Table of contents

Understanding complex cell–cell interactions and physiological microenvironments is critical for the development of new therapies for treating human diseases. Current animal models fail to accurately predict success of therapeutic compounds and clinical treatments. Advances in biomaterials, engineering, and additive manufacturing have led to the development of printed tissues, lab-on-chip devices, and, more recently, organ-on-chip systems. These technologies have promising applications for the fabrication of more physiologically representative human tissues and can be used for high-throughput testing of human cells and organoids. These organ-on-chip systems can be fabricated with integrated fluidics to allow for the precise control and manipulation of cellular microenvironments with multiple cell types. Further control over these cellular environments can be achieved with bioprinting, allowing for three-dimensional (3D) printing of multiple materials and cell types to provide precisely controlled structures manufactured in a one-step process. As cell behavior is highly dependent on the physical and chemical properties of the environment, the behavior of cells in two-dimensional and 3D culture systems varies drastically. Providing devices that can support long-term cell culture and controlled stimulation of 3D culture systems will have a profound impact on the study of physiological processes and disease, as well as the development of new therapies. This review highlights recent advances in organ-on-chip systems and 3D bioprinting techniques for the development of in vitro physiological models.

Untethered mobile microrobots have the potential to transform medicine radically. Their small size and wireless mobility can enable access to and navigation in confined, small, hard-to-reach, and sensitive inner body sites, where they can provide new ways of minimally invasive interventions and targeted diagnosis and therapy down to the cellular length scales with high precision and repeatability. The exponential recent progress of the field at the preclinical level raises anticipations for their near-future clinical prospects. To pave the way for this transformation to happen, however, the formerly proposed microrobotic system designs need a comprehensive review by including essential aspects that a microrobot needs to function properly and safely in given in vivo conditions of a targeted medical problem. The present review provides a translational perspective on medical microrobotics research with an application-oriented, integrative design approach. The blueprint of a medical microrobot needs to take account of microrobot shape, material composition, manufacturing technique, permeation of biological barriers, deployment strategy, actuation and control methods, medical imaging modality, and the execution of the prescribed medical tasks altogether at the same time. The incorporation of functional information pertaining each such element to the physical design of the microrobot is highly dependent on the specific clinical application scenario. We discuss the complexity of the challenges ahead and the potential directions to overcome them. We also throw light on the potential regulatory aspects of medical microrobots toward their bench-to-bedside translation. Such a multifaceted undertaking entails multidisciplinary involvement of engineers, materials scientists, biologists and medical doctors, and bringing their focus on specific medical problems where microrobots could make a disruptive or radical impact.

Large population-based studies have helped to identify cardiovascular risk factors and to understand the natural progression of diseases. Cardiac magnetic resonance (CMR) is the reference method for the assessment of ventricular morphology and function given the low variance between scans. In addition, advanced sequences such as MR tagging, T1 mapping, and late gadolinium enhancement allow to assess regional ventricular function and fibrotic changes. MESA was the first study to use CMR on a large scale in a sample of the general population. Subsequent studies focused on cohorts of particular ethnicities or from certain locations with the Jackson Heart Study looking at African-Americans and the Dallas Heart Study at Dallas County Residents. More recently, the German National Cohort and UK Biobank have started to perform CMRs in a significantly larger number of participants (30 000 and 100 000, respectively). The introduction of CMR into prospective cohort studies has allowed to characterize ventricular remodeling in individuals of different age, sex, and gender and has found associations with new environmental exposures. The ability to detect subclinical changes in asymptomatic individuals has also been highlighted by reports of a high number of missed myocardial infarctions (MI) using CMR. In this review, we discuss the use of CMR in the different large population-based studies and compare the various associations found with left and right ventricular structure and function. In addition, we outline automated image analysis strategies aimed at overcoming challenges posed by the large amount of data in population-based studies.

At the present time, there is a significant public and political debate about the safety of implantable medical devices. The debate has centered on the biocompatibility of materials that are used in such devices. It has become clear that, whether the concerns expressed about adverse events in patients are actually caused by the devices or just coincidentally arise in these patients, we are usually unable to address and explain the phenomena that are described. This is very damaging to the medical device industry and the relevant clinical disciplines; it is, however, not surprising, since current ideas about the mechanisms of biocompatibility and the development of the host response are well out-of-date and do not take into account knowledge about inflammation, immunity and fibrosis. This perspectives paper discusses this new knowledge and presents the outline of new biocompatibility paradigms, involving mechanotransduction and sterile inflammation. Based on these ideas, totally new procedures for the determination of biological safety are proposed which, if implemented, could improve patient safety and confidence in the performance of implanted devices.