Basement membrane properties and their recapitulation in organ-on-chip applications

Salimbeigi, Golestan; Vrana, Nihal Engin; Ghaemmaghami, Amir M.; Huri, Pınar Yılgör; McGuinness, Garrett B.

doi:10.1016/j.mtbio.2022.100301

Cited by 23 publications

(28 citation statements)

References 238 publications

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“…The simulation results replicated the trend in the experiments by which greater concentrations of dextrans are observed in the viable epidermis than in the dermis. This points to the role that the basement membrane has as a barrier for diffusion into the dermis [30]. The use of independently derived values for the diffusion and partition coefficients (not calibrated from our experiments) resulted in a model with an adequate prediction capability.…”

Section: Modelling Transdermal Permeation At Atmospheric Pressure: Ba...mentioning

confidence: 83%

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

et al. 2022

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Objectives To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method. Methods Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure. Results Mechanical simulations resulted in skin stretching and thinning (20%–26% hair follicle diameter increase, and 21%–27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 μg $$\bullet$$ ∙ cm−2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 μg $$\bullet$$ ∙ cm−2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from $$\sim$$ ∼ 10 μm2$$\bullet$$ ∙ s−1 to between 200–500 μm2$$\bullet$$ ∙ s−1. Conclusions Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation.

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Section: Modelling Transdermal Permeation At Atmospheric Pressure: Ba...mentioning

confidence: 83%

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

et al. 2022

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“…At present, our model features hepatocytes and endothelial cells but may be improved by adding important resident cells of the sinusoids such as Kupffer cells and hepatic stellate cells. Furthermore, in this work, we used Transwell -like inserts hosting PET membranes that are a common component of OoC devices, as reported by Salimbeigi et al., 2022 . These membranes are standardized but do not fully replicate the Space of Disse basement membrane nano-fibrillar architecture and are characterized by lack of biochemical cues and higher stiffness and thickness (30 μm in comparison to 1.4 μm) if compared to Space of Disse .…”

Section: Discussionmentioning

confidence: 99%

Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer’s Disease Drug

Fanizza

Boeri

Donnaloja

et al. 2023

ACS Biomater. Sci. Eng.

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Liver-related drug metabolism is a key aspect of pharmacokinetics and possible toxicity. From this perspective, the availability of advanced in vitro models for drug testing is still an open need, also to the end of reducing the burden of in vivo experiments. In this scenario, organ-on-a-chip is gaining attention as it couples a state-of-the art in vitro approach to the recapitulation of key in vivo physiological features such as fluidodynamics and a tri-dimensional cytoarchitecture. We implemented a novel liver-on-a-chip (LoC) device based on an innovative dynamic device (MINERVA 2.0) where functional hepatocytes (iHep) have been encapsulated into a 3D hydrogel matrix interfaced through a porous membrane with endothelial cells (iEndo)]. Both lines were derived from human-induced pluripotent stem cells (iPSCs), and the LoC was functionally assessed with donepezil, a drug approved for Alzheimer’s disease therapy. The presence of iEndo and a 3D microenvironment enhanced the expression of liver-specific physiologic functions as in iHep, after 7 day perfusion, we noticed an increase of albumin, urea production, and cytochrome CYP3A4 expression compared to the iHep static culture. In particular, for donepezil kinetics, a computational fluid dynamic study conducted to assess the amount of donepezil diffused into the LoC indicated that the molecule should be able to pass through the iEndo and reach the target iHep construct. Then, we performed experiments of donepezil kinetics that confirmed the numerical simulations. Overall, our iPSC-based LoC reproduced the in vivo physiological microenvironment of the liver and was suitable for potential hepatotoxic screening studies.

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“…32,80 Taking advantage of additional fabrication methods such as bioprinting and electrospinning allows for nanofibers to be considered which structurally resemble the fibrous nature of the membrane proteins in vivo. 81,82 Microfluidic BBB models as well as organon-chip models generally will benefit from future standardization of the materials used to construct the basement membrane.…”

Section: Basement Membrane Proteinsmentioning

confidence: 99%

“…These efforts are also focused on developing alternatives to collagen I and PDL, proteins that are used because they support brain cell growth and differentiation but are not native to the brain. Materials that have been considered for use include hyaluronic acid in combination with a peptide amphiphile that forms β-sheet fibrils along with a proteolytic domain (GPQGIWGQ octapeptide) that is sensitive to matrix metalloproteinase-1 (MMP-1). , Taking advantage of additional fabrication methods such as bioprinting and electrospinning allows for nanofibers to be considered which structurally resemble the fibrous nature of the membrane proteins in vivo. , Microfluidic BBB models as well as organ-on-chip models generally will benefit from future standardization of the materials used to construct the basement membrane.…”

Section: Evaluation Of Bbb Modelsmentioning

confidence: 99%

Applications and Considerations for Microfluidic Systems To Model the Blood–Brain Barrier

Floryanzia,

Nance

2023

ACS Appl. Bio Mater.

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In a myriad of developmental and degenerative brain diseases, characteristic pathological biomarkers are often associated with cerebral blood flow and vasculature. However, the relationship between vascular dysfunction and markers of brain disease is not well-defined. Additionally, it is difficult to deliver effective therapeutics to the brain due to the highly regulated blood–brain barrier (BBB) at the microvasculature interface of the brain. This Review first covers the need for modeling the BBB and the challenges of modeling the BBB. In vitro models of the BBB enable the study of the relationship between vascular dysfunction, BBB function, and disease progression and can serve as a platform to screen therapeutics. In particular, microfluidic-based in vitro BBB models are useful for studying brain vasculature as they support cell culture within the presence of continuous perfusion, which mirrors the in vivo flow and associated stress conditions in the brain. Early microfluidic models of the BBB created the most simplistic models possible that still displayed some functional aspects of the in vivo BBB. Therefore, this Review also discusses the emerging unique ways in which microfluidics in tandem with recent advancements in cell culture, biomaterials, and in vitro modeling can be used to develop more complex and physiologically relevant models of the BBB. Finally, we discuss the current and future state-of-the-art application of microfluidic BBB models for drug development and disease modeling, and the ongoing areas of needed innovation in this field.

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Basement membrane properties and their recapitulation in organ-on-chip applications

Cited by 23 publications

References 238 publications

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device

Development of an Induced Pluripotent Stem Cell-Based Liver-on-a-Chip Assessed with an Alzheimer’s Disease Drug

Applications and Considerations for Microfluidic Systems To Model the Blood–Brain Barrier

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