Microfluidic skin chip with vasculature for recapitulating the immune response of the skin tissue

Abstract

There is a considerable need for cell‐based in vitro skin models for studying dermatological diseases and testing cosmetic products, but current in vitro skin models lack physiological relevance compared to human skin tissue. For example, many dermatological disorders involve complex immune responses, but current skin models are not capable of recapitulating the phenomena. Previously, we reported development of a microfluidic skin chip with a vessel structure and vascular endothelial cells. In this study, we cocultured dermal fibroblasts and keratinocytes with vascular endothelial cells, human umbilical vascular endothelial cells. We verified the formation of a vascular endothelium in the presence of the dermis and epidermis layers by examining the expression of tissue‐specific markers. As the vascular endothelium plays a critical role in the migration of leukocytes to inflammation sites, we incorporated leukocytes in the circulating media and attempted to mimic the migration of neutrophils in response to external stimuli. Increased secretion of cytokines and migration of neutrophils was observed when the skin chip was exposed to ultraviolet irradiation, showing that the microfluidic skin chip may be useful for studying the immune response of the human tissue.

Evolution of Biochip Technology: A Review from Lab-on-a-Chip to Organ-on-a-Chip

“…Metabolic parameters and change of skin tissue over time have been monitored in this platform. Recently, Kwak et al [133] fabricated a skin-on-a-chip microfluidic platform in which epidermal and dermal layers were co-cultured with human umbilical vascular endothelial cells. Immune responses such as an increase in secretion of cytokines and migration of neutrophils into the demal layer after exposure to doxorubicin and UV irradiation have been observed.…”

Microphysiological Systems for Studying Cellular Crosstalk During the Neutrophil Response to Infection

“…These studies showed synovial fibroblasts from patients with rheumatoid arthritis increased the number of neutrophils adhering to endothelial cells compared to their healthy counterparts. Recently, a device incorporating a flat endothelium, fibroblasts in a sub-luminal collagen gel, and a keratinocyte monolayer was developed (139). Using this model, Kwak et al demonstrated ultraviolet lightinduced cytokine secretion by the resident cells increased neutrophil TEM.…”

Microphysiological systems: What it takes for community adoption

“…12 A useful prioritization of MPS applications can be found in Table 1 of the review by Watson, Hunziker, and Wikswo, 2017. 10 Currently, there are MPS of nearly every major human organ 20 including liver, 16,41 vasculature, 42,43 blood-brain barrier (BBB), [44][45][46] skeletal [47][48][49] and cardiac muscle, [50][51][52][53][54][55][56][57] kidney, [58][59][60][61] female reproductive tissues (uterus, cervix, fallopian tubes), 62 testes, 63 brain, 37,64 skin, [65][66][67] gut, 40 bone, 68 and eye. 69,70 Specific MPS organ systems have also been linked to form multi-organ systems to more accurately depict systemic responses to a variety of drugs and therapeutics.…”