Combinatorial in Vitro and in Silico Approach To Describe Shear-Force Dependent Uptake of Nanoparticles in Microfluidic Vascular Models

Charwat, Verena; Calvo, Isabel Olmos; Rothbauer, Mario; Kratz, Sebastian Rudi Adam; Jungreuthmayer, Christian; Zanghellini, Jürgen; Grillari, Johannes; Ertl, Peter

doi:10.1021/acs.analchem.7b04788

Cited by 19 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NPs uptake was dose-dependent parallel to the increase of the flow stimulation up to a critical value (2.25 µL min −1 or 4 dyn cm −2 ). At a higher mechanical load, NPs absorption decreased with inverse relation between concentration and force [190].…”

Section: Absorptionmentioning

confidence: 96%

Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

View full text Add to dashboard Cite

Integration of biophysical stimulation in test systems is established in diverse branches of biomedical sciences including toxicology. This is largely motivated by the need to create novel experimental setups capable of reproducing more closely in vivo physiological conditions. Indeed, we face the need to increase predictive power and experimental output, albeit reducing the use of animals in toxicity testing. In vivo, mechanical stimulation is essential for cellular homeostasis. In vitro, diverse strategies can be used to model this crucial component. The compliance of the extracellular matrix can be tuned by modifying the stiffness or through the deformation of substrates hosting the cells via static or dynamic strain. Moreover, cells can be cultivated under shear stress deriving from the movement of the extracellular fluids. In turn, introduction of physical cues in the cell culture environment modulates differentiation, functional properties, and metabolic competence, thus influencing cellular capability to cope with toxic insults. This review summarizes the state of the art of integration of biophysical stimuli in model systems for toxicity testing, discusses future challenges, and provides perspectives for the further advancement of in vitro cytotoxicity studies.

show abstract

Section: Absorptionmentioning

confidence: 96%

Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

View full text Add to dashboard Cite

show abstract

“…For example, it has been shown that shear stress influences nanoparticle uptake of endothelial cells where higher flow rates led to reduced uptake. Using an in vitro as well as in silico approach, Charwat et al (2018) found that clathrin-mediated uptake of nanoparticles is drastically reduced when exceeding shear forces of 1.8 dyn/cm 2 , implying an important role of shear stress when investigating in vitro nanoparticle uptake. Another study, published by Griep et al (2013) , successfully recreated the smallest unit of the blood brain barrier using immortalized brain endothelial cells to study barrier integrity in the presence of physiological shear force.…”

Section: Microfluidic Mechanobiology In Monolayers and Barrier Modelsmentioning

confidence: 99%

Small Force, Big Impact: Next Generation Organ-on-a-Chip Systems Incorporating Biomechanical Cues

et al. 2018

Self Cite

View full text Add to dashboard Cite

Mechanobiology-on-a-chip is a growing field focusing on how mechanical inputs modulate physico-chemical output in microphysiological systems. It is well known that biomechanical cues trigger a variety of molecular events and adjustment of mechanical forces is therefore essential for mimicking in vivo physiologies in organ-on-a-chip technology. Biomechanical inputs in organ-on-a-chip systems can range from variations in extracellular matrix type and stiffness and applied shear stresses to active stretch/strain or compression forces using integrated flexible membranes. The main advantages of these organ-on-a-chip systems are therefore (a) the control over spatiotemporal organization of in vivo-like tissue architectures, (b) the ability to precisely control the amount, duration and intensity of the biomechanical stimuli, and (c) the capability of monitoring in real time the effects of applied mechanical forces on cell, tissue and organ functions. Consequently, over the last decade a variety of microfluidic devices have been introduced to recreate physiological microenvironments that also account for the influence of physical forces on biological functions. In this review we present recent advances in mechanobiological lab-on-a-chip systems and report on lessons learned from these current mechanobiological models. Additionally, future developments needed to engineer next-generation physiological and pathological organ-on-a-chip models are discussed.

show abstract

“…Among these, self-assembled and autologously formed vascular networks in hydrogel-laden microfluidic channels have proven ideal for studying fundamental biological processes, diseases, and exposure to drugs or toxic compounds. 16,23,24 The success of vasculature-onchip systems is inherently linked to the unique capability to adjust physiological flow conditions, 15 shear forces, 25 nutrient gradients, 14 and biomechanical cues. 11,26 Additionally, the characteristic design flexibility of microfluidic technology has led to the generation of a variety of customized cultivation chamber geometries capable of precisely controlling cellcell, cell-matrix, and cell-molecule interactions.…”

Section: Introductionmentioning

confidence: 99%

“…28 As an example, mechanobiological stimulation via directional interstitial fluid flow increases tumor cell entry into lymphatic capillaries and stimulates lymphatic sprouting. 29,18 Emulating the mechanobiological environment regarding matrix elasticity, 30 fluid flow, 31 or nutrient gradients [32][33][34] is crucial for developing reliable and accurate in vitro systems. We have previously shown that mechanobiological control over shear stress and growth factor gradients allows manipulation of vascular network formation and nanoparticle uptake by endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

Bachmann¹,

Spitz²,

Jordan³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulation's importance on lymphatic sprout formation. Our microvascular model's key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

show abstract

Combinatorial in Vitro and in Silico Approach To Describe Shear-Force Dependent Uptake of Nanoparticles in Microfluidic Vascular Models

Cited by 19 publications

References 38 publications

Integrating Biophysics in Toxicology

Integrating Biophysics in Toxicology

Small Force, Big Impact: Next Generation Organ-on-a-Chip Systems Incorporating Biomechanical Cues

Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

Contact Info

Product

Resources

About