Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion

Ataç, Beren; Wagner, Ilka; Horland, Reyk; Lauster, Roland; Marx, Uwe; Tonevitsky, Alexander G.; Azar, Reza P.; Lindner, G

doi:10.1039/c3lc50227a

Cited by 238 publications

(173 citation statements)

References 23 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…The MOC platform described here represents a stable and powerful tool for cultivating tissues of various origins at dynamic medium flow conditions over prolonged culture periods 10,16 . In this example, the platform was used to cultivate primary cells (HDMEC), tissue equivalents generated from a cell line (liver aggregates), and a coculture of the aforementioned with a tissue biopsy.…”

Section: Discussionmentioning

confidence: 99%

The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture

Materne

Maschmeyer

Lorenz

et al. 2015

JoVE

Self Cite

View full text Add to dashboard Cite

The ever growing amount of new substances released onto the market and the limited predictability of current in vitro test systems has led to a high need for new solutions for substance testing. Many drugs that have been removed from the market due to drug-induced liver injury released their toxic potential only after several doses of chronic testing in humans. However, a controlled microenvironment is pivotal for longterm multiple dosing experiments, as even minor alterations in extracellular conditions may greatly influence the cell physiology. We focused within our research program on the generation of a microengineered bioreactor, which can be dynamically perfused by an on-chip pump and combines at least two culture spaces for multi-organ applications. This circulatory system mimics the in vivo conditions of primary cell cultures better and assures a steadier, more quantifiable extracellular relay of signals to the cells.For demonstration purposes, human liver equivalents, generated by aggregating differentiated HepaRG cells with human hepatic stellate cells in hanging drop plates, were cocultured with human skin punch biopsies for up to 28 days inside the microbioreactor. The use of cell culture inserts enables the skin to be cultured at an air-liquid interface, allowing topical substance exposure. The microbioreactor system is capable of supporting these cocultures at near physiologic fluid flow and volume-to-liquid ratios, ensuring stable and organotypic culture conditions. The possibility of long-term cultures enables the repeated exposure to substances. Furthermore, a vascularization of the microfluidic channel circuit using human dermal microvascular endothelial cells yields a physiologically more relevant vascular model.

show abstract

Section: Discussionmentioning

confidence: 99%

The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture

Materne

Maschmeyer

Lorenz

et al. 2015

JoVE

Self Cite

View full text Add to dashboard Cite

show abstract

“…This affects cell-cell communications and local concentrations of secreted ligands of tissues [73]. The presence of flow also allows the study of circulating cells, such as circulating breast cancer cells with microvascular endothelium at potential sites of metastasis [83] or immune cells [84].…”

Section: Organ-on-a-chipmentioning

confidence: 99%

“…Also, human induced pluripotent stem cells provide a source to mimic healthy and diseased skin models as they can be differentiated into keratinocytes [70], fibroblasts [71], melanocytes [72] and endothelial cells [67]. Besides simplified models with dermis and epidermis, also more complex models with hair follicles and adipocytes [73], immune cells [74] and features resembling sweat gland pores [75] exist. In addition, skin-on-a-chip can be expanded to multiple organ chips to test drug metabolism.…”

Section: Organ-on-a-chipmentioning

confidence: 99%

In vitro skin three-dimensional models and their applications

Klicks

Molitor

Ertongur-Fauth

et al. 2017

JCB

View full text Add to dashboard Cite

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.

show abstract

“…In a recent paper, the use of a multi-organ-chip bioreactor platform was reported to improve the spatiotemporal control of the cellular microenvironment compared to traditional in vitro assays. 79 …”

Section: 66mentioning

confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

View full text Add to dashboard Cite

The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

show abstract

Skin and hair on-a-chip: in vitro skin models versus ex vivo tissue maintenance with dynamic perfusion

Cited by 238 publications

References 23 publications

The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture

The Multi-organ Chip - A Microfluidic Platform for Long-term Multi-tissue Coculture

In vitro skin three-dimensional models and their applications

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

Contact Info

Product

Resources

About