The role of skin in the human body is indispensable, serving as a barrier, moderating homeostatic balance, and representing a pronounced endpoint for cosmetics and pharmaceuticals. Despite the extensive achievements of in vitro skin models, they do not recapitulate the complexity of human skin; thus, there remains a dependence on animal models during preclinical drug trials, resulting in expensive drug development with high failure rates. By imparting a fine control over the microenvironment and inducing relevant mechanical cues, skin‐on‐a‐chip (SoC) models have circumvented the limitations of conventional cell studies. Enhanced barrier properties, vascularization, and improved phenotypic differentiation have been achieved by SoC models; however, the successful inclusion of appendages such as hair follicles and sweat glands and pigmentation relevance have yet to be realized. The present Review collates the progress of SoC platforms with a focus on their fabrication and the incorporation of mechanical cues, sensors, and blood vessels.

Skin is exposed to a variety of potential stressors and stimulators that may impact homeostasis, healing, tumor development, inflammation, and irritation. As such it is important to understand the impact that these stimuli have on skin health and function, and to develop therapeutic interventions. Animal experiments have been the gold standard for testing the safety and efficacy of therapeutics and observing disease pathology for centuries. However, complex ethics, costs, time consumption, and interspecies variation limit the transferability of results to humans and reduce their repeatability and reliability. Furthermore, traditional 2D cell studies are not representative of human tissue. Skin tissue is a dynamic environment, and when cells are isolated in unphysiologically stiff, static petri dishes their behavior, and phenotypic expression is altered. Increasingly complex in vitro models of human skin, including organoids, 3D bioprinting, and skin-on-a-chip platforms, present the opportunity to gain insight into how stressors affect tissue at a cellular level in a controlled and repeatable environment. This insight can be leveraged to further understand pathological skin conditions and better formulate and validate drugs and therapeutics. Here, we will discuss the application of in vitro skin modeling to investigating the effects of mechanical, electromagnetic, and chemical stressors on skin. 3D bioprinting, drug development, in vitro, organoid, skin model, skin-on-chip This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Photobiomodulation (PBM) refers to the use of light to modulate cellular processes, and has demonstrated utility in improving wound healing outcomes, and reducing pain and inflammation. Despite the potential benefits of PBM, the precise molecular mechanisms through which it influences cell behavior are not yet well understood. Inconsistent reporting of key light parameters has created uncertainty around optimal exposure profiles. In addition, very low intensities of light, < 0.1 J/cm2, have not been thoroughly examined for their use in PBM. Here, we present a custom-made compact, and modular LED-based exposure system for studying the effects of very low-intensity visible light (cell proliferation, migration, ROS production, and mitochondrial membrane potential) of three different wavelengths in a parallel manner. The device allows for six repeats of three different exposure conditions plus a non-irradiated control on a single 24-well plate. The immortalised human keratinocyte cell line, HaCaT, was selected as a major cellular component of the skin epidermal barrier. Furthermore, an in vitro wound model was developed by allowing the HaCaT to form a confluent monolayer, then scratching the cells with a pipette tip to form a wound. Cells were exposed to yellow (585 nm, 0.09 mW, ~ 3.7 mJ/cm2), orange (610 nm, 0.8 mW, ~ 31 mJ/cm2), and red (660 nm, 0.8 mW, ~ 31 mJ/cm2) light for 10 min. 48 h post-irradiation, immunohistochemistry was performed to evaluate cell viability, proliferation, ROS production, and mitochondrial membrane potential. The results demonstrate increased proliferation and decreased scratch area for all exposure conditions, however only red light increased the mitochondrial activity. Oxidative stress levels did not increase for any of the exposures. The present exposure system provides opportunities to better understand the complex cellular mechanisms driven by the irradiation of skin cells with visible light.