Microfluidic lumen-based systems for advancing tubular organ modeling

Virumbrales-Muñoz, María; Ayuso, Jesús Manso; Gong, Ming; Humayun, Mouhita; Livingston, Megan; Lugo-Cintrón, Karina M; McMinn, Patrick H.; Álvarez-García, Yasmín R.; Beebe, David J.

doi:10.1039/d0cs00705f

Cited by 60 publications

(43 citation statements)

References 217 publications

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“… 42 Notable examples are blood and lymphatic vessel BMOMs, which have been of increasing interest in the last decade. 43,44 Generally based on lining one or several surfaces (e.g., biocompatible materials or hydrogels) with cells of endothelial lineage (e.g., Human Umbilical Vessel Endothelial Cells or Human Lymphatic Endothelial Cells), these systems also include mechanical cues and supporting cell types 43,45,46 The applications for these BMOMs have ranged from basic cancer biology studies to more applied drug mechanism and drug testing studies. 47–50 More recently, tissue-specific blood vessel and lymphatic vessel BMOMs have filled an existing literature gap exploring the influence of vessel variability (e.g., lymphatic, arteries, capillaries) and tissue specificity in cancer progression, metastasis, and treatment.…”

Section: Advantages Of Bioengineered Microfluidic Organotypic Models mentioning

confidence: 99%

“…In recent years, we have witnessed a handful of studies developing patient-specific organotypic models for drug-testing applications. 43,60–63 Although most of these studies remain at the proof of concept stage and have yet to demonstrate clinical relevance, they help to pave a path forward in how these tools can be further refined to be used clinically.…”

Section: Advantages Of Bioengineered Microfluidic Organotypic Models mentioning

confidence: 99%

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Toward improved in vitro models of human cancer

et al. 2021

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Cancer is a leading cause of death across the world and continues to increase in incidence. Despite years of research, multiple tumors (e.g., glioblastoma, pancreatic cancer) still have limited treatment options in the clinic. Additionally, the attrition rate and cost of drug development have continued to increase. This trend is partly explained by the poor predictive power of traditional in vitro tools and animal models. Moreover, multiple studies have highlighted that cell culture in traditional Petri dishes commonly fail to predict drug sensitivity. Conversely, animal models present differences in tumor biology compared with human pathologies, explaining why promising therapies tested in animal models often fail when tested in humans. The surging complexity of patient management with the advent of cancer vaccines, immunotherapy, and precision medicine demands more robust and patient-specific tools to better inform our understanding and treatment of human cancer. Advances in stem cell biology, microfluidics, and cell culture have led to the development of sophisticated bioengineered microscale organotypic models (BMOMs) that could fill this gap. In this Perspective, we discuss the advantages and limitations of patient-specific BMOMs to improve our understanding of cancer and how these tools can help to confer insight into predicting patient response to therapy.

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Section: Advantages Of Bioengineered Microfluidic Organotypic Models mentioning

confidence: 99%

Section: Advantages Of Bioengineered Microfluidic Organotypic Models mentioning

confidence: 99%

Toward improved in vitro models of human cancer

et al. 2021

Self Cite

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“…The techniques employed in traditional microfabrication are normally limited to rectangular geometries, causing cells to be grown in flat 2D monolayers. To more accurately replicate the lungs from a structural and architectural perspective, microfluidic systems incorporating hydrogels have been shown to enable the creation of perfusable lumen structures [ 27 , 52 ]. Replicating the geometry of the airway lumen and blood vessel is important, as cells grown in lumen shaped monolayers are a more physiological representation and replicate in vivo phenotypes [ 53 ].…”

Section: Modeling Lung Biology On-chipmentioning

confidence: 99%

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

Bennet

Randhawa

Hua

et al. 2021

Cells

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The lungs are affected by illnesses including asthma, chronic obstructive pulmonary disease, and infections such as influenza and SARS-CoV-2. Physiologically relevant models for respiratory conditions will be essential for new drug development. The composition and structure of the lung extracellular matrix (ECM) plays a major role in the function of the lung tissue and cells. Lung-on-chip models have been developed to address some of the limitations of current two-dimensional in vitro models. In this review, we describe various ECM substitutes utilized for modeling the respiratory system. We explore the application of lung-on-chip models to the study of cigarette smoke and electronic cigarette vapor. We discuss the challenges and opportunities related to model characterization with an emphasis on in situ characterization methods, both established and emerging. We discuss how further advancements in the field, through the incorporation of interstitial cells and ECM, have the potential to provide an effective tool for interrogating lung biology and disease, especially the mechanisms that involve the interstitial elements.

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“…The collapsible, stretchable, and perfusable nature of the tubular structures promises crucial mechanosensory cues and other important microphysiological features of intact tissues to be recapitulated within the ECM wall itself, without requiring synthetic elastomeric membranes as support structures, [ 4 ] promising broad applications in lumen‐based organ‐on‐a‐chip platforms. [ 36 ] Examples may include microphysiological models of acute respiratory distress syndrome and ventilator‐induced lung injury. The capacity to alter the cellular composition in the axial direction may prove useful in establishing multi‐organ models along the same ECM‐based tubular structure.…”

Section: Figurementioning

confidence: 99%

One‐Step Formation of Protein‐Based Tubular Structures for Functional Devices and Tissues

Gao

Vaezzadeh

Chow

et al. 2021

Adv Healthcare Materials

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Tubular biological structures consisting of extracellular matrix (ECM) proteins and cells are basic functional units of all organs in animals and humans. ECM protein solutions at low concentrations (5-10 milligrams per milliliter) are abundantly used in 3D cell culture. However, their poor "printability" and minute-long gelation time have made the direct extrusion of tubular structures in bioprinting applications challenging. Here, this limitation is overcome and the continuous, template-free conversion of low-concentration collagen, elastin, and fibrinogen solutions into tubular structures of tailored size and radial, circumferential and axial organization is demonstrated. The approach is enabled by a microfabricated printhead for the consistent circumferential distribution of ECM protein solutions and lends itself to scalable manufacture. The attached confinement accommodates minute-long residence times for pH, temperature, light, ionic and enzymatic gelation. Chip hosted ECM tubular structures are amenable to perfusion with aqueous solutions and air, and cyclic stretching. Predictive collapse and reopening in a crossed-tube configuration promote all-ECM valves and pumps. Tissue level function is demonstrated by factors secreted from cells embedded within the tube wall, as well as endothelial or epithelial barriers lining the lumen. The described approaches are anticipated to find applications in ECM-based organ-on-chip and biohybrid structures, hydraulic actuators, and soft machines.

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Microfluidic lumen-based systems for advancing tubular organ modeling

Abstract: Microfluidic lumen-based systems are microscale models that recapitulate the anatomy and physiology of tubular organs. Here, we review recent microfluidic lumen-based systems and their applications in basic and translational biomedical research.

Cited by 60 publications

References 217 publications

Toward improved in vitro models of human cancer

Toward improved in vitro models of human cancer

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

One‐Step Formation of Protein‐Based Tubular Structures for Functional Devices and Tissues

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