Engineering a bioprinted vascularized 3D in-vitro model to study tumor progression and liver metastasis

In vitro models are becoming increasingly important for gaining a mechanistic understanding of tumor biology and for testing new drugs for tumor therapy. However, established 2D in vitro models cannot adequately represent all pathophysiological properties. This limitation requires their further development into more complex 3D in vitro models consisting of several cell types that better simulate the in vivo situation.

The aim of this project, funded by the German Research Foundation (DFG) and carried out in collaboration with a university partner, is to develop a 3D in vitro model capable of representing the entire hematogenous metastatic process of a breast cancer tumor in the liver. In addition to the development of a tumor and a liver model, their connection via a biofunctional vascular structure is required. In preliminary work, a bioreactor was developed in which the tumor model can be cultivated [1].

In this research project, the synthesis of a liver-like tissue will be optimized and an additional bioreactor for its cultivation will be developed. The liver model will then be connected to the tumor model via a biofunctional vascular structure. The liver model consists of relevant liver cells, which are embedded in a hydrogel mixture adapted to the native extracellular matrix. Various 3D biofabrication techniques are used to create the complex liver architecture and the vascular structures. The design of the bioreactor allows analysis using multiscale and multimodal imaging techniques.

After successful establishment of the novel 3D model, the entire hematogenous metastatic process, consisting of motility of the metastatic tumor cells within the primary tumor, their intravasation into and transport within the vascular system, their survival in the fluid flow, as well as their deposition and spread in the liver-like tissue, can be studied in vitro.

_{[1] Lorenzi F de, Hansen N, Theek B, Daware R, Motta A, Breuel S, Nasehi R, Baumeister J, Schöneberg J, Stojanović N, Stillfried S von, Vogt M, Müller-Newen G, Maurer J, Sofias AM, Lammers T*, Fischer H*, Kiessling F* (2024) Engineering Mesoscopic 3D Tumor Models with a Self-Organizing Vascularized Matrix. Adv Mater 36: e2303196.}