Organ-on-a-chip

Great advances have been made on the engineering of vascular networks in Organs-on-Chips (OoC). However, the integration of a vascular network within an OoC with high-density 3D tissue remains a challenge. In this work we demonstrate a vascularized heart-on-chip through the step-wise encapsulation of preformed cardiac tissues in a bioactive hydrogel loaded with endothelial cells.

We use a polydimethylsiloxane (PDMS)-based chip which has three parallel channels separated by phaseguides. The central channel has two pillars that are used to anchor a micro-engineered heart tissue (μEHT). The μEHT consists of iPSC-derived cardiomyocytes and adult human cardiac fibroblasts. The cells are seeded in a Matrigel-fibrin mix, which contracts to form a μEHT. The tissue is fully formed and spontaneously beating after 4 days. Then, the tissue and the surrounding PDMS walls are coated with polydopamine to enable the attachment of the fibrin hydrogel to the PDMS, after which a fibrin hydrogel loaded with iPSC derived endothelial  cells (ECs) and smooth muscle cells (SMCs) is injected around the μEHTS. The following days the vasculogenesis of the ECs in the hydrogel can be observed.

After encapsulation of the μEHT with the EC-loaded hydrogel, migration of fibroblasts originating from the μEHT into the hydrogel is observed, as well as migration of ECs from the hydrogel into the μEHT further confirming the attachment of the hydrogel with the μEHT. Early degradation of the endothelial network was prevented through the addition of SMCs in the hydrogel, resulting in an endothelial network that remained stable for at least 7 days

 In conclusion, we show the formation of vascular networks in a bioactive hydrogel surrounding a μEHT in a heart-on-chip and migration of the endothelial cells into the μEHT itself.

In this work, we report a standardized, modular, and reconfigurable translational organ-on-chip platform. We demonstrate a fluidic circuit board that combines multiple organ-on-chip devices with modules for pumping and in-line sensing, all within the footprint of a multi-well plate. The modularity is utilized to add a ‘routing block’ that can configure all the circuits on the platform, thus enabling parallel or combined perfusion of the OoC devices. Functionalities like mixing and dosing are shown as additional possibilities with the routing and pumping blocks. The system is designed to be standalone and compatible with standard imaging setups to improve ease of adoption.

The generic Multi-OoC platform is designed adhering to ISO 22916, facilitating interfacing with modules designed according to the same international standards. We demonstrate the integration of commercial and custom modules while implementing ISO design rules on a variety of OoC designs to showcase versatility, ease of design, and interoperability. In an additional example of ISO-driven collaboration, a specific platform is designed to interface with OoC modules designed by researchers from Tampere University. Thus also showcasing the potential of the design guidelines for customized applications such as, automation and integration of specialized experiments, chips and sensors. Furthermore, the designs are documented in an open-source library. These resources are envisioned to help guide or initiate designing of ISO-compatible modules in the community.

Fibrosis is a condition associated with multiple diseases, characterized by an over-accumulation of fibrous connective tissue in inflamed or damaged areas, ultimately leading to organ failure. The condition is driven by the activation of fibroblasts and their differentiation into myofibroblasts, which is accompanied by an over-expression of cytokines and growth factors (e.g., TGF-β, TNF-α, IL-1, and IL-6), and abnormal remodeling of the microenvironment, leading to hypoxia and vasculopathy. There are no good models of fibrotic diseases due to essential cellular and molecular inter-species differences and/or the lack of a relevant three-dimensional microenvironment, including mechanical factors and hypoxia, while such models are essential for developing treatment strategies.

Here, we are developing a humanized in-vitro fibrotic disease model, focusing on systemic sclerosis (SSc), a characteristic disease affecting the skin, by incorporating essential physicochemical features of this disease. For this purpose, we first established a healthy vascular unit in a PDMS-based microfluidic platform by optimizing microenvironmental factors such as extracellular matrix composition, and cellular types. Self-assembled vascular structures were characterized through daily microscopic observations and expression of endothelial marker CD31 and adherens junction protein VE-Cadherin. Afterward, we assessed the impact of fibrosis on new microvasculature formation by daily TGF-β stimulation which is widely used to induce fibrosis.

Current characterization focuses on the perfusability of the newly formed microvasculature under both healthy and fibrotic conditions. In later stage, after the incorporation of hypoxic conditions, stretching-type mechanical stimulation of the tissue and inclusion of patient-derived materials, a fully SSc-on-chip model will be achieved.

Locsense develops and supplies in-vitro sensing equipment for barrier integrity assays.  In-vitro experiments are a promising alternative and addition to  animal testing. Legislation in the EU and USA is driving the need for alternatives. Locsense enables toxicologists and drug developers to improve their predictive models. During this talk the relevance of impedance spectroscopy for different models is explained.

Impedance spectroscopy is a powerful, non-invasive technique that has revolutionized the analysis of cellular cultures. By measuring the electrical impedance across a range of frequencies, researchers can gain insights into the integrity and differentiation of both 2D and 3D in-vitro cultures. This method is particularly valuable for toxicity and efficacy studies in fields such as cosmetic and drug development.