A microscale, full-thickness, human skin on a chip assay simulating neutrophil responses to skin infection and antibiotic treatments

Kim, Jae Jung; Ellett, Felix; Thomas, Carina N.; Jalali, Fahimeh; Anderson, R. Rox; Irimia, Daniel; Raff, Adam B.

doi:10.1039/c9lc00399a

Cited by 50 publications

(24 citation statements)

References 38 publications

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“…In order to study neutrophil responses to the presence of bacteria on the skin, Kim et al 68 designed a single-tissue transferred skin-on-a-chip device with two channels separated by a red blood cell filter. A fragment of a human skin biopsy (previously cultured with bacteria) was introduced in one of the channels and exposed to blood samples loaded in the other one [ Fig.…”

Section: Skin-on-a-chipmentioning

confidence: 99%

Skin-on-a-chip models: General overview and future perspectives

et al. 2021

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Over the last few years, several advances have been made toward the development and production of in vitro human skin models for the analysis and testing of cosmetic and pharmaceutical products. However, these skin models are cultured under static conditions that make them unable to accurately represent normal human physiology. Recent interest has focused on the generation of in vitro 3D vascularized skin models with dynamic perfusion and microfluidic devices known as skin-on-a-chip. These platforms have been widely described in the literature as good candidates for tissue modeling, as they enable a more physiological transport of nutrients and permit a high-throughput and less expensive evaluation of drug candidates in terms of toxicity, efficacy, and delivery. In this Perspective, recent advances in these novel platforms for the generation of human skin models under dynamic conditions for in vitro testing are reported. Advances in vascularized human skin equivalents (HSEs), transferred skin-on-a-chip (introduction of a skin biopsy or a HSE in the chip), and in situ skin-on-a-chip (generation of the skin model directly in the chip) are critically reviewed, and currently used methods for the introduction of skin cells in the microfluidic chips are discussed. An outlook on current applications and future directions in this field of research are also presented.

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Section: Skin-on-a-chipmentioning

confidence: 99%

Skin-on-a-chip models: General overview and future perspectives

et al. 2021

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“…In this study, a micro-biopsy of skin was taken from healthy human subjects, infected with S. aureus and then loaded into a chip containing two chambers: one for the skin explant and another for the addition of one drop of whole blood. Importantly, blood and skin were separated by columns selectively allowing for the autonomous migration of neutrophils in response to chemotactic signals secreted by the skin ( 126 ). As such, it may be possible to obtain minimally invasive micro-samples of skin and blood from humans enrolled in clinical trials receiving S. aureus vaccines to determine whether skin-derived and/or systemic immunity raised by a vaccine may contribute to physiologically relevant protection from S. aureus infection, using this model.…”

Section: Models For the Study Of S Aureus Infectionsmentioning

confidence: 99%

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

Clegg

Soldaini²,

McLoughlin

et al. 2021

Front. Immunol.

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Staphylococcus aureus is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against S. aureus have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as in vitro and ex vivo models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.

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“…Further, they have been used to study various aspects of cell biology ranging from adhesion, spreading, proliferation and differentiation, toxicity monitoring, cell counting and sorting, signaling mechanisms, among others. [ 214a,217g,254 ] Such a wide range of possibilities can cover all the necessary requirements for a cell biology laboratory, where in vitro study of single cells, populations of cells, tissues and even whole organs is conceivable such as vasculature‐on‐a‐chip, [ 255 ] skin‐on‐a‐chip, [ 256 ] brain‐on‐a‐chip, [ 257 ] bone‐on‐a‐chip, [ 258 ] muscle‐on‐a‐chip, [ 259 ] heart‐on‐a‐chip, [ 260 ] lung‐on‐a‐chip, [ 261 ] liver‐on‐a‐chip, [ 262 ] gut‐on‐a‐chip, [ 263 ] kidney‐on‐a‐chip, [ 264 ] multiorgans‐on‐a‐chip, [ 265 ] or tumor‐on‐a‐chip. [ 266 ] In this sense, the application of microfluidic bioreactors for cells studies is growing and expanding rapidly with continuous emergence of new designs and new microenvironments using different materials, processing techniques, and adding functional elements.…”

Section: Physically Active Bioreactors—main Typesmentioning

confidence: 99%

Physically Active Bioreactors for Tissue Engineering Applications

et al. 2020

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Tissue engineering (TE) is a dynamic and growing scientific field that merges the knowledge of different areas such as biology, physics, medicine, and engineering. [1] The TE discipline was first coined at a National Science Foundation sponsored meeting in 1987, thus originating a field that employs life sciences and engineering with the purpose of developing biologic or synthetic supports to restore, keep, or enhance tissue functions or damaged organs. [2] The classical TE approach has been mainly focusing on associating cells with a supporting matrix, also called biomaterials or scaffolds, that essentially acts as a passive template for tissue formation in vitro by allowing cells to adhere, migrate, differentiate, and produce tissue. Usually, the cells are seeded onto the scaffolds and, occasionally, growth factors are also added. The combination of cells, growth factors, and scaffold is often referred as the TE triad. [3] Nevertheless, novel approaches in TE that include the application of a biophysical stimuli to the scaffolds through the use of a bioreactor are emerging. [4] Tissue engineering (TE) is a strongly expanding research area. TE approaches require biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural tissue microenvironment. Also, the extracellular matrix serves as a structural base for cells and as a source of growth factors and biophysical cues. The 3D characteristics of the microenvironment is one of the most recognized key factors for obtaining specific cell responses in vivo, being the physical cues increasingly investigated. Supporting those advances is the progress of smart and multifunctional materials design, whose properties improve the cell behavior control through the possibility of providing specific chemical and physical stimuli to the cellular environment. In this sense, a varying set of bioreactors that properly stimulate those materials and cells in vitro, creating an appropriate biomimetic microenvironment, is developed to obtain active bioreactors. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the smart materials type used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells/ tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent a growing and interesting field that hold great promise for achieving suitable TE strategies.

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A microscale, full-thickness, human skin on a chip assay simulating neutrophil responses to skin infection and antibiotic treatments

Abstract: Human skin models are essential for understanding dermatological diseases and testing new treatment strategies.

Cited by 50 publications

References 38 publications

Skin-on-a-chip models: General overview and future perspectives

Skin-on-a-chip models: General overview and future perspectives

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

Physically Active Bioreactors for Tissue Engineering Applications

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