Multiscale reverse engineering of the human ocular surface

Seo, Jeongyun; Byun, Woo Yul; Alisafaei, Farid; Georgescu, Andrei; Yi, Yoon-Suk; Massaro-Giordano, Mina; Shenoy, Vivek B.; Lee, Vivian; Bunya, Vatinee Y.; Huh, Dongeun

doi:10.1038/s41591-019-0531-2

Cited by 113 publications

(88 citation statements)

References 55 publications

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“…innovations have helped mitigate some of the drawbacks of traditional laboratory species-for instance providing manual blinking and supplementary tear flow in anesthetized rabbits, 324 or reverse-engineering the ocular surface using human cells in vitro 325 -however, the authors believe the complexity of the ocular surface and integrated lacrimal functional unit cannot be fully recreated without in vivo conditions in awake subjects.…”

Section: Discussionmentioning

confidence: 99%

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

Sebbag

Mochel

2020

Medicinal Research Reviews

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Preclinical animal studies provide valuable opportunities to better understand human diseases and contribute to major advances in medicine. This review provides a comprehensive overview of ocular parameters in humans and selected animals, with a focus on the ocular surface, detailing species differences in ocular surface anatomy, physiology, tear film dynamics and tear film composition. We describe major pitfalls that tremendously limit the translational potential of traditional laboratory animals (i.e., rabbits, mice, and rats) in ophthalmic research, and highlight the benefits of integrating companion dogs with clinical analogues to human diseases into preclinical pharmacology studies. This One Health approach can help accelerate and improve the framework in which ophthalmic research is translated to the human clinic. Studies can be conducted in canine subjects with naturally occurring or noninvasively induced ocular surface disorders (e.g., dry eye disease, conjunctivitis), reviewed herein, and tear fluid can be easily retrieved from canine eyes for various bioanalytical purposes. In this review, we discuss common tear collection methods, including capillary tubes and Schirmer tear strips, and provide guidelines for tear sampling and extraction to improve the reliability of analyte quantification (drugs, proteins, others).

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Section: Discussionmentioning

confidence: 99%

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

Sebbag

Mochel

2020

Medicinal Research Reviews

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“…Engineers are attempting to mimic these dynamic processes to build more life‐like tissues using microfluidic, 3D bioprinting, and organoid technologies. [ 1–4 ] Organoids, 3D tissues grown from stem cells, are an essential approach because of the remarkable cellular diversity and spatial structure that can be achieved through processes of “self‐organization,” including spontaneous cell sorting and spatially varied cell differentiation. [ 5 ] However, organoids have largely not addressed longer length‐scale (>0.5 mm) tissue developmental processes beyond local self‐organization.…”

Section: Figurementioning

confidence: 99%

Guiding Cell Network Assembly using Shape‐Morphing Hydrogels

et al. 2020

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Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self‐organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape‐morphing materials called “kinomorphs” that rationally control the shape and size of multicellular networks are described. Kinomorphs are sheets of ECM that change their shape, size, and density depending on patterns of cell contractility within them. It is shown that these changes can manipulate structure‐forming behaviors of epithelial cells in many spatial locations at once. Kinomorphs are built using a new photolithographic technology to pattern single cells into ECM sheets that are >10× larger than previously described. These patterns are designed to partially mimic the branch geometry of the embryonic kidney epithelial network. Origami‐inspired simulations are then used to predict changes in kinomorph shapes. Last, kinomorph dynamics are shown to provide a centimeter‐scale program that sets specific spatial locations in which ≈50 µm‐diameter epithelial tubules form by cell coalescence and structural maturation. The kinomorphs may significantly advance organ‐scale tissue construction by extending the spatial range of cell self‐organization in emerging model systems such as organoids.

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“…[ 446,447,449 ] In addition to BRB, the corneal epithelium (cornea‐on‐a‐chip), which experiences blinking‐induced pulsatile forces and cyclic rehydration of lachrymal fluid in an air‐liquid interface, has also been used to investigate the differentiation of corneal epithelial cells, dry eye disease‐induced epithelial stress, and eye drop‐assisted drug permeation, lubrication, and mass transport. [ 451 ] Overall, the intricate and complex ocular niche presents great potential for further improvement of these microfluidic platforms which could eventually assist in high‐content screening of drugs for ocular diseases.…”

Section: Modeling Vascular Mechanopathology In Vascularized Microphysmentioning

confidence: 99%

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

Pradhan

Banda

Farino

et al. 2020

Adv Healthcare Materials

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The vascular system is integral for maintaining organ‐specific functions and homeostasis. Dysregulation in vascular architecture and function can lead to various chronic or acute disorders. Investigation of the role of the vascular system in health and disease has been accelerated through the development of tissue‐engineered constructs and microphysiological on‐chip platforms. These in vitro systems permit studies of biochemical regulation of vascular networks and parenchymal tissue and provide mechanistic insights into the biophysical and hemodynamic forces acting in organ‐specific niches. Detailed understanding of these forces and the mechanotransductory pathways involved is necessary to develop preventative and therapeutic strategies targeting the vascular system. This review describes vascular structure and function, the role of hemodynamic forces in maintaining vascular homeostasis, and measurement approaches for cell and tissue level mechanical properties influencing vascular phenomena. State‐of‐the‐art techniques for fabricating in vitro microvascular systems, with varying degrees of biological and engineering complexity, are summarized. Finally, the role of vascular mechanobiology in organ‐specific niches and pathophysiological states, and efforts to recapitulate these events using in vitro microphysiological systems, are explored. It is hoped that this review will help readers appreciate the important, but understudied, role of vascular‐parenchymal mechanotransduction in health and disease toward developing mechanotherapeutics for treatment strategies.

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Multiscale reverse engineering of the human ocular surface

Cited by 113 publications

References 55 publications

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface

Guiding Cell Network Assembly using Shape‐Morphing Hydrogels

Biofabrication Strategies and Engineered In Vitro Systems for Vascular Mechanobiology

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