Microfluidic devices for studies of cell behavior
Conventional biomedical research methods are restrained to 2D static cell cultures and animal testing, both of them falling short as preclinical models. In this context, there is a dire need for reliable biomimetic systems, able to minimize the mismatches of the traditional methods. Cutting edge techniques from the field of microelectronics being applied in microfluidics technology and the development of Lab-on-a-chip devices, paved the way to Organs-on-chips (OoCs). These novel 3D microfluidic cell culture devices lined with living cells, are considered the epitome of biomimetic systems, being able to faithfully recapitulate the physiology and function of a vital human organ unit.
Focusing on the subject of study, bone marrow-on-a-chip (BMoC) systems, current studies are confined to mere in vitro maintenance of the hematopoietic organoid, which is supported with 3D scaffolds, let them be gels or embodied artificial matrices. In this project, we introduce a purely in vitro and scaffold-free bone marrow-on-a-chip device, intended for both the generation and sustainment of the perivascular hematopoietic niche, capable to reproduce the mechanism of haematopoiesis, for an approximate time period of one week. Afterwards, the device is intended to be used as a study platform for the chronic autoimmune disease of Systemic Lupus Erythematosus (SLE), in cooperation with researchers from the Biomedical Research Foundation Academy of Athens (BRFAA).
In detail, the proposed device consists of three layers of poly(dimethylsiloxane) (PDMS), including two cylindrical microchambers separated by an intervening porous membrane, altogether bonded to a glass slide. The device has been successfully constructed, while static culture experiments have been performed in cell culture microchambers as early-stage platforms for the on-chip application. These experiments proved the ability to purely in vitro create and preserve 3D bone marrow stromal tissue in microchambers, a promising outcome for subsequent testing on the platform.
As a means of device optimization, a new architecture is introduced, based on the concept of static cell culture, in order to avoid bubble generation. According to the new design, the medium microchamber will be open and sunk in the medium reservoir, which will be daily renewed. The two platforms, the initial of continuous perfusion and the new of static culture, are to be compared regarding their capacity to sustain the bone marrow organoid.