Recreating cellular barriers in human microphysiological systems in-vitro

Mancinelli, E; Takuma, Megumi; Fujie, Toshinori; Pensabene, V

doi:10.1109/embc48229.2022.9870981

Cited by 3 publications

(4 citation statements)

References 23 publications

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“…Previous studies have shown the biocompatibility of ultrathin polymeric films with different cell types, either as plain 68,69 or porous structures. 46,56 It is crucial to confirm that the compatibility of porous PDLLA nanofilms persists when they are confined in a microfluidic setup and that they can facilitate the growth of endothelial cells and the formation of a complete endothelial layer, effectively serving as an artificial BM. Combining the natural adhesive properties of PDLLA nanofilms and oxygen plasma activation of surfaces, we established a secure bond between the nanofilm and the PDMS surface.…”

Section: Combining Roll-to-roll Gravure Coating and Polymer Phase Sep...mentioning

confidence: 99%

“…In our previous study, we examined the compatibility of porous poly(D,L-lactic acid) (PDLLA) nanofilms, fabricated combining R2R gravure coating and polymer phase separation, as substrates for endothelial cell culture, and we have provided a procedure for integrating these into a dual-chamber microfluidic system. 56 In this work, we assessed their off-chip characteristics as an artificial BM replica, including thickness, porosity, permeability, and Young's modulus. Using human umbilical endothelial cells (HUVECs) as a model of endothelial cells, we first showed cell proliferation and barrier formation into an open microfluidic device and Transwell inserts that integrate PDLLA nanofilms.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, coupling with the polymer phase separation process eliminates the need for additional steps required to control vapor exposure in the process of vapor-induced phase separation. In our previous study, we examined the compatibility of porous poly( d , l -lactic acid) (PDLLA) nanofilms, fabricated combining R2R gravure coating and polymer phase separation, as substrates for endothelial cell culture, and we have provided a procedure for integrating these into a dual-chamber microfluidic system . In this work, we assessed their off-chip characteristics as an artificial BM replica, including thickness, porosity, permeability, and Young’s modulus.…”

Section: Introductionmentioning

confidence: 99%

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Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip

Mancinelli,

Zushi,

Takuma

et al. 2024

ACS Appl. Mater. Interfaces

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Organs-on-chips (OoCs) support an organotypic human cell culture in vitro. Precise representation of basement membranes (BMs) is critical for mimicking physiological functions of tissue interfaces. Artificial membranes in polyester (PES) and polycarbonate (PC) commonly used in in vitro models and OoCs do not replicate the characteristics of the natural BMs, such as submicrometric thickness, selective permeability, and elasticity. This study introduces porous poly(D,L-lactic acid) (PDLLA) nanofilms for replicating BMs in in vitro models and demonstrates their integration into microfluidic chips. Using roll-to-roll gravure coating and polymer phase separation, we fabricated transparent ∼200 nm thick PDLLA films. These nanofilms are 60 times thinner and 27 times more elastic than PES membranes and show uniformly distributed pores of controlled diameter (0.4 to 1.6 μm), which favor cell compartmentalization and exchange of large water-soluble molecules. Human umbilical vein endothelial cells (HUVECs) on PDLLA nanofilms stretched across microchannels exhibited 97% viability, enhanced adhesion, and a higher proliferation rate compared to their performance on PES membranes and glass substrates. After 5 days of culture, HUVECs formed a functional barrier on suspended PDLLA nanofilms, confirmed by a more than 10-fold increase in transendothelial electrical resistance and blocked 150 kDa dextran diffusion. When integrated between two microfluidic channels and exposed to physiological shear stress, despite their ultrathin thickness, PDLLA nanofilms upheld their integrity and efficiently maintained separation of the channels. The successful formation of an adherent endothelium and the coculture of HUVECs and human astrocytes on either side of the suspended nanofilm validate it as an artificial BM for OoCs. Its submicrometric thickness guarantees intimate contact, a key feature to mimic the blood−brain barrier and to study paracrine signaling between the two cell types. In summary, porous PDLLA nanofilms hold the potential for improving the accuracy and physiological relevance of the OoC as in vitro models and drug discovery tools.

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Section: Combining Roll-to-roll Gravure Coating and Polymer Phase Sep...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip

Mancinelli,

Zushi,

Takuma

et al. 2024

ACS Appl. Mater. Interfaces

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show abstract

“…The CNS in vertebrates is protected by many cellular barriers that limit and regulate the ability of certain molecules and cells to enter the brain parenchyma [ 11 ]. Three main barriers, the BBB, blood-cerebrospinal fluid barrier, and cerebrospinal fluid-brain barrier, protect neurons from harmful substances transmitted through the bloodstream [ 12 ].…”

Section: Structure Of the Blood‒brain Barrier (Bbb) In Vertebratesmentioning

confidence: 99%

Toxoplasma rhoptry proteins that affect encephalitis outcome

Wang,

Qu,

Chen

et al. 2023

Cell Death Discov.

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Toxoplasma gondii, a widespread obligate intracellular parasite, can infect almost all warm-blooded animals, including humans. The cellular barrier of the central nervous system (CNS) is generally able to protect the brain parenchyma from infectious damage. However, T. gondii typically causes latent brain infections in humans and other vertebrates. Here, we discuss how T. gondii rhoptry proteins (ROPs) affect signaling pathways in host cells and speculate how this might affect the outcome of Toxoplasma encephalitis.

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Towards Novel Biomimetic In Vitro Models of the Blood–Brain Barrier for Drug Permeability Evaluation

Mármol,

Abizanda-Campo,

Ayuso

et al. 2023

Bioengineering

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Current available animal and in vitro cell-based models for studying brain-related pathologies and drug evaluation face several limitations since they are unable to reproduce the unique architecture and physiology of the human blood–brain barrier. Because of that, promising preclinical drug candidates often fail in clinical trials due to their inability to penetrate the blood–brain barrier (BBB). Therefore, novel models that allow us to successfully predict drug permeability through the BBB would accelerate the implementation of much-needed therapies for glioblastoma, Alzheimer’s disease, and further disorders. In line with this, organ-on-chip models of the BBB are an interesting alternative to traditional models. These microfluidic models provide the necessary support to recreate the architecture of the BBB and mimic the fluidic conditions of the cerebral microvasculature. Herein, the most recent advances in organ-on-chip models for the BBB are reviewed, focusing on their potential to provide robust and reliable data regarding drug candidate ability to reach the brain parenchyma. We point out recent achievements and challenges to overcome in order to advance in more biomimetic in vitro experimental models based on OOO technology. The minimum requirements that should be met to be considered biomimetic (cellular types, fluid flow, and tissular architecture), and consequently, a solid alternative to in vitro traditional models or animals.

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Recreating cellular barriers in human microphysiological systems in-vitro

Cited by 3 publications

References 23 publications

Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip

Porous Polymeric Nanofilms for Recreating the Basement Membrane in an Endothelial Barrier-on-Chip

Toxoplasma rhoptry proteins that affect encephalitis outcome

Towards Novel Biomimetic In Vitro Models of the Blood–Brain Barrier for Drug Permeability Evaluation

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