An advanced microfluidic platform to study cellular responses in 3D microenvironments
Cell migration is essential for a variety of physiological and pathological processes, such as angiogenesis, cancer metastasis, wound healing and inflammation. In the vascular system, significant efforts have focused on cell migration in the context of capillary morphogenesis. Through these studies, various mechanical and biochemical factors have been identified as critical in regulating endothelial cell migration and tube formation, such as chemotactic or chemo-kinetic effects of single and/or multiple growth factors, interstitial fluid flow and matrix stiffness. Despite the detailed understanding of individual components, how these factors are integrated to produce a specific cellular response has to be elucidated, This creates the need for a versatile in vitro system in which these factors can be studied in a controlled fashion. The aim is to facilitate investigations that lead to a better understanding of how biochemical and mechanical factors act together in physiological and patho-physiological processes and ultimately contribute to improved tissue engineering and therapeutic strategies.
We have developed a 3D microfluidic system by integrating a hydrogel scaffold into a PDMS device for cell growth, with co-culture capability. The devices contain three independent flow channels with each channel separated by a 3D collagen scaffold filled through other microchannels. We have studied endothelial cell migration into collagen scaffolds under a gradient growth factor and also under various co-culture conditions. Details have been published in Lab Chip, 9, 269–275 (2009).
This novel microfluidic platform has proven to be a versatile and powerful tool to study cell migration for various biological applications. It provides a well-controlled cell culture environment which can be observed in real time. Furthermore, it allows for an integration of biophysical and biochemical factors, essential in mimicking physiological conditions as cells constantly receive signals from both their soluble and insoluble environments. We are now exploring new applications with this platform as a model system for physiological and pathophysiological phenomena such as angiogenesis, arteriogenesis, stem cell differentiation, cancer intravasation and extravasation.