Recent Advances in Additive Manufacturing and 3D Bioprinting for Organs-On-A-Chip and Microphysiological Systems.

The re-creation of physiological cellular microenvironments that truly resemble complex in vivo architectures is the key aspect in the development of advanced in vitro organotypic tissue constructs. Among others, organ-on-a-chip technology has been increasingly used in recent years to create improved models for organs and tissues in human health and disease, because of its ability to provide spatio-temporal control over soluble cues, biophysical signals and biomechanical forces necessary to maintain proper organotypic functions. While media supply and waste removal are controlled by microfluidic channel by a network the formation of tissue-like architectures in designated micro-structured hydrogel compartments is commonly achieved by cellular self-assembly and intrinsic biological reorganization mechanisms. The recent combination of organ-on-a-chip technology with three-dimensional (3D) bioprinting and additive manufacturing techniques allows for an unprecedented control over tissue structures with the ability to also generate anisotropic constructs as often seen in in vivo tissue architectures. This review highlights progress made in bioprinting applications for organ-on-a-chip technology, and discusses synergies and limitations between organ-on-a-chip technology and 3D bioprinting in the creation of next generation biomimetic in vitro tissue models.

A Decade of Organs-on-a-Chip Emulating Human Physiology at the Microscale: A Critical Status Report on Progress in Toxicology and Pharmacology.

Organ-on-a-chip technology has the potential to accelerate pharmaceutical drug development, improve the clinical translation of basic research, and provide personalized intervention strategies. In the last decade, big pharma has engaged in many academic research cooperations to develop organ-on-a-chip systems for future drug discoveries. Although most organ-on-a-chip systems present proof-of-concept studies, miniaturized organ systems still need to demonstrate translational relevance and predictive power in clinical and pharmaceutical settings. This review explores whether microfluidic technology succeeded in paving the way for developing physiologically relevant human in vitro models for pharmacology and toxicology in biomedical research within the last decade. Individual organ-on-a-chip systems are discussed, focusing on relevant applications and highlighting their ability to tackle current challenges in pharmacological research.

Monitoring tissue-level remodelling during inflammatory arthritis using a three-dimensional synovium-on-a-chip with non-invasive light scattering biosensing.

Rheumatoid arthritis is a chronic, systemic joint disease in which an autoimmune response translates into an inflammatory attack resulting in joint damage, disability and decreased quality of life. Despite recent introduction of therapeutic agents such as anti-TNFα, even the best current therapies fail to achieve disease remission in most arthritis patients. Therefore, research into the mechanisms governing the destructive inflammatory process in rheumatoid arthritis is of great importance and may reveal novel strategies for the therapeutic interventions. To gain deeper insight into its pathogensis, we have developed for the first time a three-dimensional synovium-on-a-chip system in order to monitor the onset and progression of inflammatory synovial tissue responses. In our study, patient-derived primary synovial organoids are cultivated on a single chip platform containing embedded organic-photodetector arrays for over a week in the absence and presence of tumor-necrosis-factor. Using a label-free and non-invasive optical light-scatter biosensing strategy inflammation-induced 3D tissue-level architectural changes were already detected after two days. We demonstrate that the integration of complex human synovial organ cultures in a lab-on-a-chip provides reproducible and reliable information on how systemic stress factors affect synovial tissue architectures.

Optimized plasma-assisted bi-layer photoresist fabrication protocol for high resolution microfabrication of thin-film metal electrodes on porous polymer membranes.

Structured metal thin-film electrodes are heavily used in electrochemical assays to detect a range of analytes including toxins, biomarkers, biological contaminants and cell cultures using amperometric, voltammetric and impedance-based (bio)sensing strategies as well as separation techniques such as dielectrophoresis. Over the last decade, thin-film electrodes have been fabricated onto various durable and flexible substrates including glass, silicon and polymers. However, the combination of thin-film technology with porous polymeric substrates frequently used for biochips often results in limited resolution and poor adhesion of the metal thin-film, thus severely restricting reproducible fabrication and reliable application in e.g. organ-on-a-chip systems. To overcome common problems associated with micro-structured electrode manufacturing on porous substrates, we have optimized a bi-layer lift-off method for the fabrication of thin-film electrodes on commercial porous polyester membranes using a combination of LOR3A with AZ5214E photoresists. To demonstrate practical application of our porous electrode membranes for trans-epithelial electrical resistance measurements a tetrapolar biosensing set-up was used to eliminate the artificial resistance of the porous polymer membrane from the electrochemical recordings. Furthermore, barrier resistance of Bewo trophoblast epithelial cells was compared to a standard Transwell assay readout using a EVOM2 volt-ohm meter. •Bi-layer photo resist lift-off yields resolution down to 2.5 µm.•Argon Plasma-assisted lift-off results in improved adhesion of gold thin films and eliminates the need for chromium adhesion layers.•Membrane electrodes can be used for elimination of the porous membrane resistance during tetra-polar epithelial resistance measurements.