title: Pumpless microfluidic platform for drug testing on human skin equivalents.
abstract: Advances in bio-mimetic in vitro human skin models increase the efficiency of drug screening studies. In this study, we designed and developed a microfluidic platform that allows for long-term maintenance of full thickness human skin equivalents (HSE) which are comprised of both the epidermal and dermal compartments. The design is based on the physiologically relevant blood residence times in human skin tissue and allows for the establishment of an air-epidermal interface which is crucial for maturation and terminal differentiation of HSEs. The small scale of the design reduces the amount of culture medium and the number of cells required by 36 fold compared to conventional transwell cultures. Our HSE-on-a-chip platform has the capability to recirculate the medium at desired flow rates without the need for pump or external tube connections. We demonstrate that the platform can be used to maintain HSEs for three weeks with proliferating keratinocytes similar to conventional HSE cultures. Immunohistochemistry analyses show that the differentiation and localization of keratinocytes was successfully achieved, establishing all sub-layers of the epidermis after one week. Basal keratinocytes located at the epidermal-dermal interface remain in a proliferative state for three weeks. We use a transdermal transport model to show that the skin barrier function is maintained for three weeks. We also validate the capability of the HSE-on-a-chip platform to be used for drug testing purposes by examining the toxic effects of doxorubucin on skin cells and structure. Overall, the HSE-on-a-chip is a user-friendly and cost-effective in vitro platform for drug testing of candidate molecules for skin disorders.
authors.affiliation: Department of Biomedical Engineering, Cornell University, 115 Weill Hall, Ithaca, New York, USA. mls50@cornell.edu.
authors.forename: Hasan Erbil
authors.initials: HE
authors.lastname: Abaci
authors.forename: Karl
authors.initials: K
authors.lastname: Gledhill
authors.forename: Zongyou
authors.initials: Z
authors.lastname: Guo
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
authors.forename: Michael L
authors.initials: ML
authors.lastname: Shuler
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D052816:Foreskin / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin