Skin-on-a-chip model simulating inflammation, edema and drug-based treatment

Wufuer, Maierdanjiang; Lee, Geon Hui; Hur, Woojune; Jeon, Byoungjun; Kim, Byung Jun; Choi, Tae Hyun; Lee, Sang Hoon

doi:10.1038/srep37471

Cited by 275 publications

(197 citation statements)

References 51 publications

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“…The importance of mechanical forces for tissue development has been repeatedly demonstrated for several organs including skin, ligaments and arteries . This limitation can be addressed by advances in, for example, microfluidic cell cultures or the establishment of dynamic perfusion chambers . Approaches towards the inclusion of vasculature include the generation of in vivo like vascularized skin equivalents with a perfused vascular network.…”

Section: Limitations Of In Vitro Models and Necessary Improvementsmentioning

confidence: 99%

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Löwa

Jevtić

Gorreja

et al. 2018

Experimental Dermatology

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Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies-related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). K E Y W O R D S3R approach, atopic dermatitis, preclinical dermatology, skin equivalents, skin model

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Section: Limitations Of In Vitro Models and Necessary Improvementsmentioning

confidence: 99%

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Löwa

Jevtić

Gorreja

et al. 2018

Experimental Dermatology

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“…For such purpose, the skin‐on‐a‐chip technology could provide a standardized, dynamic, and medium to high‐throughput model. This technology enables a dynamic cell culture on a microfluidic device that can be constructed of several layers separated by transparent, porous membranes to allow cellular communication and interaction to study inflammation and drug treatment . Ultimately, in vitro models for psoriasis will certainly refine and reduce experimental animal models but perhaps may never fully replace them.…”

Section: The Perfect In Vitro Psoriasis Skin Model: Are We There Yet?mentioning

confidence: 99%

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

Niehues

Bogaard

2018

Experimental Dermatology

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Psoriasis is a common chronic inflammatory disease affecting about 1%-2% of today's Western population.[1] Several subtypes of psoriasis are known, but herein we focus on psoriasis vulgaris which is most prevalent and phenotypically characterized by sharply demarcated plaques covered with white scales. The pathogenesis of psoriasis is complex and exact mechanisms of disease onset and manifestation remain unknown. However, it is known that psoriasis cannot be attributed to a single risk factor or insult but is likely caused by the interaction of environmental and genetic factors. Based on a number of genomewide association studies (GWAS) and meta-analyses thereof, more than 60 susceptibility loci have been identified that account for 20%-25% of psoriasis heritability. [2][3][4][5][6][7] Although psoriasis has been regarded as an (auto) immune disease for a long time, an increasing body of evidence directs towards a combined role for the innate and adaptive immune system in combination with tissue specific epidermal factors. AbstractPsoriasis is a common chronic inflammatory skin disease with a significant socioeconomic impact that can greatly affect the patients' quality of life. The prevailing dogma in the aetiology and pathophysiology of this complex disease is that skin cells, immune cells and environmental factors contribute to psoriatic skin inflammation.For a better understanding of the disease pathogenesis, models are required that mimic the disease and which can be used to develop therapeutics. Over the last decades, in vitro human reconstructed skin models have been widely used in dermatological research and have also been developed to mimic psoriatic skin. This viewpoint summarizes the most commonly used in vitro models and the latest accomplishments for the combination of the dermal and epidermal compartments with other cell types

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“…Accordingly, Maschmeyer et al and Wagner et al engineered two and four organ chips with intestine, liver, skin and kidney [76][77][78]. Furthermore, disease models simulating inflammation and edema exist [79].…”

Section: Organ-on-a-chipmentioning

confidence: 99%

“…However, PDMS has the disadvantage that it might absorb small molecules such as drugs [86]. Molecular analysis, like PCR, is feasible [79]. The main limitations are the high costs of this system and the demanding skills due to its complex assembly.…”

Section: Organ-on-a-chipmentioning

confidence: 99%

In vitro skin three-dimensional models and their applications

Klicks

Molitor

Ertongur-Fauth

et al. 2017

JCB

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Abstract. Skin fulfils a plethora of eminent physiological functions ranging from physical barrier over immunity shield to the interface mediating social interaction. Prone to several acquired and inherited diseases, skin is therefore a major target of pharmaceutical and cosmetic research. The lack of similarity between human and animal skin and rising ethical concerns in the use of animal models have driven the search for novel realistic three-dimensional skin models. This review provides a survey of contemporary skin models and compares them in terms of applicability, reliability, cost and complexity.Keywords: Skin, phenotypic screening, 3D models, pharmaceutical research Skin -composition and functionHuman skin covers an area of almost 2 m 2 in the adult and consists of the three major layers, subcutis, dermis, and epidermis. The subcutis is composed of adipose and epithelial cells. It harbours blood vessels, neurites of peripheral neurons, Vater-Pacini mechanosensors, and, partially, also sweat glands and hair follicles. It connects the skin to periosteum and fascia, absorbs forces, and mediates thermal insulation. The dermis supplies the epidermis with mechanical support and nutrients. It is stratified into an inner, reticular, and an outer, papillary, zone. The dermis houses most sebaceous glands, sweat glands, hair follicles, smooth muscle cells, and capillary beds and, thus, regulates skin moisture, body temperature, and performs the secretory function of skin. The papillary layer is characterized by relatively loose connective tissue, where Meissner corpuscles sense touch. Immune cells, particularly mast cells and dendritic cells, are patrolling in the papillary layer and mediate local inflammatory reactions and immune surveillance. Finally, dermal fibroblasts secrete extracellular matrix (ECM) and basement membrane components. These are primarily collagens I and III, and a proteoglycan-rich ground substance [1]. The resulting ECM mediates tensile strength of the dermis. The dermo-epidermal junction is centered around a special basement membrane. This is composed of a laminin/collagen IV scaffold and further typical basement membrane components such as perlecans and nidogens [1].The epidermis is a squamous epithelium of 50-100 m thickness. It is devoid of blood vessels but contains keratinocytes, Merkel cell mechanosensors, Langerhans immune cells, and melanocytes. The 1 These authors contributed equally.

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Skin-on-a-chip model simulating inflammation, edema and drug-based treatment

Cited by 275 publications

References 51 publications

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Past, present and future of in vitro 3D reconstructed inflammatory skin models to study psoriasis

In vitro skin three-dimensional models and their applications

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