Keratinocytes are mechanoresponsive to the microflow‐induced shear stress

Agarwal, Tarun; Narayana, Gautham Hari Narayana Sankara; Banerjee, Indranil

doi:10.1002/cm.21521

Cited by 18 publications

(14 citation statements)

References 54 publications

(96 reference statements)

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“…Agarwall et al showed that epidermal keratinocytes are sensitive to microflow-induced shear stress [ 57 ]. These cells exhibited mechanoresponsive structural reorganization under the influence of shear stresses of magnitude 0.06 dyne/cm 2 and cellular damage under shear stresses of magnitude 6 dyne/cm 2 .…”

Section: Key Requirements For the Development Of Skin-on-a-chip Devicesmentioning

confidence: 99%

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

Zoio

Oliva

2022

Pharmaceutics

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The increased demand for physiologically relevant in vitro human skin models for testing pharmaceutical drugs has led to significant advancements in skin engineering. One of the most promising approaches is the use of in vitro microfluidic systems to generate advanced skin models, commonly known as skin-on-a-chip (SoC) devices. These devices allow the simulation of key mechanical, functional and structural features of the human skin, better mimicking the native microenvironment. Importantly, contrary to conventional cell culture techniques, SoC devices can perfuse the skin tissue, either by the inclusion of perfusable lumens or by the use of microfluidic channels acting as engineered vasculature. Moreover, integrating sensors on the SoC device allows real-time, non-destructive monitoring of skin function and the effect of topically and systemically applied drugs. In this Review, the major challenges and key prerequisites for the creation of physiologically relevant SoC devices for drug testing are considered. Technical (e.g., SoC fabrication and sensor integration) and biological (e.g., cell sourcing and scaffold materials) aspects are discussed. Recent advancements in SoC devices are here presented, and their main achievements and drawbacks are compared and discussed. Finally, this review highlights the current challenges that need to be overcome for the clinical translation of SoC devices.

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Section: Key Requirements For the Development Of Skin-on-a-chip Devicesmentioning

confidence: 99%

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

Zoio

Oliva

2022

Pharmaceutics

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“…[82] These stimuli can modulate cell behavior, inducing morphological changes, proliferation, migration and altering phenotypic expression leading to harmful or therapeutic impacts on skin health. [83,84] Substrate stiffness plays an important role in regulating cell morphology, adhesion, and phenotypic expression. [82] It is common for 3D skin models to include epidermal keratinocytes cultured on either cellular or acellular hydrogels with mechanical properties representative of the dermis.…”

Section: Mechanical Stimulationmentioning

confidence: 99%

Evaluation of in vitro human skin models for studying effects of external stressors and stimuli and developing treatment modalities

Sutterby

Thurgood

Baratchi

et al. 2021

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Skin is exposed to a variety of potential stressors and stimulators that may impact homeostasis, healing, tumor development, inflammation, and irritation. As such it is important to understand the impact that these stimuli have on skin health and function, and to develop therapeutic interventions. Animal experiments have been the gold standard for testing the safety and efficacy of therapeutics and observing disease pathology for centuries. However, complex ethics, costs, time consumption, and interspecies variation limit the transferability of results to humans and reduce their repeatability and reliability. Furthermore, traditional 2D cell studies are not representative of human tissue. Skin tissue is a dynamic environment, and when cells are isolated in unphysiologically stiff, static petri dishes their behavior, and phenotypic expression is altered. Increasingly complex in vitro models of human skin, including organoids, 3D bioprinting, and skin-on-a-chip platforms, present the opportunity to gain insight into how stressors affect tissue at a cellular level in a controlled and repeatable environment. This insight can be leveraged to further understand pathological skin conditions and better formulate and validate drugs and therapeutics. Here, we will discuss the application of in vitro skin modeling to investigating the effects of mechanical, electromagnetic, and chemical stressors on skin. 3D bioprinting, drug development, in vitro, organoid, skin model, skin-on-chip This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…However, epidermis exposure to shear stress during the culture process prior to ventilation has been shown to induce morphological variation, including polarization of columnar basal keratinocytes, cytoskeletal reorganization, improved epithelial phenotype, and thickening of the viable epidermis. [71,80] The magnitude of shear stress exposure on keratinocytes influences cell viability, with low shear stress, 0.06 dyne cm −2 , shown to improve the epidermal model and high shear stress, 6 dyne cm −2 , resulting in cellular disruption. [80] Hence, low shear, double-sided perfusion during cell culturing should be considered necessary to improve skin models.…”

Section: Perfusable Skin Modelsmentioning

confidence: 99%

“…[71,80] The magnitude of shear stress exposure on keratinocytes influences cell viability, with low shear stress, 0.06 dyne cm −2 , shown to improve the epidermal model and high shear stress, 6 dyne cm −2 , resulting in cellular disruption. [80] Hence, low shear, double-sided perfusion during cell culturing should be considered necessary to improve skin models.…”

Section: Perfusable Skin Modelsmentioning

confidence: 99%

Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin

Sutterby

Thurgood

Baratchi

et al. 2020

Small

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The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin‐on‐a‐chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.

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Keratinocytes are mechanoresponsive to the microflow‐induced shear stress

Cited by 18 publications

References 54 publications

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

Evaluation of in vitro human skin models for studying effects of external stressors and stimuli and developing treatment modalities

Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin

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