Exploring microfluidics as a tool to study cell-biomaterial interactions

Sammanfattning: Considering the tremendous amount of research on the development of novel biomaterials, relatively few of these have reached the patient. This can at least in part be explained by the lack of predictive power of the currently used in vitro models, which are nowadays recognized to be too reductionist to accurately predict in vivo complexity. Recently, microfluidics-based (i.e. on-chip) systems have been proposed as a promising method to enhance physiological relevance in an in vitro environment. A key feature of such a system is that it contains one or multiple channels, with at least one dimension at the micrometer scale. Such channels enable cell confinement at more physiologically relevant length scales and a higher level of control over the microenvironment. In addition to this, there is the option to provide fluid flow, which does not only provide nutrients to and remove waste from the cells, but can also mechanically stimulate the cells. The aim of this thesis was to explore microfluidics as a tool to evaluate cell-biomaterial interactions, particularly in the context of bone tissue. Two main themes can be distinguished, namely the characterization of microfluidics-based systems in general and the integration of biomaterials on-chip. First, the effect of one of the most commonly used materials to fabricate microfluidic systems, namely polydimethylsiloxane, and different flow types (i.e. unidirectional or recirculation) on the behavior of cells were evaluated. Afterwards, different approaches to integrate clinically relevant biomaterials, namely medical-grade titanium and calcium-deficient hydroxyapatite, were described and used to characterize these biomaterials under flow. Overall, the work presented in this thesis demonstrates that it is possible to use a microfluidics-based method to evaluate biomaterials. It was also shown that cells respond differently when maintained under static conditions or on-chip, illustrating the importance of optimizing the in vitro cell culture environment. Lastly, it was illustrated that the differences between a conventional static well plate and a microfluidic system go much beyond static versus dynamic conditions and that factors such as the material properties and the type of flow should be carefully considered in order to make conclusive statements regarding cell behavior and performance of the systems.