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

Author:

Wu Dongwei1ORCID,Pang Shumin2ORCID,Berg Johanna1,Mei Yikun1ORCID,Ali Ahmed S. M.1,Röhrs Viola1,Tolksdorf Beatrice1ORCID,Hagenbuchner Judith3ORCID,Ausserlechner Michael J.3ORCID,Deubzer Hedwig E.4ORCID,Gurlo Aleksander2ORCID,Kurreck Jens1ORCID

Affiliation:

1. Chair of Applied Biochemistry Technische Universität Berlin Gustav‐Meyer‐Allee 25 13355 Berlin Germany

2. Chair of Advanced Ceramic Materials Technische Universität Berlin Straße des 17. Juni 135 10623 Berlin Germany

3. Department of Pediatrics I and 3D Bioprinting Lab Medical University Innsbruck Innsbruck A‐6020 Austria

4. Department of Pediatric Hematology and Oncology Charité‐Universitätsmedizin Berlin 13353 Berlin Germany

Abstract

Abstract3D 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.

Funder

Einstein Stiftung Berlin

Stiftung zur Förderung der Erforschung von Ersatz- und Ergänzungsmethoden zur Einschränkung von Tierversuchen

China Scholarship Council

Publisher

Wiley

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