TY - JOUR

T1 - Customizable 3D-printed (Co-)cultivation systems for in vitro study of angiogenesis

AU - Siller, Ina G.

AU - Epping, Niklas Maximilian

AU - Lavrentieva, Antonina

AU - Scheper, Thomas

AU - Bahnemann, Janina

N1 - Funding Information: This research was funded by the German Research Foundation (DFG) via the Emmy Noether programme, project ID 346772917 and the publication of this article was funded by the Open Access fund of Leibniz Universit?t Hannover. The authors would like to thank Jan Ebbecke for his support in cell cultivation. Furthermore, we would like to thank Sebastian Heene and the group of Cornelia Blume (Institute of Technical Chemistry, Hannover, Germany), who kindly provided the endothelial cells. We acknowledge the corporation with Sarah Strauss and Peter Vogt, (Hannover Medical School, Hannover, Germany), who provided tissue material for AD-MSCs isolation. Finally, we would like to thank the group of Oliver Plettenburg (Institute of Organic Chemistry, Hannover, Germany) for providing the live cell imaging microscope.

PY - 2020/9/25

Y1 - 2020/9/25

N2 - Due to the ever-increasing resolution of 3D printing technology, additive manufacturing is now even used to produce complex devices for laboratory applications. Personalized experimental devices or entire cultivation systems of almost unlimited complexity can potentially be manufactured within hours from start to finish—an enormous potential for experimental parallelization in a highly controllable environment. This study presents customized 3D-printed co-cultivation systems, which qualify for angiogenesis studies. In these systems, endothelial and mesenchymal stem cells (AD-MSC) were indirectly co-cultivated—that is, both cell types were physically separated through a rigid, 3D-printed barrier in the middle, while still sharing the same cell culture medium that allows for the exchange of signalling molecules. Biochemical-based cytotoxicity assays initially confirmed that the 3D printing material does not exert any negative effects on cells. Since the material also enables phase contrast and fluorescence microscopy, the behaviour of cells could be observed over the entire cultivation via both. Microscopic observations and subsequent quantitative analysis revealed that endothelial cells form tubular-like structures as angiogenic feature when indirectly co-cultured alongside AD-MSCs in the 3D-printed co-cultivation system. In addition, further 3D-printed devices are also introduced that address different issues and aspire to help in varying experimental setups. Our results mark an important step forward for the integration of customized 3D-printed systems as self-contained test systems or equipment in biomedical applications.

AB - Due to the ever-increasing resolution of 3D printing technology, additive manufacturing is now even used to produce complex devices for laboratory applications. Personalized experimental devices or entire cultivation systems of almost unlimited complexity can potentially be manufactured within hours from start to finish—an enormous potential for experimental parallelization in a highly controllable environment. This study presents customized 3D-printed co-cultivation systems, which qualify for angiogenesis studies. In these systems, endothelial and mesenchymal stem cells (AD-MSC) were indirectly co-cultivated—that is, both cell types were physically separated through a rigid, 3D-printed barrier in the middle, while still sharing the same cell culture medium that allows for the exchange of signalling molecules. Biochemical-based cytotoxicity assays initially confirmed that the 3D printing material does not exert any negative effects on cells. Since the material also enables phase contrast and fluorescence microscopy, the behaviour of cells could be observed over the entire cultivation via both. Microscopic observations and subsequent quantitative analysis revealed that endothelial cells form tubular-like structures as angiogenic feature when indirectly co-cultured alongside AD-MSCs in the 3D-printed co-cultivation system. In addition, further 3D-printed devices are also introduced that address different issues and aspire to help in varying experimental setups. Our results mark an important step forward for the integration of customized 3D-printed systems as self-contained test systems or equipment in biomedical applications.

KW - Additive manufacturing

KW - Angiogenesis

KW - Biomaterials

KW - Biomedical application

KW - Co-cultivation

KW - Mammalian cell culture

UR - http://www.scopus.com/inward/record.url?scp=85093932826&partnerID=8YFLogxK

U2 - 10.3390/ma13194290

DO - 10.3390/ma13194290

M3 - Article

AN - SCOPUS:85093932826

VL - 13

SP - 1

EP - 17

JO - MATERIALS

JF - MATERIALS

SN - 1996-1944

IS - 19

M1 - 4290

ER -