Side-effect test of sorafenib using 3-D skin equivalent based on microfluidic skin-on-a-chip

Jeon, Hosang; Kim, Kyunghee; Choi, Kyung Chan; Sung, Gun Yong

doi:10.1016/j.jiec.2019.09.044

Cited by 36 publications

(21 citation statements)

References 30 publications

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“…It is a more convenient system without the drawback of having to rely on a drive pump and without the problems caused by air bubbles, which is very problematic in tube experiments. Three type I collagen studies have confirmed that rat-tail collagen is the most appropriate scaffold [ 32 ] and that pumpless SOC produces anticancer-drug-induced side effects on the skin [ 33 ] and anti-aging effects. We have reported the effects of curcuma longa leaf extract (CLLE) [ 34 ] and CoQ10 drugs [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Kim

et al. 2021

IJMS

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Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.

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Section: Introductionmentioning

confidence: 99%

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Kim

et al. 2021

IJMS

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“…This skin-on-a-chip model was further used for different drug testing. Jeon et al 76 studied the dermatological side effects of sorafenib, a therapeutic agent used for hepatocellular carcinoma treatments, administering the drug on the skin-on-a-chip model. It was also used by Kim et al 77 to study the effect of an extract coming from Curcuma longa leaves on skin forming and differentiation, finding anti-ageing effects [ Fig.…”

Section: Skin-on-a-chipmentioning

confidence: 99%

Skin-on-a-chip models: General overview and future perspectives

et al. 2021

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Over the last few years, several advances have been made toward the development and production of in vitro human skin models for the analysis and testing of cosmetic and pharmaceutical products. However, these skin models are cultured under static conditions that make them unable to accurately represent normal human physiology. Recent interest has focused on the generation of in vitro 3D vascularized skin models with dynamic perfusion and microfluidic devices known as skin-on-a-chip. These platforms have been widely described in the literature as good candidates for tissue modeling, as they enable a more physiological transport of nutrients and permit a high-throughput and less expensive evaluation of drug candidates in terms of toxicity, efficacy, and delivery. In this Perspective, recent advances in these novel platforms for the generation of human skin models under dynamic conditions for in vitro testing are reported. Advances in vascularized human skin equivalents (HSEs), transferred skin-on-a-chip (introduction of a skin biopsy or a HSE in the chip), and in situ skin-on-a-chip (generation of the skin model directly in the chip) are critically reviewed, and currently used methods for the introduction of skin cells in the microfluidic chips are discussed. An outlook on current applications and future directions in this field of research are also presented.

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“…A 3D skin equivalent is superior to the 2D model in that it can mimic the 3D structure of the epidermis and dermis to create environmental conditions similar to human skin [5]. Recently, research on skin-on-a-chip constructs using a gravity flow system without a pump and tube to supply culture medium has also been conducted [11][12][13]. This study used a pumpless skin-on-a-chip, which provides the same physiological conditions as human skin.…”

Section: Contraction Of 3d Co-cultured Human Skin Equivalents By a Pumentioning

confidence: 99%

Coenzyme Q10 Efficacy Test for Human Skin Equivalents Using a Pumpless Skin-On-A-Chip System

Kim

Sung

2020

IJMS

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A human skin equivalent (HSE) composed of the epidermis and dermis is cultured using a pumpless skin-on-a-chip system to supply cultures the desired flow rate using gravity flow without a pump or an external tube connection. Coenzyme Q10 efficacy is tested by adjusting its concentration, as it is known to have anti-aging and antioxidant effects in culture solutions. The relationship between the contraction rate of a full-thickness human skin equivalent and secreted transforming growth factor (TGF) β-1 is analyzed via enzyme-linked immunosorbent assay (ELISA). Following hematoxylin and eosin (H&E) staining, an image of the skin equivalent is analyzed to measure the epidermal layer’s thickness. The cell density and differentiation of the dermis layer are investigated. Gene and protein expression in the dermal and epidermal layers are quantitatively analyzed using quantitative real time polymerase chain reaction (qPCR) and immunohistochemical staining. As the coenzyme Q10 treatment concentration increased, the number of cells per unit area and the thickness of the epidermal layer increased, the expression level of filaggrin increased, and the contraction rate of full-thickness HSE was proportional to the amount of TGF β-1 secreted.

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Side-effect test of sorafenib using 3-D skin equivalent based on microfluidic skin-on-a-chip

Cited by 36 publications

References 30 publications

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Skin-on-a-chip models: General overview and future perspectives

Coenzyme Q10 Efficacy Test for Human Skin Equivalents Using a Pumpless Skin-On-A-Chip System

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