Double network microgels based on dextran and fibrin with tunable structural, mechanical, and degradation properties

Journal of Colloid and Interface Science, vol. 700, pp. 138345

Abstract

Colloidal hydrogels, also known as microgels, are promising scaffold materials in the biomedical field. Microgels exhibit high biocompatibility, porosity, and mechanical stability, crucial in supporting cell development. Bio-based polymers, such as fibrin or dextran, are desirable for controlling the properties of microgels. The advantage of using these polymers includes producing degradable microgels that enable the release of active components. In this work, we fabricated fibrin-dextran-methacrylate (dextran-MA) interpenetrating polymer network microgels with tunable porosity, stiffness, and degradation profiles using droplet-based microfluidics. We incorporated fibrin to promote cell growth, while adding dextran-MA ensures improved structural stability of the microgels. By systematically varying the dextran-MA concentrations, we produced fibrin-dextran-MA microgels with a tunable range of stiffness, porosity, and degradation time, highlighting the material's versatility for biomedical applications. In particular, increasing the dextran-MA content reduced pore size, thereby offering a means to control the encapsulation and release of active components. Degradation studies using plasminogen and dextranase revealed that the degradation of the microgels strongly depended on the polymer concentration. This dependency allows controlling the degradation time and the release kinetics of active components, e.g., hepatocyte growth factor (HGF). HGF encapsulated in fibrin microgels was released rapidly through diffusion, while the release from fibrin-dextran microgels was delayed until enzymatic degradation. This delayed degradation of microgels demonstrates the potential to use the microgels for programmable release. Encapsulation of HGF in fibrin and fibrin-dextran-MA microgels promoted the spreading of human mesenchymal stem cells on the microgels, highlighting their potential for personalized Tissue Engineering applications. Our studies reveal that engineered microgels composed of fibrin and dextran-MA can be used as colloidal building blocks to design biomaterials with tailored stiffness, porosity, degradation, and programmed release behavior.

Authors 11

1. Shannon Anna Jung Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

2. Hannah Küttner Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

3. Svenja Wein Aachen BioInterface Group Institute of Pathology

   RWTH Aachen University

   Affiliation as printed

   Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany; Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany

4. Hanna Malyaran Aachen BioInterface Group Interdisciplinary Center for Clinical Research (IZKF)

   RWTH Aachen University

   Affiliation as printed

   Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany; Interdisciplinary Centre for Clinical Research, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany

5. Luca Anna Reicher Aachen BioInterface Group Interdisciplinary Center for Clinical Research (IZKF)

   RWTH Aachen University

   Affiliation as printed

   Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany; Interdisciplinary Centre for Clinical Research, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany

6. Caroline Schmidt Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

7. Nicole Marcinkowska Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

8. Miriam Aischa Al Enezy‐Ulbrich Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany

9. Stephan Rütten Aachen

   RWTH Aachen University

   Affiliation as printed

   Electron Microscopic Facility University Clinics, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany

10. Sabine Neuß Aachen BioInterface Group Institute of Pathology

    RWTH Aachen University

    Affiliation as printed

    Helmholtz Institute for Biomedical Engineering, BioInterface Group, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany; Institute of Pathology, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany

11. Andrij Pich corresponding Aachen DWI - Leibniz Institute for Interactive Materials Institute for Technical and Macromolecular Chemistry

    DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

    Affiliation as printed

    DWI-Leibniz Institute for Interactive Materials, RWTH Aachen University, Forckenbeckstraße 50, 52074 Aachen, Germany; Institute for Technical and Macromolecular Chemistry, RWTH Aachen University, Worringerweg 2, 52074 Aachen, Germany. Electronic address: pich@dwi.rwth-aachen.de