The development of a dynamically perfused system for models of the human airways, with automated feeding and sampling capability

The development of relevant in vitro models to replace outdated animal models is the focus of many life science researchers. Whilst the cellular make-up of models can be made physiologically relevant, often the delivery of nutrients to, and the collection of samples from, these models can be static and un-realistic. Combining biological expertise with engineering know-how has allowed our team to focus on the development of a dynamically perfused cell culture environment which aims to enable relevant biological functionality. There are currently no perfusion models of the upper airways, despite recent evidence recognising the role of small airways in human chronic respiratory disease. This project has three specific objectives. 1) design and build a perfused system, 2) identify the optimum flow parameters, and 3) design and build a sampling system. This is an ongoing project, enabled through the Dr Hadwen Trust Summer Studentship Scheme, and here we present the first phase of development including the prototyping of cell chambers and manifolds using 3D printing and careful materials selection processes, the advancement of programmable systems for timed sampling to meet individual user requirements and the development of prototyped automated apparatus for sample collection. Future work will combine the engineering aspects with the biological side and begin to analyse the effects perfusion will have on cell viability and the effects of introducing challenges to measure cytotoxicity. If successful, this project could provide an alternative to highly severe experiments involving dogs and rodents where airways are challenged through direct exposure or chemical damage.