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Review
. 2024 Sep 18;5(1):100315.
doi: 10.1016/j.xjidi.2024.100315. eCollection 2025 Jan.

Advances in Microengineered Platforms for Skin Research

Sireesh Kumar Teertam  1   2 , Vijayasaradhi Setaluri  1   2   3 , Jose M Ayuso  1   2   4
Affiliations
Review

Advances in Microengineered Platforms for Skin Research

Sireesh Kumar Teertam et al. JID Innov. .

Abstract

The skin plays a critical role in human physiology, acting both as a barrier to environmental insults and as a window to environmental stimuli. Disruption of this homeostasis leads to numerous skin disorders. Human and animal skin differ significantly, limiting the translational potential of animal-based investigations to advance therapeutics to human skin diseases. Hence, there is a critical need for physiologically relevant human skin models to explore novel treatment strategies. Recent advances in microfluidic technologies now allow design and generation of organ-on-chip devices that mimic critical features of tissue architecture. Skin-on-a-chip and microfluidic platforms hold promise as useful models for diverse dermatology applications. Compared with traditional in vitro models, microfluidic platforms offer improved control of fluid flow, which in turn allows precise manipulation of cell and molecular distribution. These properties enable the generation of multilayered in vitro models that mimic human skin structure while simultaneously offering superior control over nutrient and drug distribution. Researchers have used microfluidic platforms for a variety of applications in skin research, including epidermal-dermal cellular crosstalk, cell migration, mechanobiology, microbiome-immune response interactions, vascular biology, and wound healing. In this review, we comprehensively review state-of-the-art microfluidic models for skin research. We discuss the challenges and promise of current skin-on-a-chip technologies and provide a roadmap for future research in this active field.

Keywords: In vitro culture; Microfluidics; Organ-on-a-chip; Skin models.

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Figures

Figure 1
Figure 1
Different skin research platforms. Overview of preclinical and clinical skin research models used to study skin biology is presented. Shown is an illustration of multiple model systems currently used (in vitro/microfluidics/in vivo platforms) to study skin biology and skin pathologies with their advantages and disadvantages. (a) The illustration shows conventional 2D cell culture system with different skin cells, the advantages, and disadvantages of cell culture. (b) Schematic shows the construction of SoC platform using skin cells or direct skin biopsy and the advantages and disadvantages of microfluidic SoC platforms. (c) In vivo skin research models and their advantages and disadvantages. The schematic was created using BioRender. 2D, 2-dimensional; SoC, skin-on-a-chip.
Figure 2
Figure 2
Microfluidic device design, fabrication, and operation. Simple microfluidic devices can be designed in user-friendly software such as Adobe Illustrator or MS PowerPoint, whereas devices with complicated designs and intricate 3D features often require specialized software used in engineering (eg, AutoCAD, Solidworks). Once the microdevice design is finalized, there are several fabrication techniques that can be used, including 3D printing, micromilling, or optical lithography. Each technique provides a unique set of advantages and limitations. Finally, the desired biological elements such as cells or ECM proteins are loaded into the microfluidic device by pipetting them through the inlets. The microdevice is now ready for biological analysis using a broad range of techniques such as optical microscopy (eg, fluorescence, confocal, multiphoton) or molecular analysis (eg, RNA-seq, mass spectrometry, nuclear magnetic resonance). 3D, 3-dimensional; ECM, extracellular matrix; MS, Microsoft; PDMS, polydimethylsiloxane; RNA-seq, RNA sequencing.
Figure 3
Figure 3
Different microfluidic skin platforms and their features. The schematic diagram shows different types of microfluidic platforms (a–e) used for different skin research studies. The diagram highlights different features of the platforms that are helpful for studying different skin pathologies.
Figure 4
Figure 4
Biological functions of different microfluidic skin platforms. The schematic diagram shows the applications of different microfluidic platforms used for different skin research studies. The diagram highlights the biological function (staining and microscopy imaging) and outcome of different platforms. (a) Image representing HSE-on-a-chip platform comprised of fibroblasts and keratinocytes separated by a transmembrane. The rocking platform provides gravity-driven fluid flow and is useful for drug profiling. (b) The SoC with perfusable vascular channels comprised of keratinocytes, fibroblasts, and endothelial cells on the PDMS platform. The SoC device mainly helps in understanding barrier properties and metabolic changes. (c) The skin chip platform consists of epidermal keratinocytes and dermal fibroblasts embedded in collagen, with endothelial cells at the bottom of the device separated from the rest of the stromal cells with the help of a porous membrane. This platform is mainly helpful for toxicology, inflammatory response, and myeloid cell infiltration. (d) The microfluidic platform with air walls was developed to understand the interaction between skin stromal cell roles in melanomagenesis. This device is mainly composed of skin stromal cells (fibroblasts and keratinocytes) in lateral chambers and melanoma cells in the central chamber. The liquid flow between 2 channels allows for communication/exchange of secretory factors. This platform is mainly useful in studying cancer cell–stromal cell communication and real-time imaging of cells as they move in lateral directions. (e) The PDMS-based microfluidic platform with innervated epidermis was comprised of epidermal keratinocytes in the epidermal channel and sensory neurons in the soma chamber separated by acellular dermal layer/ECM. This platform is useful in understanding cell–cell communication, cell–matrix communication, and sensory response (Abaci et al, 2015; Ahn et al, 2023; Ayuso et al, 2021b; Kwak et al, 2020; Mori et al, 2017). HSE, human skin equivalent; HUVEC, human umbilical vein endothelial cell; PDMS, polydimethylsiloxane; SoC, skin-on-a-chip.
Figure 5
Figure 5
Comparison of transferred skin-on-a-chip with in situ skin-on-a-chip platforms. Microfluidic devices for skin biology can be divided into 2 different categories. Transferred skin-on-a-chip relies of culturing skin tissue (eg, skin biopsy) in a microfluidic device that will provide culture medium, nutrients, drugs, or other cells (eg, immune cells) to the skin biopsy. This approach is preferred when the tissue integrity must be preserved and allows researchers to study complex skin structures such as sweat glands or hair follicles, which are still challenging to generate in vitro. The second category is in situ skin-on-a-chip, which relies on a bottom-up approach where the desired cells (eg, keratinocytes, fibroblasts, melanocytes) are assembled into a 3D structure that mimics the skin architecture. This method offers superior control over tissue configuration and provides the user with improved capacity to manipulate the tissue microenvironment. 3D, 3-dimensional.
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