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Review
. 2022 Jul 6;14(7):1417.
doi: 10.3390/pharmaceutics14071417.

Modeling an Optimal 3D Skin-on-Chip within Microfluidic Devices for Pharmacological Studies

Estibaliz Fernandez-Carro  1 , Maricke Angenent  1 , Tamara Gracia-Cazaña  2 , Yolanda Gilaberte  2 , Clara Alcaine  1   3 , Jesús Ciriza  1   3   4
Affiliations
Review

Modeling an Optimal 3D Skin-on-Chip within Microfluidic Devices for Pharmacological Studies

Estibaliz Fernandez-Carro et al. Pharmaceutics. .

Abstract

Preclinical research remains hampered by an inadequate representation of human tissue environments which results in inaccurate predictions of a drug candidate's effects and target's suitability. While human 2D and 3D cell cultures and organoids have been extensively improved to mimic the precise structure and function of human tissues, major challenges persist since only few of these models adequately represent the complexity of human tissues. The development of skin-on-chip technology has allowed the transition from static 3D cultures to dynamic 3D cultures resembling human physiology. The integration of vasculature, immune system, or the resident microbiome in the next generation of SoC, with continuous detection of changes in metabolism, would potentially overcome the current limitations, providing reliable and robust results and mimicking the complex human skin. This review aims to provide an overview of the biological skin constituents and mechanical requirements that should be incorporated in a human skin-on-chip, permitting pharmacological, toxicological, and cosmetic tests closer to reality.

Keywords: ECM; TEER; cosmetic test; dermatology; immune system; microbiome; microfluidic devices; pharmacological test; skin-on-chip; toxicological test.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the different skin layers. Adapted from ‘Anatomy of the skin’, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates, accessed on 9 June 2022.
Figure 2
Figure 2
Schematic representation of SoC approaches. Created with BioRender.com.
Figure 3
Figure 3
Skin model recapitulating full skin thickness with labeled epidermal layer formed by HaCat cells on top (yellow) and labeled dermal layer formed by primary dermal fibroblast (blue) below within a microfluidic device.
Figure 4
Figure 4
Flow inducing laminar (A), pulsatile (B), or interstitial (C) shear stress. Created with BioRender.com.
Figure 5
Figure 5
Methods and equipment to generate shear stress. Tilt movement in the rocker (A), external syringe pump (B), and internal pump within the chip (C). Created with BioRender.com.
Figure 6
Figure 6
Biological and mechanical requirements of an optimized SoC. Adapted from “Anatomy of the skin”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates, accessed on 27 June 2022.
See this image and copyright information in PMC

References

    1. van den Broek L.J., Bergers L.I.J.C., Reijnders C.M.A., Gibbs S. Progress and Future Prospectives in Skin-on-Chip Development with Emphasis on the use of Different Cell Types and Technical Challenges. Stem Cell Rev. Rep. 2017;13:418–429. doi: 10.1007/s12015-017-9737-1. - DOI - PMC - PubMed
    1. Kim B.S., Gao G., Kim J.Y., Cho D.-W. 3D Cell Printing of Perfusable Vascularized Human Skin Equivalent Composed of Epidermis, Dermis, and Hypodermis for Better Structural Recapitulation of Native Skin. Adv. Healthc. Mater. 2019;8:1801019. doi: 10.1002/adhm.201801019. - DOI - PubMed
    1. Wong C.-W., LeGrand C.F., Kinnear B.F., Sobota R.M., Ramalingam R., Dye D.E., Raghunath M., Lane E.B., Coombe D.R. In Vitro Expansion of Keratinocytes on Human Dermal Fibroblast-Derived Matrix Retains Their Stem-Like Characteristics. Sci. Rep. 2019;9:18561. doi: 10.1038/s41598-019-54793-9. - DOI - PMC - PubMed
    1. Risueño I., Valencia L., Jorcano J.L., Velasco D. Skin-on-a-chip models: General overview and future perspectives. APL Bioeng. 2021;5:030901. doi: 10.1063/5.0046376. - DOI - PMC - PubMed
    1. Aleemardani M., Trikić M.Z., Green N.H., Claeyssens F. The Importance of Mimicking Dermal-Epidermal Junction for Skin Tissue Engineering: A Review. Bioengineering. 2021;8:148. doi: 10.3390/bioengineering8110148. - DOI - PMC - PubMed

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