Transformative Materials to Create 3D Functional Human Tissue Models In Vitro in a Reproducible Manner

Advanced Healthcare Materials, vol. 12, pp. e2301030

Abstract

Recreating human tissues and organs in the petri dish to establish models as tools in biomedical sciences has gained momentum. These models can provide insight into mechanisms of human physiology, disease onset, and progression, and improve drug target validation, as well as the development of new medical therapeutics. Transformative materials play an important role in this evolution, as they can be programmed to direct cell behavior and fate by controlling the activity of bioactive molecules and material properties. Using nature as an inspiration, scientists are creating materials that incorporate specific biological processes observed during human organogenesis and tissue regeneration. This article presents the reader with state-of-the-art developments in the field of in vitro tissue engineering and the challenges related to the design, production, and translation of these transformative materials. Advances regarding (stem) cell sources, expansion, and differentiation, and how novel responsive materials, automated and large-scale fabrication processes, culture conditions, in situ monitoring systems, and computer simulations are required to create functional human tissue models that are relevant and efficient for drug discovery, are described. This paper illustrates how these different technologies need to converge to generate in vitro life-like human tissue models that provide a platform to answer health-based scientific questions.

Authors 27

1. José Gerardo‐Nava Aachen Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME)

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

   DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

2. Jitske Jansen Aachen Institute of Experimental Medicine and Systems Biology Department of Medicine 2

   Erasmus MC · Universitätsklinikum Aachen · Erasmus MC Transplant Institute · RWTH Aachen University

   Affiliation as printed

   Department of Internal Medicine Nephrology and Transplantation Erasmus Medical Center Dr. Molewaterplein 40 Rotterdam 3584CG The Netherlands

   Institute of Experimental Medicine and Systems Biology and Department of Medicine 2 RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

   Institute of Experimental Medicine and Systems Biology and Department of Medicine 2 RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

3. Daniel Günther Aachen Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

   DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine RWTH Aachen University Worringerweg 2 52074 Aachen Germany

   Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

4. Laura Klasen Aachen Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine RWTH Aachen University Worringerweg 2 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry (ITMC), Advanced Materials for Biomedicine, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

5. Anja Lena Thiebes Aachen

   Maastricht University · RWTH Aachen University

   Affiliation as printed

   Aachen‐Maastricht Institute for Biobased Materials Faculty of Science and Engineering Maastricht University Brightlands Chemelot Campus, Urmonderbaan 22 6167 RD Geleen The Netherlands

   Department of Biohybrid and Medical Textiles (BioTex) AME – Institute of Applied Medical Engineering Helmholtz Institute RWTH Aachen University Pauwelsstraße 20 52074 Aachen Germany

   Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands

6. Bastian Nießing Aachen

   Fraunhofer Institute for Production Technology IPT

   Affiliation as printed

   Fraunhofer Institute for Production Technology IPT Steinbachstraße 17 52074 Aachen Germany

7. Cédric Bergerbit Aachen

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

8. Anna A. Meyer Aachen Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine RWTH Aachen University Worringerweg 2 52074 Aachen Germany

   Institute of Technical and Macromolecular Chemistry (ITMC), Advanced Materials for Biomedicine, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

9. John Linkhorst Aachen Department of Chemical Process Engineering (AVT.CVT)

   RWTH Aachen University

   Affiliation as printed

   Department of Chemical Process Engineering (AVT.CVT) RWTH Aachen University Forckenbeckstraße 51 52074 Aachen Germany

10. Mareike Barth Aachen Department of Cardiac Surgery

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Cardiac Surgery RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

11. Payam Akhyari Aachen Department of Cardiac Surgery

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Cardiac Surgery RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

12. Julia Stingl Aachen Institute of Clinical Pharmacology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Clinical Pharmacology University Hospital of RWTH Wendlingweg 2 52074 Aachen Germany

    Institute of Clinical Pharmacology, University Hospital of RWTH, Wendlingweg 2, 52074 Aachen, Germany

13. Saskia Kathi Nagel Aachen Applied Ethics Group

    RWTH Aachen University

    Affiliation as printed

    Applied Ethics Group RWTH Aachen University Theaterplatz 14 52062 Aachen Germany

    Applied Ethics Group, RWTH Aachen University, Theaterplatz 14, 52062 Aachen, Germany

14. Thomas Stiehl Aachen Institute for Computational Biomedicine-Disease Modeling

    RWTH Aachen University

    Affiliation as printed

    Institute for Computational Biomedicine – Disease Modeling RWTH Aachen University Templergraben 55 52062 Aachen Germany

15. Angelika Lampert Aachen Institute of Neurohysiology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Neurohysiology RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

16. Rudolf E. Leube Aachen Institute of Molecular and Cellular Anatomy (MOCA)

    RWTH Aachen University

    Affiliation as printed

    Institute of Molecular and Cellular Anatomy RWTH Aachen University Wendlingweg 2 52057 Aachen Germany

    Institute of Molecular and Cellular Anatomy, RWTH Aachen University, Wendlingweg 2, 52057 Aachen, Germany

17. Matthias Weßling Aachen Department of Chemical Process Engineering (AVT.CVT)

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

    Department of Chemical Process Engineering (AVT.CVT) RWTH Aachen University Forckenbeckstraße 51 52074 Aachen Germany

18. Francesca Santoro Aachen Neuroelectronic Interfaces Research Group

    RWTH Aachen University

    Affiliation as printed

    Neuroelectronic Interfaces Research Group RWTH Aachen University Templergraben 55 52062 Aachen Germany

    Neuroelectronic Interfaces Research Group, RWTH Aachen University, Templergraben 55, 52062 Aachen, Germany

19. Sven Ingebrandt Aachen Institute of Materials in Electrical Engineering 1

    RWTH Aachen University

    Affiliation as printed

    Institute of Materials in Electrical Engineering 1 RWTH Aachen University Sommerfeldstraße 18 52074 Aachen Germany

20. Stefan Jockenhoevel Aachen

    Maastricht University · RWTH Aachen University

    Affiliation as printed

    Aachen‐Maastricht Institute for Biobased Materials Faculty of Science and Engineering Maastricht University Brightlands Chemelot Campus, Urmonderbaan 22 6167 RD Geleen The Netherlands

    Department of Biohybrid and Medical Textiles (BioTex) AME – Institute of Applied Medical Engineering Helmholtz Institute RWTH Aachen University Pauwelsstraße 20 52074 Aachen Germany

    Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands

21. Andreas Peter Herrmann Aachen Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine

    RWTH Aachen University

    Affiliation as printed

    Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

    Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine RWTH Aachen University Worringerweg 2 52074 Aachen Germany

    Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

22. Horst Fischer Aachen Department of Dental Materials and Biomaterials Research

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Dental Materials and Biomaterials Research RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

23. Wolfgang Wagner Aachen Institute for Stem Cell Biology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Helmholtz‐Institute for Biomedical Engineering RWTH Aachen University Pauwelsstraße 20 52074 Aachen Germany

    Institute for Stem Cell Biology RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

24. Robert Heinrich Schmitt Aachen Laboratory for Machine Tools and Production Engineering (WZL)

    Fraunhofer Institute for Production Technology IPT · RWTH Aachen University

    Affiliation as printed

    Fraunhofer Institute for Production Technology IPT Steinbachstraße 17 52074 Aachen Germany

    Laboratory for Machine Tools and Production Engineering RWTH Aachen University Campus‐boulevard 30 52074 Aachen Germany

    Laboratory for Machine Tools and Production Engineering, RWTH Aachen University, Campus-boulevard 30, 52074 Aachen, Germany

25. Fabian M. Kiessling Aachen Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging Faculty of Medicine

    RWTH Aachen University

    Affiliation as printed

    Department of Nanomedicine and Theranostics Institute for Experimental Molecular Imaging Faculty of Medicine RWTH Aachen University Forckenbeckstraße 55 52074 Aachen Germany

26. Rafael Kramann Aachen Institute of Experimental Medicine and Systems Biology Department of Medicine 2

    Erasmus MC · Universitätsklinikum Aachen · Erasmus MC Transplant Institute · RWTH Aachen University

    Affiliation as printed

    Department of Internal Medicine Nephrology and Transplantation Erasmus Medical Center Dr. Molewaterplein 40 Rotterdam 3584CG The Netherlands

    Institute of Experimental Medicine and Systems Biology and Department of Medicine 2 RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

    Institute of Experimental Medicine and Systems Biology and Department of Medicine 2 RWTH Aachen University Hospital Pauwelsstraße 30 52074 Aachen Germany

27. Laura De Laporte corresponding Aachen Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany

    DWI – Leibniz Institute for Interactive Materials Forckenbeckstraße 50 52074 Aachen Germany

    Institute of Technical and Macromolecular Chemistry (ITMC) Advanced Materials for Biomedicine RWTH Aachen University Worringerweg 2 52074 Aachen Germany

    Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering (AME) RWTH Aachen University Hospital Center for Biohybrid Medical Systems (CMBS) Forckenbeckstraße 55 52074 Aachen Germany