Abstract

Development of Skin-on-Chip Containing Neopapillae and Proof-of-Concept Hazard Assessment Testing with Contact Sensitizer Cinnamaldehyde

Irit Vahav, PhD student, VUmc

Contact with the skin is inevitable for daily life products. The major penetration routes for these substances are via the hair shaft and stratum corneum. Therefore skin models which closely represent skin physiology and which incorporate the skin penetration routes are required for hazard assessment. Aim: to develop human skin-on-chip containing neopapillae and establish Proof-of-Concept testing with contact sensitizer cinnamaldehyde. Dermal papilla cells were isolated from human hair follicles, expanded and used to reconstruct neopapillae. Neopapilla were incorporated into a bilayered skin substitute (reconstructed epidermis on a fibroblast populated hydrogel). The air lifted construct was further cultured for at least 10 days in the TissUse bioreactor. Cinnamaldehyde was applied topically and viability and cytokine secretion assessed over 7 days. The skin-on-chip containing neopapillea was viable for 10 days under dynamic flow within the bioreactor. Topical administration of cinnamaldehyde to the stratum corneum resulted in dose dependent cytotoxicity (release of LDH) and cytokine IL-18 release into the microfluidic culture medium. Proof of concept testing of skin-on-chip containing neopapillae with cinnamaldehyde demonstrates the next generation of skin models under development for investigating local and systemic toxicity to chemicals.