids and the endothelium in a high-throughput and quantitative manners. As an in vitro metastasis mechanobiology model, we discover 3D spheroid-induced endothelial compression and cell-cell junction degradation in the process of tumor migration and expansion. Lastly, we examine the shear stress effects on the endothelial orientation, polarization as well as the tumor spheroid expansion. Taken together, our SMAC model offers a miniaturized, cost-efficient and versatile platform for future investigation on metastasis mechanobiology, enhanced permeability and retention effect and even personalized therapeutic evaluation.

“…[21][22][23] Blood coagulation tests and platelet function analyses have been undertaken to predict thrombotic risk without vessel wall. [3,24,25] However, such methodologies are reliant on labor-intensive testing, bulky and costly equipment, and specialist interpretation [14,26] -all of which are poorly available in regional and rural health settings. Currently, there is no personalized and affordable point-of-care testing available that allows for tailored risk stratification as well as long-term monitoring.…”

mentioning

confidence: 99%

Novel Movable Typing for Personalized Vein‐Chips in Large Scale: Recapitulate Patient‐Specific Virchow's Triad and its Contribution to Cerebral Venous Sinus Thrombosis

Wang

et al. 2023

Adv Funct Materials

Self Cite

The Vein‐Chip recapitulates CVST Virchow's triad and enables systematic characterization of venous thrombogenesis with respect to fibrin formation and platelet aggregation. Distinct from the arterial setting, platelets universally adhere across the entire CVS Vein‐Chip independent of stenotic geometry and flow disturbance. Intriguingly, fibrin propagates along with the flow direction, but exclusively deposits to the inner vessel wall. Upon inflammatory endothelial injury, fibrin deposition mirrors to the outer vessel wall, but still not in the lumen. Together, the Vein‐Chip promises future applications for personalized thrombotic assessment and monitoring.