Recent advances in in vitro skin-on-a-chip models for drug testing

ABSTRACT

Introduction

The skin is an organ that has the largest surface area and provides a barrier against external environment. While providing protection, it also interacts with other organs in the body and has implications for various diseases. Development of physiologically realistic in vitro models of the skin in the context of the whole body is important for studying these diseases and will be a valuable tool for pharmaceutical, cosmetics, and food industry.

Area covered

This article provides an overview of the skin structure, physiology, as well as drug metabolism in the skin, and dermatological diseases. We summarize various in vitro skin models currently available, as well as novel in vitro models based on organ-on-a-chip technology. We also explain the concept of multi-organ-on-a-chip and describe recent developments in this field aimed at recapitulating the interaction of the skin with other organs in the body.

Expert opinion

Recent developments in the organ-on-a-chip field have enabled the development of in vitro model systems that resemble human skin more closely than conventional models. In the near future, we will be seeing various model systems that allow researchers to study complex diseases in a more mechanistic manner, which will help the development of new pharmaceuticals for such diseases.

KEYWORDS:

• human skin
• skin diseases
• drug metabolism
• organ-on-a-chip
• skin-on-a-chip
• multi-organ-on-a-chip

Article highlights

• Although skin metabolism affects the effectiveness of transdermal or skin topical drugs, drug metabolism in the skin is less well understood than hepatic metabolism, requiring a reliable in vitro skin model.

• Compared to the conventional skin equivalents, skin-on-a-chip models more closely recapitulate human skin, having them promising drug testing or disease models.

• One way to classify skin-on-a-chip models is the type of skin model. Hydrogel matrix-based skin, transferred skin, and multiple 2D layered skin models were integrated into the microfluidic device.

• In addition to the dynamic perfusion, recent skin-on-a-chip models are integrated with vasculature, contracting matrix, immune system, and cyclic tensile stimulation to closely mimic the real human skin.

• Multi-organ-on-a-chips with skin model successfully recapitulates the multi-organ axis to study organ–organ interaction in a wide range of situations, including the administration of skin topical drugs.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership, or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported in part by the Technology development Program (S3316767) by Korea Technology and Information Promotion Agency, Basic Research Lab (2022R1A4A2000748), Bio & Medical Technology Development Program (2022M3A9B6018217), Grant 2022R1F1A1073540 by National Research Foundation of Korea, Technology Innovation Program (20008414), and the Alchemist Project of the Korea Evaluation Institute of Industrial Technology (KEIT 20018560, NTIS 1415180625) by the Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea. It was also supported by the Hongik University Research Fund