Engineering poly(dehydroalanine)-based gels via droplet-based microfluidics: from bulk to microspheres

Soft Matter, vol. 20, pp. 6231–6246

Abstract

Biomedical applications such as drug delivery, tissue engineering, and functional surface coating rely on switchable adsorption and desorption of specialized guest molecules. Poly(dehydroalanine), a polyzwitterion containing pH-dependent positive and negative charges, shows promise for such reversible loading, especially when integrated into a gel network. Herein, we present the fabrication of poly(dehydroalanine)-derived gels of different size scales and evaluate them with respect to their practical use in biomedicine. Already existing protocols for bulk gelation were remodeled to derive suitable reaction conditions for droplet-based microfluidic synthesis. Depending on the layout of the microfluidic chip, microgels with a size of approximately 30 μm or 200 μm were obtained, whose crosslinking density can be increased by implementing a multi-arm crosslinker. We analyzed the effects of the crosslinker species on composition, permeability, and softness and show that the microgels exhibit advantageous properties inherent to zwitterionic polymer systems, including high hydrophilicity as well as pH- and ionic strength-sensitivity. We demonstrate pH-regulated uptake and release of fluorescent model dyes before testing the adsorption of a small antimicrobial peptide, LL-37. Quantification of the peptide accommodated within the microgels reveals the impact of size and crosslinking density of the microgels. Biocompatibility of the microgels was validated by cell tests.

Authors 9

1. Hannah F. Mathews Aachen DWI - Leibniz Institute for Interactive Materials Institute of 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 of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

2. Tolga Çeper

   Friedrich Schiller University Jena

   Affiliation as printed

   Center for Energy and Environmental Chemistry Jena (CEEC), Friedrich-Schiller-University Jena, Philosophenweg 7a, 07743 Jena, Germany

   Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University Jena, Humboldtstr. 10, 07743 Jena, Germany

   Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Philosophenweg 7, 07743 Jena, Germany

3. Tobias Speen Aachen DWI - Leibniz Institute for Interactive Materials Institute of 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 of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

4. Céline Bastard Aachen DWI - Leibniz Institute for Interactive Materials Institute of 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 of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

5. Selin Bulut Aachen DWI - Leibniz Institute for Interactive Materials Institute of 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 of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

6. Maria I. Pieper Aachen DWI - Leibniz Institute for Interactive Materials Institute of 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 of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

7. Felix Helmut Schacher

   Friedrich Schiller University Jena

   Affiliation as printed

   Center for Energy and Environmental Chemistry Jena (CEEC), Friedrich-Schiller-University Jena, Philosophenweg 7a, 07743 Jena, Germany

   Cluster of Excellence Balance of the Microverse, Friedrich-Schiller-University Jena, Grüne Aue, 07754 Jena, Germany

   Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich-Schiller-University Jena, Humboldtstr. 10, 07743 Jena, Germany

   Jena Center for Soft Matter (JCSM), Friedrich-Schiller-University Jena, Philosophenweg 7, 07743 Jena, Germany

8. Laura De Laporte Aachen DWI - Leibniz Institute for Interactive Materials Institute of Applied Medical Engineering Department of Advanced Materials for Biomedicine Institute of Technical and Macromolecular Chemistry

   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 Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany

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

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

   Affiliation as printed

   Aachen Maastricht Institute for Biobased Materials (AMIBM), Brightland Chemelot Campus, Maastricht University, 6167 RD Geleen, The Netherlands

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

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Worringer Weg 2, 52074 Aachen, Germany