species and tissue Specific extracellular Matrix produced by mesenchymal stem cells for Representative in vitro models and Tissue Engineering

The extracellular matrix (ECM) is a highly organized tissue-specific network, which is secreted by tissue-resident cells and significantly influences cell phenotype, behaviour and function. The 3R principle calls for the replacement of animal models in areas like drug screening, and consequently, numerous 3D in vitro models are being developed. A key element, however, is providing an adequate, controlled environment for cell expansion and differentiation by dynamically displaying appropriate mechanical properties and the correct biochemical and biophysical cues, similar to the ECM in vivo. Additionally, in regenerative medicine, tissue engineering (TE) strategies are used to restore the physiological architecture and biomechanical function after injury. In this project, cell-derived ECM is being used as an alternative to the commonly used, but badly defined, murine tumor-derived matrices, such as Matrigel and Geltrex. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that reside in nearly all tissues and organs and play an important role in tissue homeostasis. After isolating MSCs form various tissues, a species- and tissue-specific matrix can be harvested to represent the (patho-) physiological microenvironment. Using chemical modification, the mechanical properties of the ECM-based biomaterial can be tuned towards various applications, ranging from adipose and skin TE to intestinal organoid models. Additionally, the biomaterial will be processable using various additive manufacturing techniques, such as 3D extrusion printing, light-based printing (DLP, SLA) and volumetric printing to further improve biomimicry of the models. The development of these species- and tissue-specific biomaterials will further enhance the design of reliable in vitro models and improve the outcomes of regenerative medicine.