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In recent years, innovative cell-based biosensing systems have been developed, showing impact in healthcare and life science research. Now, there is a need to design mass-production processes to enable their commercialization and reach society. However, current protocols for their fabrication employ materials that are not optimal for industrial production, and their preparation requires several chemical coating steps, resulting in cumbersome protocols. We have developed a simplified two-step method for generating controlled cell patterns on PMMA, a durable and transparent material frequently employed in the mass manufacturing of microfluidic devices. It involves air plasma and microcontact printing. This approach allows the formation of well-defined cell arrays on PMMA without the need for blocking agents to define the patterns. Patterns of various adherent cell types in dozens of individual cell cultures, allowing the regulation of cell–material and cell–cell interactions, were developed. These cell patterns were integrated into a microfluidic device, and their viability for more than 20 h under controlled flow conditions was demonstrated. This work demonstrated the potential to adapt polymeric cytophobic materials to simple fabrication protocols of cell-based microsystems, leveraging the possibilities for commercialization.

Cardiovascular disease morbidity has increased worldwide. Organs-on-chips and human pluripotent stem cell (hPSC) technologies aid to overcome some of the limitations in cardiac in vitro models. Here, a bi-compartmental, monolithic heart-on-chip device that facilitates porous membrane integration in a single fabrication step is presented. Moreover, the device includes open-top compartments that allow facile co-culture of hPSC-derived cardiomyocytes and human adult cardiac fibroblast into geometrically defined cardiac microtissues. The device can be reversibly closed with a glass seal or a lid with fully customized 3D-printed pyrolytic carbon electrodes allowing electrical stimulation of cardiac microtissues. A subjacent microfluidic channel allowed localized and dynamic drug administration to the cardiac microtissues, as demonstrated by a chronotropic response to isoprenaline. Moreover, the microfluidic channel can also be populated with human induced pluripotent stem-derived endothelial cells allowing co-culture of heterotypic cardiac cells in one device. Overall, this study demonstrates a novel heart-on-chip model that systematically integrates an open-top device with a 3D printed carbon electrode for electrical pacing and culture of cardiac tissues while enabling active perfusion and dynamic drug dosing. Advances in the engineering of human heart-on-chip models represent an important step towards making organ-on-a-chip technology a routine aspect of preclinical cardiac drug development.

The development of organs-on-chip (OoC) has revolutionized in vitro cell-culture experiments by allowing a better mimicry of human physiology and pathophysiology that has consequently led researchers to gain more meaningful insights into disease mechanisms. Several models of hearts-on-chips and vessels-on-chips have been demonstrated to recapitulate fundamental aspects of the human cardiovascular system in the recent past. These 2D and 3D systems include synchronized beating cardiomyocytes in hearts-on-chips and vessels-on-chips with layer-based structures and the inclusion of physiological and pathological shear stress conditions. The opportunities to discover novel targets and to perform drug testing with chip-based platforms have substantially enhanced, thanks to the utilization of patient-derived cells and precise control of their microenvironment. These organ models will provide an important asset for future approaches to personalized cardiovascular medicine and improved patient care. However, certain technical and biological challenges remain, making the global utilization of OoCs to tackle unanswered questions in cardiovascular science still rather challenging. This review article aims to introduce and summarize published work on hearts- and vessels-on chips but also to provide an outlook and perspective on how these advanced in vitro systems can be used to tailor disease models with patient-specific characteristics., De tre sista författarna delar sistaförfattarskapet

For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). To increase the regulatory use and acceptance of NAMs for biokinetics for these ADME considerations within risk evaluations, the development of test guidelines (protocols) and of overarching guidance documents is considered as a critical step. To this end, a need for an expert group on biokinetics within the Organisation of Economic Cooperation and Development (OECD) was formulated to supervise this process. The workshop discussions revealed that method development is still required, particularly to adequately capture transporter mediated processes as well as to obtain cell models that reflect the physiology and kinetic characteristics of relevant organs. Developments in the field of stem-cells, organoids and organ-on-a-chip provide promising tools to meet these research needs in the future.