Bachmann, B. | bioRxiv Science

bioRxiv2022

The p-rpS6-zone delineates wounding response and the healing process

It is unknown what the spatial boundaries of tissue response to wounding are. Here we show that in mammals the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is complete. The zone encapsulates markers of the healing process, including proliferation, senescence, and angiogenesis in wounded skin. A mouse model unable to phosphorylate rpS6 shows an initial acceleration of wound closure, but results in disrupted healing. Finally, the p-rpS6-zone accurately reports on the status of dermal vasculature and the effectiveness of healing. In summary, the zone divides an otherwise homogenous tissue into regions with distinct properties.

physiology↗

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↗