New complex, bone layer incorporating human in vitro skin model for testing of non-invasive glucose sensors

In this project, we will use advanced biomedical engineering methods (e.g. 3D bio-printing and core/shell printing) to create a new in vitro model of human skin that will simulate all important skin layers in their full physiological complexity. It will provide a reliable platform for various functional in vitro testing methods (e.g., efficiency testing of non-invasive sensors, testing of pharmaceutical and cosmetic products, etc.). Since the development of non-invasive sensors is growing and they require a reflective surface to function (in the case of skin, this is the bone), we will additionally include an in vitro bone layer on medical steel underneath the skin model to ensure that non-invasive sensors can be effectively tested. The specially designed skin layers will include: i) an epidermal layer with keratinocytes, ii) a dermal layer with fibroblasts, iii) a subdermal layer with adipocytes, iv) a bone layer made from a metal substrate and osteoblasts, v) and a circulatory system of artificial vessels made with endothelial cells. The latter will be enabled by an integrated pump system that can simulate blood circulation in the skin. All layers will resemble the integrity of the skin not only by the incorporated cells and mimicking the structural (3D architecture) and (bio)chemical (by using native extracellular matrix components or similar chemical constituents) properties of the respective tissues/layers, but also by the functional properties of the simulated tissues (e.g., blood circulation through the circulatory system, which allows mimicing the physiological/pathophysiological flow in the vessels). Such a complex skin model will serve as a representative in vitro testing platform, comparable to the in vivo environment, in/on/at which different in vitro testing methods could be performed and/or newly developed. Such a complex in vitro skin model will allow comparable in vitro testing to in vivo testing on/through/in the skin. The idea for the development of the system came from a collaboration with a company developing a non-invasive sensor for glucose measurement, so we additionally included the development of an in vitro bone layer. Given the magnitude of the diabetes epidemic, such a sensor, which will also be used as a proof-of-principle “testing device” as part of the project, represents an important step forward in addressing a pressing public health issue. Figure 1 shows a general overview of the proposed project.