Development of 3D skin-equivalent in a pump-less microfluidic chip

Song, Hee-Jung; Lim, Ho Young; Chun, Wook; Choi, Kyung Chan; Lee, Tai-Yong; Sung, Jong Hwan; Sung, Gun Yong

doi:10.1016/j.jiec.2017.11.022

Cited by 43 publications

(39 citation statements)

References 22 publications

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“…In addition, full thickness 3D skin equivalents that consist of both an epidermal and dermal layer are a better representation of the human skin [8]. Microfabricated cell systems, however, provide arguably an even better model for mimicking in vivo skin processes including vasculature and thus allowing for the testing of absorption of pharmaceutical products [50][51][52]. Additionally, 3D bioprinting provides greater accuracy in placement of cells and extracellular matrices along with the potential of imbedding vasculature in the skin construct as well as having great plasticity [54].…”

Section: Resultsmentioning

confidence: 99%

“…A comparison of on-chip cell cultures to traditional transwell skin cultures was completed by Song et al, [52] in which a static (no flow) chip, dynamic (flow, based on a gravity flow system) chip, and transwell skin equivalents were compared. The comparison revealed that the static chip was not the ideal method as differentiation of skin did not occur and the epidermis was not attached by the end of 1 week [52]. It is thought that this is a result of lack of flow or perfusion in the static chip and thus insufficient flow of nutrients for the growth of the cells [52].…”

Section: On-chip Skin Culturementioning

confidence: 99%

“…The comparison revealed that the static chip was not the ideal method as differentiation of skin did not occur and the epidermis was not attached by the end of 1 week [52]. It is thought that this is a result of lack of flow or perfusion in the static chip and thus insufficient flow of nutrients for the growth of the cells [52]. Thus an advantage to using microfabricated skin cell cultures vs. typical 3D cell cultures is the provision of microfluidics which can aid in the supply of essential nutrients for the growth and differentiation of skin cells as well as more closely mimicking in vivo processes such as vasculature [51,52].…”

Section: On-chip Skin Culturementioning

confidence: 99%

“…However, regardless of their improvements vs. the 2D cell cultures, typically 3D cell cultures still lack in their ability to provide key functions such as cellular waste removal [7]. Microfabricated cell cultures or on-chip cell cultures are advantageous in this instance as they provide microfluidic channels that enable the flow of nutrients and waste removal as well as the ability to mimic vasculature [51,52]. Thus microfabricated 3D cell cultures are arguably the in vitro method of cell cultures that most closely mimic in vivo processes [50].…”

Section: D Vs 3d Cell Cultures: Advantages and Disadvantagesmentioning

confidence: 99%

“…With respect to skin cell cultures, those that are 3D have the advantages of containing a stratum corneum and thus the ability of testing pharmaceutical products on the stratum corneum • Do not always provide an accurate representation of in vivo processes [7] • Use of a single cell type, [80] for example with skin cell cultures, the use of keratinocytes only [8] • No cell-to-cell or cell-to-extracellular matrix interactions [5,80] 3D cell cultures • Better imitation of in vivo processes [7] • Better understanding of the interactions that take place between cell-to-cell and cell-to-extracellular matrix [7] • Possess gene expression abilities, thus mimicking in vivo processes [83] • Microfabricated cell cultures or on-chip cell cultures provide microfluidic channels that enable the flow of nutrients and waste removal as well as the ability to mimic vasculature [51,52] • 3D skin cultures have a stratum corneum and thus the ability of testing pharmaceutical products on the stratum corneum as a skin barrier [40] • Longer skin cell culture use between 10 and 30 days [40]; more recent human skin equivalent (HSE) cultures can even be used for up to 20 weeks [41] • 3D bioprinting provides greater accuracy in placement of cells and extracellular matrix, potential of imbedding vasculature in the skin construct and have great plasticity [54] • 3D bioprinted skin models provide more uniform models vs. manually developed skin models [55] • Typically lack in their ability to provide key functions such as cellular waste removal [7] • Cost associated with developing cultures [40,54] as a skin barrier [40]. Other advantages to the use of 3D skin cell cultures include longer cell culture use between 10 and 30 days [40].…”

Section: D Vs 3d Cell Cultures: Advantages and Disadvantagesmentioning

confidence: 99%

See 4 more Smart Citations

2D vs. 3D Cell Culture Models for In Vitro Topical (Dermatological) Medication Testing

Teimouri¹,

Yeung²,

Agu³

2019

Cell Culture

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Due to ethical concerns regarding animal testing, alternative methods have been in development to test the efficacy and safety of pharmaceutical products and medications, specifically topical (dermatological) medications. Two-dimensional (2D) and three-dimensional (3D) skin cell cultures are examples of in vitro methods used as an alternative to animal testing. The first skin cells cultured were keratinocytes, a type of cell predominantly in the epidermal layer of the skin. However, with differences in skin characteristics and pathophysiology of different skin conditions, various skin cell cultures and models to better mimic these differences have been developed. These cell cultures include not only keratinocytes but also other skin cell types, such as fibroblasts, which are predominantly in the dermal layer of the skin, and certain immune cells and even melanocytes. To have a better understanding of the type of cell cultures used for testing dermatological products, this chapter aims to outline the differences between 2D and 3D skin cell cultures while considering the advantages and disadvantages of each culture. Different types of cell culture models used for wound healing and for inflammatory skin conditions such as psoriasis will also be discussed.

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Section: Resultsmentioning

confidence: 99%

Section: On-chip Skin Culturementioning

confidence: 99%

Section: On-chip Skin Culturementioning

confidence: 99%

Section: D Vs 3d Cell Cultures: Advantages and Disadvantagesmentioning

confidence: 99%

Section: D Vs 3d Cell Cultures: Advantages and Disadvantagesmentioning

confidence: 99%

See 3 more Smart Citations

2D vs. 3D Cell Culture Models for In Vitro Topical (Dermatological) Medication Testing

Teimouri¹,

Yeung²,

Agu³

2019

Cell Culture

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Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

et al. 2019

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The major motivation is to better mimic human physiology and functions at multiscales from the molecular to the cellular, tissue, organ or even whole organism level. Current model systems primarily rely on the monolayer cell cultures and animal models. Simplistic monolayer cultures have their advantages, but they are often significantly different in gene expression, epigenetics, and cell function compared to native 3D tissues. [1,2] Also, they often lack cell-cell and cell-matrix interactions, [2,3] leading to the absence of tissue specific properties. Although animal models are widely used in biomedical research, they fail to faithfully predict human responses in a physiologically relevant manner due to the significant species divergences. [4] The limitations of these systems have provided an impetus for the development of alternative cell-based 3D models in vitro that better resemble the complex functionalities of living organs. Over the last several years, organoids and organ-on-a-chip (OOC), representing the major technological breakthrough, have emerged as two distinct model systems to achieve the same goal of building 3D organotypic models in vitro by bridging the gap between animal models and monolayer cultures. These engineered models are different in terms of cell source, tissue composition, architectural variability, functional features, scales, cellular fidelity, etc. Organoids, primarily evolving from developmental principles, refer to 3D multicellular tissues by self-organization of stem cells or organ-specific progenitors, which can recapitulate the intricate architectures and functionalities of in vivo organs. [5][6][7] Recent breakthroughs in organoid technology have enabled the successful generation of a variety of human organoids, such as the brain, [8,9] intestine, [10,11] liver, [12] kidney, [13,14] lung, [15] etc. These near physiological 3D organoids have garnered momentum for their potential applications in human organ development and disease modeling, drug screening and regenerative medicine. The explosion of organoids research has been catalyzed by the significant progress of stem cell biology and availability of human stem cells. In contrast, the OOC, relying on the bioengineering design principle, is a miniaturized in vitro model that can recreate the functional units of living organs on a microfluidic cell culture device using predifferentiated cells, often cell lines. [1,16] The OOC is primarily evolved from the convergence of tissue engineering and microfabricated technologies, which is characterized by the capability to simulate cellular microenvironment by precise control over fluid flow, mechanical forces and biochemical factors. [4,17] Remarkable progress has been made Significant advances in materials, microscale technology, and stem cell biology have enabled the construction of 3D tissues and organs, which will ultimately lead to more effective diagnostics and therapy. Organoids and organs-on-a-chip (OOC), evolved from developmental biology and bioengineering principles, have e...

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Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue

Kwak

Jin

Kim³

et al. 2020

Biotech & Bioengineering

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There is a considerable need for cell‐based in vitro skin models for studying dermatological diseases and testing cosmetic products, but current in vitro skin models lack physiological relevance compared to human skin tissue. For example, many dermatological disorders involve complex immune responses, but current skin models are not capable of recapitulating the phenomena. Previously, we reported development of a microfluidic skin chip with a vessel structure and vascular endothelial cells. In this study, we cocultured dermal fibroblasts and keratinocytes with vascular endothelial cells, human umbilical vascular endothelial cells. We verified the formation of a vascular endothelium in the presence of the dermis and epidermis layers by examining the expression of tissue‐specific markers. As the vascular endothelium plays a critical role in the migration of leukocytes to inflammation sites, we incorporated leukocytes in the circulating media and attempted to mimic the migration of neutrophils in response to external stimuli. Increased secretion of cytokines and migration of neutrophils was observed when the skin chip was exposed to ultraviolet irradiation, showing that the microfluidic skin chip may be useful for studying the immune response of the human tissue.

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Development of 3D skin-equivalent in a pump-less microfluidic chip

Cited by 43 publications

References 22 publications

2D vs. 3D Cell Culture Models for In Vitro Topical (Dermatological) Medication Testing

2D vs. 3D Cell Culture Models for In Vitro Topical (Dermatological) Medication Testing

Advances in Hydrogels in Organoids and Organs‐on‐a‐Chip

Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue

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