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Interactions of methacryloylated gelatin and heparin modulate physico-chemical properties of hydrogels and release of vascular endothelial growth factor

: Claaßen, Christiane; Southan, Alexander; Grübel, Jana; Tovar, Günter; Borchers, Kirsten


Biomedical materials 13 (2018), Nr.5, Art. 055008, 17 S.
ISSN: 1748-6041
ISSN: 1748-605X
Fraunhofer IGB ()
cytocompatibility; design of experiment; gelatin methacryloyl; growth factor delivery; heparin methacrylate; hydrogel

Gelatin hydrogels are used as tissue engineering scaffolds and systems for controlled release due to their inherent biodegradability and biocompatibility. In this study gelatin methacryloyl(-acetyl) (GM/A) with various degrees of methacryloylation (DM) and methacryl-modified heparin (HepM) were cross-linked radically via thermal-redox initiation. Investigation of gel yields (79.4%-85.8%) and equilibrium degrees of swelling (EDS; 564.8%-750.3%) by an experimental design approach suggested interaction effects between the applied HepM mass fraction and the DM of gelatin. HepM reduced the cross-linking effectivity (gel yield) only when added to GM with low DM (83% without HepM, 79% with HepM) but not when added to GM with high DM. For EDS combined impacts of the physical and chemical nature of the applied biopolymers are indicated: the elevated hydrophilicity and low cross-linking potential of HepM enhanced EDS in GM gels with low DM (O 1.1-fold increase), and lowered the storage moduli of all GM formulations (O 1.2-fold decrease). Vascular endothelial growth factor (VEGF) loading before cross-linking of gels resulted in major loss of functional growth factor (O 0.5% release), while loading after cross-linking was successful and significant release was detected over 28 days (6.4%-10.4% release). Release kinetics were mainly controlled by the VEGF concentration used for loading, and thus VEGF release and physico-chemical properties of the hydrogels can be tuned independently from each other in a broad range.