Engineered infected epidermis model for in vitro study of the skin proinflammatory response

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dc.contributor.authorJahanshahi, Maryam
dc.contributor.supervisorAkbari, Mohsen
dc.date.accessioned2020-01-24T22:41:34Z
dc.date.available2020-01-24T22:41:34Z
dc.date.copyright2020en_US
dc.date.issued2020-01-24
dc.degree.departmentDepartment of Mechanical Engineeringen_US
dc.degree.levelMaster of Applied Science M.A.Sc.en_US
dc.description.abstractWound infection is a major clinical burden that can significantly impede the healing process and cause severe pain. Prolonged wound infection can lead to long-term hospitalization or death. Pre-clinical research to evaluate new drugs or treatment strategies relies on animal studies. However, animal studies have several challenges including interspecies variations, cost, and, ethics question the success of these models. Recent advances in tissue engineering have enabled the development of in vitro human skin models for wound infection modeling and drug testing. The existing skin models are mostly representative of the healthy human skin and its normal functions. However, to study the wound healing process and the response of skin to the infection, there is still a need to develop a skin model mimicking the wound infection. This work presents a simplified functional infected epidermis model, fabricated with enzymatically crosslinked gelatin hydrogel. The immortalized human keratinocytes, HaCaT cells, was successfully cultured and differentiated to a multilayer epidermis structure at the air-liquid interface, and expressed terminal differentiation marker, filaggrin, in the outer layer. The barrier function of the epidermis model was studied by measuring the electrical resistance and tissue permeability across the layer. The results showed that the developed epidermis model offered a higher electrical resistance and a lower drug permeability compared to the cell monolayer on gelatin and cell-free gelatin. To show the capability of the developed epidermis model in wound modeling and drug, the model was infected with Escherichia coli and the inflammatory response of keratinocytes was studied by measuring the level of proinflammatory cytokines, including IL-1β and TNF-α. The results demonstrated the proinflammatory response of the epidermis model to infection by producing a higher level of TNF-α and IL-1β compared to the control group. While treating with antibiotic ciprofloxacin terminated the proinflammatory response and reduced the level of TNF-α and IL-1β. The robust fabrication procedure and functionality of this model suggest that this model has great potential for wound modeling and high throughput drug testing.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.urihttp://hdl.handle.net/1828/11507
dc.languageEnglisheng
dc.language.isoenen_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectepidermis modelen_US
dc.subjectinfected epidermis modelen_US
dc.subjectskin inflammatory responseen_US
dc.subjectgelatin-based skin modelen_US
dc.subjectinfected wound modelingen_US
dc.subjectwound infectionen_US
dc.subjecttissue engineered skin modelen_US
dc.titleEngineered infected epidermis model for in vitro study of the skin proinflammatory responseen_US
dc.typeThesisen_US

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