Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function

Sriram, Gopu; Alberti, Massimo; Dancik, Yuri; Wu, Bo; Wu, Ruige; Feng, Z.; Ramasamy, Srinivas; Bigliardi, Paul L.; Bigliardi-Qi, Mei; Wang, Zhiping

doi:10.1016/j.mattod.2017.11.002

Cited by 202 publications

(211 citation statements)

References 70 publications

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“…Moreover, as most of the current 2D and 3D skin wound infection models are static in vitro models [107,189], the dynamic interactions between bacteria and host cells during the wound-healing process remains unclear. With the advancement of novel biomaterials and microfluidic systems [190][191][192][193], new approaches, such as 3D bioprinting technology, can potentially be applied to fabricate skin-on-a-chip systems with an ECM embedded and spatial heterogeneity incorporated. This may further facilitate the development of more representative microfluidic skin disease models in the future [194].…”

Section: Skin-on-a-chipmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

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Section: Skin-on-a-chipmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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“…Therefore, from the perspective of developmental biology, the influence of fluid flow‐induced shear stress on the biochemical and molecular aspects of the keratinocytes is an important issue. in vitro studies pertaining to the development of artificial skin in perfusion bioreactor further confirm the influence of flow‐induced shear on the physiology of skin keratinocytes either upon direct or indirect flow exposure (Kalyanaraman, Supp, & Boyce, ; Ramadan & Ting, ; Sriram et al, ; Strüver, Friess, & Hedtrich, ). As per these studies, the application of fluid‐induced shear stress could enhance the maturation of the epidermis and modulate its barrier function (Sriram et al, ).…”

Section: Introductionmentioning

confidence: 84%

“…in vitro studies pertaining to the development of artificial skin in perfusion bioreactor further confirm the influence of flow‐induced shear on the physiology of skin keratinocytes either upon direct or indirect flow exposure (Kalyanaraman, Supp, & Boyce, ; Ramadan & Ting, ; Sriram et al, ; Strüver, Friess, & Hedtrich, ). As per these studies, the application of fluid‐induced shear stress could enhance the maturation of the epidermis and modulate its barrier function (Sriram et al, ). In recent years, researches have demonstrated that other mechanical stimuli like uniaxial/biaxial stretching (Kippenberger et al, ), matrix stiffness (Gupta et al, ; Kenny et al, ; Zarkoob, Bodduluri, Ponnaluri, Selby, & Sander, ), and cyclic strain (Takei et al, ; ) could influence the physiological aspects of the keratinocytes, thereby proving their mechanoresponsiveness.…”

Section: Introductionmentioning

confidence: 84%

Keratinocytes are mechanoresponsive to the microflow‐induced shear stress

2019

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Here, we have reported that keratinocytes respond to the microflow‐induced shear stress both at the collective and individual cell level. Using a microfluidic setup, we categorically showed that low shear stress of magnitude 0.06 dyne/cm2 could induce morphological variation and cytoskeletal reorganization in keratinocyte, whereas higher shear stress (6 dyne/cm2) resulted in cellular disruption. Using a series of blocker molecules specific to different mechanotransducers, we demonstrated the pivotal role of actin network in keratinocyte mechanoresponsiveness in conjugation with myosin and lipid rafts. Flow‐induced shear stress also induced significant elevation in E‐cadherin and Zonula occludens‐1 (ZO‐1) expression levels. We further showed that under the influence of shear stress, the extent of colocalization of E‐cadherin and ZO‐1 was more at the cell–cell junction that indicates an improvement in the epithelial phenotype. An increase in the expression of nuclear lamin was also observed in the sheared cells that suggest the transmission of mechanical signals to the nucleus. It is envisioned that this study may find its application in basic and applied organogenesis of the epidermis.

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“…In the “skin‐on‐chip” technology, different cells are cultured in a microscale environment using a microfluidic culture device . The “skin‐on‐chip” model offers dynamic perfusion and controlled ventilation which seems to result in beneficial effects in terms of epidermal morphogenesis, differentiation and barrier function . Microfluidic devices also allow the study of the migration of immune cells.…”

Section: D Skin Modelsmentioning

confidence: 92%

Skin microbiota and human 3D skin models

Rademacher

Simanski

Gläser

et al. 2018

Experimental Dermatology

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Although the role of the microbiota in skin homeostasis is still emerging, there is growing evidence that an intact microbiota supports the skin barrier. The increasing number of research efforts that are trying to shed more light on the human skin-microbiota interaction requires the use of suitable experimental models. Three-dimensional (3D) skin equivalents have been established as a valuable tool in dermatological research because they contain a fully differentiated epidermal barrier that reflects the morphological and molecular characteristics of normal human epidermis. In this review, we provide an overview of current 3D skin models and illustrate the potential of 3D skin models to study the human skin-microbiota interplay.

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Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function

Cited by 202 publications

References 70 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Keratinocytes are mechanoresponsive to the microflow‐induced shear stress

Skin microbiota and human 3D skin models

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