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

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.

Design and evaluation of a skin-on-a-chip pumpless microfluidic device

“…In addition, due to the natural differences between animal and human skin physiology 26 , the results from animal model experiments, especially in the field of transdermal drug delivery, could not predict human skin responses 27 . Thus, many of the potential drugs, which show promising results in animal model studies, fail in clinical trial steps 28 .…”

Progress in the Application of 3D Skin Models for Cosmetic Assessment

“…In summary, there is still a long way to go to mimic the complex structure of living skin. For cosmetic applications, the 3D skin model needs to be continuously optimized for the following reasons: 1) Consistency: The primary cells used to construct the 3D skin model are not derived from the same donor, and there are differences in the measurement indicators of the models [78,79]. 2) Baseline: the critical baseline for cosmetic applications through different commercial skin models, and the commonly accepted scaling law still needs to be developed [80].…”

Advancements in microfluidics for skin cosmetic screening

“…87 Notably, the microbiome is often forgotten in skin-on-achip models and there is still a lack of reports on integrated microbiota. 88 It is well known that human skin is chronically exposed to air and thus colonized by numerous microorganisms, and the host and symbiotic microbiota rely on immune cell and molecular network interactions to establish and maintain healthy skin homeostasis. 89 Integrating microbiota in skin-on-a-chip devices helps to fully replicate human skin models and construct more realistic human skin equivalents.…”