Bioprinting of Perfusable Vascularized Organ Models for Drug Development via Sacrificial-Free Direct Ink Writing

3D bioprinting enables the fabrication of human organ models that can be used for various fields of biomedical research, including oncology and infection biology. An important challenge, however, remains the generation of vascularized, perfusable 3D models that closely simulate natural physiology. Here, a novel direct ink writing (DIW) approach is described that can produce vascularized organ models without using sacrificial materials during fabrication. The high resolution of the method allows the one-step generation of various sophisticated hollow geometries. This sacrificial-free DIW (SF-DIW) approach is used to fabricate hepatic metastasis models of various cancer types and different formats for investigating the cytostatic activity of anti-cancer drugs. To this end, the models are incorporated into a newly developed perfusion system with integrated micropumps and an agar casting step that improves the physiological features of the bioprinted tissues. It is shown that the hepatic environment of the tumor models is capable of activating a prodrug, which inhibits breast cancer growth. This versatile SF-DIW approach is able to fabricate complicated perfusable constructs or microfluidic chips in a straightforward and cost-efficient manner. It can also be easily adapted to other cell types for generating vascularized organ tissues or cancer models that may support the development of new therapeutics. An efficient 3D bioprinting approach is established for direct creation of perfusable vascularized human organ models without sacrificial materials. Combined with an original miniature perfusion system, it enhances the physiological features of the in vitro liver model. The perfused liver model facilitates the growth of metastatic cancer spheroids, and shows potential application in drug evaluation even including prodrug bioactivation. image