Alveolar mimics with periodic strain and its effect on the cell layer formation

Radiom, Milad; He, Yuqing; Peng‐Wang, Juan; Baeza‐Squiban, Armelle; Berret, Jean‐François; Chen, Yong

doi:10.1002/bit.27458

Cited by 22 publications

(40 citation statements)

References 61 publications

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“…Using a similar platform, the same group further examined the influence of mechanical strain on alveolar epithelial wound healing [ 65 ]. Furthermore, instead of using conventional PDMS membrane, the same group developed a model of alveolar air–tissue interface on a chip consisting of an array of suspended hexagonal monolayers of nanofibers (made from gelatin or collagen + elastin) supported by microframes [ 66 , 67 ]. The membrane was integrated into a microfluidic device for the patch integration.…”

Section: Lung-on-a-chipmentioning

confidence: 99%

Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

et al. 2021

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Organ-on-a-chip (OOC) uses the microfluidic 3D cell culture principle to reproduce organ- or tissue-level functionality at a small scale instead of replicating the entire human organ. This provides an alternative to animal models for drug development and environmental toxicology screening. In addition to the biomimetic 3D microarchitecture and cell–cell interactions, it has been demonstrated that mechanical stimuli such as shear stress and mechanical strain significantly influence cell behavior and their response to pharmaceuticals. Microfluidics is capable of precisely manipulating the fluid of a microenvironment within a 3D cell culture platform. As a result, many OOC prototypes leverage microfluidic technology to reproduce the mechanically dynamic microenvironment on-chip and achieve enhanced in vitro functional organ models. Unlike shear stress that can be readily generated and precisely controlled using commercial pumping systems, dynamic systems for generating proper levels of mechanical strains are more complicated, and often require miniaturization and specialized designs. As such, this review proposes to summarize innovative microfluidic OOC platforms utilizing mechanical actuators that induce deflection of cultured cells/tissues for replicating the dynamic microenvironment of human organs.

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Section: Lung-on-a-chipmentioning

confidence: 99%

Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

et al. 2021

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“…More recent studies have shown that membranes made of electrospun nanofibers or ECM hydrogels have a better biocompatibility and an improved mechanic property with respect to plastic or elastomeric membranes. [ 27–30 ] Yet, these membranes were not thin enough or made of synthetic polymers. Knowing that the natural BM made of type IV collagen and laminin is dense thin (≈100 nm thick), uniform, and highly permeable, it is important to recapitulate these essential features.…”

Section: Introductionmentioning

confidence: 99%

Generation of Alveolar Epithelium Using Reconstituted Basement Membrane and hiPSC‐Derived Organoids

Rofaani

Huang

et al. 2022

Adv Healthcare Materials

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In vitro modeling of alveolar epithelium needs to recapitulate features of both cellular and noncellular components of the lung tissues. Herein, a method is presented to generate alveolar epithelium by using human induced pluripotent stem cells (hiPSCs) and reconstituted or artificial basement membrane (ABM). The ABM is obtained by self‐assembling type IV collagen and laminin with a monolayer of crosslinked gelatin nanofibers as backbone and a patterned honeycomb microframe for handling. Alveolar organoids are obtained from hiPSCs and then dissociated into single cells. After replating the alveolar cells on the ABM and a short‐period incubation under submerged and air–liquid interface culture conditions, an alveolar epithelium is achieved, showing high‐level expressions of both alveolar cell‐specific proteins and characteristic tight junctions. Besides, endothelial cells derived from the same hiPSCs are cocultured on the backside of the epithelium, forming an air–blood barrier. The method is generic and can potentially be applied to other types of artificial epithelium and endothelium.

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“…24 This approach offers the further benefit that properties such as fiber diameter, fiber orientation, porosity, mechanical strength, stretchability and thickness can be tailored to mimic the properties of the native ECM. 25 Electrospun membranes with fiber diameters in the micrometer range have previously been used to mimic the alveolar capillary basement membrane in macro-and microscale devices 11, 26, 27 However, only a few of these devices have incorporated basolateral media flow and these have been limited to macroscale devices. 28 Such macroscale devices are costly and take up considerable space, and are therefore limited with regard to how many replicates can be run in parallel.…”

Section: Introductionmentioning

confidence: 99%

“…Several different in vitro lung tissue models with cyclic mechanical stretch have been developed by integrating manufacturing techniques with cell culture. [5][6][7][8][9][10][11][12][13][14] Currently utilized models span from macro to microscale devices, the latter of which allow for complex devices to be manufactured with similar dimensions to the natural cell microenvironment. These devices have been used to study alveolar barrier function, 10,11,15 lung disease 13,16 , lung injury 7,14 and drug response 16,17 using lung on a chip devices.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9][10][11][12][13][14] Currently utilized models span from macro to microscale devices, the latter of which allow for complex devices to be manufactured with similar dimensions to the natural cell microenvironment. These devices have been used to study alveolar barrier function, 10,11,15 lung disease 13,16 , lung injury 7,14 and drug response 16,17 using lung on a chip devices. However, the study of pathological mechanical stretch on biologically relevant membranes has thus far been challenging in these setups due to the use of 2D planar membranes which do not mimic the nanofibrous basement membrane of the alveolus that can also undergo cyclic mechanical stretch within the ranges known to be present in VILI.…”

Section: Introductionmentioning

confidence: 99%

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3D printed lung on a chip device with a stretchable nanofibrous membrane for modeling ventilator induced lung injury

Taş

Rehnberg

et al. 2021

Preprint

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Mechanical ventilation is often required in patients with pulmonary disease to maintain adequate gas exchange. Despite improved knowledge regarding the risks of over ventilating the lung, ventilator induced lung injury (VILI) remains a major clinical problem due to inhomogeneities within the diseased lung itself as well as the need to increase pressure or volume of oxygen to the lung as a life-saving measure. VILI is characterized by increased physical forces exerted within the lung, which results in cell death, inflammation and long-term fibrotic remodeling. Animal models can be used to study VILI, but it is challenging to distinguish the contributions of individual cell types in such a setup. In vitro models, which allow for controlled stretching of specific lung cell types have emerged as a potential option, but these models and the membranes used in them are unable to recapitulate some key features of the lung such as the 3D nanofibrous structure of the alveolar basement membrane while also allowing for cells to be cultured at an air liquid interface (ALI) and undergo increased mechanical stretch that mimics VILI. Here we develop a lung on a chip device with a nanofibrous synthetic membrane to provide ALI conditions and controllable stretching, including injurious stretching mimicking VILI. The lung on a chip device consists of a thin (i.e. ~20 μm) stretchable poly(caprolactone) (PCL) nanofibrous membrane placed between two channels fabricated in polydimethylsiloxane (PDMS) using 3D printed molds. We demonstrate that this lung on a chip device can be used to induce mechanotrauma in lung epithelial cells due to cyclic pathophysiologic stretch (~25%) that mimics clinical VILI. Pathophysiologic stretch induces cell injury and subsequently cell death, which results in loss of the epithelial monolayer, a feature mimicking the early stages of VILI. We also validate the potential of our lung on a chip device to be used to explore cellular pathways known to be altered with mechanical stretch and show that pathophysiologic stretch of lung epithelial cells causes nuclear translocation of the mechanotransducers YAP/TAZ. In conclusion, we show that a breathable lung on a chip device with a nanofibrous membrane can be easily fabricated using 3D printing of the lung on a chip molds and that this model can be used to explore pathomechanisms in mechanically induced lung injury.

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Alveolar mimics with periodic strain and its effect on the cell layer formation

Cited by 22 publications

References 61 publications

Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Mechanical Strain-Enabled Reconstitution of Dynamic Environment in Organ-on-a-Chip Platforms: A Review

Generation of Alveolar Epithelium Using Reconstituted Basement Membrane and hiPSC‐Derived Organoids

3D printed lung on a chip device with a stretchable nanofibrous membrane for modeling ventilator induced lung injury

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