Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels

Matthias Beudert; Lukas Hahn; Anselm H C Horn; Niklas Hauptstein; Heinrich Sticht; Lorenz Meinel; Robert Luxenhofer; Marcus Gutmann; Tessa Lühmann

doi:10.1016/j.jconrel.2022.04.028

Merging bioresponsive release of insulin-like growth factor I with 3D printable thermogelling hydrogels

J Control Release. 2022 Jul:347:115-126. doi: 10.1016/j.jconrel.2022.04.028. Epub 2022 May 6.

Authors

Matthias Beudert¹, Lukas Hahn², Anselm H C Horn³, Niklas Hauptstein¹, Heinrich Sticht³, Lorenz Meinel⁴, Robert Luxenhofer⁵, Marcus Gutmann⁶, Tessa Lühmann⁷

Affiliations

¹ Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany.
² Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany; Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy, Julius-Maximilians-University Würzburg, Röntgenring 11, DE-97070 Würzburg, Germany.
³ Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Fahrstraße 17, DE-91054 Erlangen, Germany; Erlangen National High Performance Computing Center (NHR@FAU), Friedrich-Alexander-Universität Erlangen-Nürnberg, Martensstraße 1, DE-91058 Erlangen, Germany.
⁴ Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany; Helmholtz Institute for RNA-based Infection Research, Josef-Schneider-Straße 2, DE-97080 Würzburg, Germany.
⁵ Functional Polymer Materials, Chair for Advanced Materials Synthesis, Institute for Functional Materials and Biofabrication, Department of Chemistry and Pharmacy, Julius-Maximilians-University Würzburg, Röntgenring 11, DE-97070 Würzburg, Germany; Soft Matter Chemistry, Department of Chemistry and Helsinki Institute of Sustainability Science, Faculty of Science, University of Helsinki, P.O. Box 55, 00014 Helsinki, Finland.
⁶ Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany. Electronic address: marcus.gutmann@uni-wuerzburg.de.
⁷ Institute for Pharmacy and Food Chemistry, University of Würzburg, DE-97074 Würzburg, Germany. Electronic address: tessa.luehmann@uni-wuerzburg.de.

PMID: 35489547
DOI: 10.1016/j.jconrel.2022.04.028

Abstract

3D printing of biomaterials enables spatial control of drug incorporation during automated manufacturing. This study links bioresponsive release of the anabolic biologic, insulin-like growth factor-I (IGF-I) in response to matrix metalloproteinases (MMP) to 3D printing using the block copolymer of poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine) (POx-b-POzi). For that, a chemo-enzymatic synthesis was deployed, ligating IGF-I enzymatically to a protease sensitive linker (PSL), which was conjugated to a POx-b-POzi copolymer. The product was blended with the plain thermogelling POx-b-POzi hydrogel. MMP exposure of the resulting hydrogel triggered bioactive IGF-I release. The bioresponsive IGF-I containing POx-b-POzi hydrogel system was further detailed for shape control and localized incorporation of IGF-I via extrusion 3D printing for future applications in biomedicine and biofabrication.

Keywords: 3D printing; Biofabrication; IGF-I; Matrix metalloproteinase; POx; Poly(2-methyl-2-oxazoline)-b-poly(2-propyl-2-oxazine); Transglutaminase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biocompatible Materials / metabolism
Hydrogels* / metabolism
Insulin-Like Growth Factor I*
Matrix Metalloproteinases / metabolism
Polymers
Printing, Three-Dimensional

Substances

Biocompatible Materials
Hydrogels
Polymers
Insulin-Like Growth Factor I
Matrix Metalloproteinases