Wanzenboeck, H. D. | bioRxiv Science

bioRxiv2022

Development of a multi-sensor integrated midbrain organoid-on-a-chip platform for studying Parkinson's disease

Due to its ability to recapitulate key pathological processes in vitro, midbrain organoid technology has significantly advanced the modeling of Parkinsons disease over the last few years. However, some limitations such as insufficient tissue differentiation and maturation, deficient nutrient supply, and low analytical accessibility persist, altogether restricting the technology from reaching its full potential. To overcome these drawbacks, we have developed a multi-sensor integrated organ-on-a-chip platform capable of monitoring the electrophysiological, respiratory, and dopaminergic activity of human midbrain organoids. Our study showed that microfluidic cultivation resulted in a marked reduction in necrotic core formation, improved tissue differentiation as well as the recapitulation of key pathological hallmarks. Non-invasive monitoring employing an orthogonal sensing strategy revealed a clear time dependency in the onset of Parkinsons disease-related phenotypes, reflecting the complex progression of the neurodegenerative disorder. Furthermore, drug-mediated rescue effects were observed after treatment with the repurposed compound 2-hydroxypropyl {beta}-cyclodextrin, highlighting the platforms potential in the context of drug screening applications as well as personalized medicine.

bioengineering↗

bioRxiv2021

Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

After decades of simply being referred to as the bodys sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulations importance on lymphatic sprout formation. Our microvascular models key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

bioengineering↗