Work on all sub-aims has been completed and has led to successful results in line with the proposed action. The key achievements in the sub-aims are listed below:
We achieved differentiation of endothelial cells from hiPSC, as well as their long-term culture inside microfluidic culture systems (sub-aim 1). We developed a modular, automated microfluidic cell culture platform, and demonstrated its use in long-term culture of vascular tissues (sub-aim 2). We demonstrated the formation of microvascular networks in microfluidic chips with a superior degree of control due to the microfluidic patterning of hydrogels (sub-aim 3). We developed electrical sensors for pH and used them to track the metabolic activity of human stem cell-derived tissues (sub-aim 4). We systematically studied the formation of blood clots in 3D-printed microfluidic cultures ('vessels-on-chips') and demonstrated that hiPSC-derived cells are capable of inducing platelet aggregation and fibrin formation in vitro (sub-aim 5). And finally, we studied how human brain microvascular endothelial cells can be cultured in microfluidic chips, and how this affects their barrier function when compared to conventional culture systems (sub-aim 6).
This substantial scientific progress has led to multiple publications (see 'Publications' in report) in scientific journals, as well as accepted abstracts for major conferences in the field (e.g. microTAS, NanoBioTech, International Organ-on-Chip Sympsosium, Micro and Nanotechnology in Medicine Conference, European Organ-on-Chip Society Annual Meeting).
The development of the modular automated microfluidic culture platform in sub-aim 2 was used as a basis for applying for an ERC Proof-of-Concept funding. This funding was granted, and the platform is now being further developed for use in the field of organs-on-chips as an 'open platform' that can control multiple microfluidic chips via a standardized interface.
