How Does Temporal and Sequential Delivery of Multiple Growth Factors Affect Vascularization Inside 3D Hydrogels?

Advanced Therapeutics, vol. 7

Abstract

Abstract Vasculogenesis and angiogenesis are leveraged by orchestrated secretion of several growth factors. Mimicking this process in vitro can maximize vascularization inside 3D cell cultures. While the role of individual growth factors, such as vascular endothelial growth factor, Ephrin‐B2, angiopoietins, and platelet‐derived growth factor‐BB (PDGF‐BB) is well studied, the temporal influence of growth factor secretion, and the effect of their concentrations and combinations on in vitro vascularization inside hydrogels, have not been systematically investigated. Here, combinations of angiopoietin‐1, angiopoietin‐2, and PDGF‐BB improve vascularization of a human umbilical vein endothelial cells‐fibroblast coculture inside polyethylene glycol‐based hydrogels the most, while the optimal concentrations and time points of growth factor addition are determined. Moreover, fibroblasts, pericytes, and mesenchymal stem cells (MSCs) are compared as supporting cells, of which MSCs best promote vascularization in coculture. Additionally, the resulting blood vessels align with magnetically oriented rod‐shaped microgels when cultured inside the Anisogel. To mimic fibrosis, transforming growth factor‐beta is added, resulting in significantly smaller vessels and more collagen secretion. This in vitro study reveals that a cascade of growth factors can improve vascular formation in 3D hydrogels, which is important to create viable tissue‐engineered constructs for therapies and in vitro healthy and diseased tissue models.

Authors 9

1. Céline Bastard Aachen Institute for Technical and Macromolecular Chemistry Institute of Applied Medical Engineering (AME) Department of Advanced Materials for Biomedicine (AMB) Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine

   DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen University Worringerweg 1–2 52074 Aachen Germany

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

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

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

   DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen University Worringerweg 1–2 52074 Aachen Germany

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

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

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

   DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

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

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

4. Mieke A. Dewerchin

   VIB-KU Leuven Center for Cancer Biology · KU Leuven

   Affiliation as printed

   Laboratory of Angiogenesis and Vascular Metabolism Center for Cancer Biology (CCB), VIB, and Department of Oncology KU Leuven Campus Gasthuisberg ON4, Herestraat 49‐902 Leuven 3000 Belgium

5. Peter Sprycha Aachen Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen University Worringerweg 1–2 52074 Aachen Germany

6. Christopher J. Licht Aachen Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen University Worringerweg 1–2 52074 Aachen Germany

7. Arne Lüken Aachen Chemical Process Engineering

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   Chemical Process Engineering RWTH Aachen University Forckenbeckstr. 51 52074 Aachen Germany

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

8. Matthias Weßling Aachen Chemical Process Engineering

   VIB-KU Leuven Center for Cancer Biology · DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University · KU Leuven

   Affiliation as printed

   Chemical Process Engineering RWTH Aachen University Forckenbeckstr. 51 52074 Aachen Germany

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Laboratory of Angiogenesis and Vascular Metabolism Center for Cancer Biology (CCB), VIB, and Department of Oncology KU Leuven Campus Gasthuisberg ON4, Herestraat 49‐902 Leuven 3000 Belgium

   Chemical Process Engineering, RWTH Aachen University, Forckenbeckstr. 51, 52074 Aachen, Germany

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

   DWI – Leibniz Institute for Interactive Materials · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   DWI – Leibniz‐Institute for Interactive Materials Forckenbeckstr. 50 52074 Aachen Germany

   Institute for Technical and Macromolecular Chemistry RWTH Aachen University Worringerweg 1–2 52074 Aachen Germany

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

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