TY  - JOUR
A1  - Lübtow, Michael M.
A1  - Lorson, Thomas
A1  - Finger, Tamara
A1  - Gröber-Becker, Florian-Kai
A1  - Luxenhofer, Robert
T1  - Combining Ultra-High Drug-Loaded Micelles and Injectable Hydrogel Drug Depots for Prolonged Drug Release
JF  - Macromolecular Chemistry and Physics
N2  - Hydrogel‐based drug depot formulations are of great interest for therapeutic applications. While the biological activity of such drug depots is often characterized well, the influence of incorporated drug or drug‐loaded micelles on the gelation properties of the hydrogel matrix is less investigated. However, the latter is of great importance from fundamental and application points of view as it informs on the physicochemical interactions of drugs and water‐swollen polymer networks and it determines injectability, depot stability, as well as drug‐release kinetics. Here, the impact of incorporated drug, neat polymer micelles, and drug‐loaded micelles on the viscoelastic properties of a cytocompatible hydrogel is investigated systematically. To challenge the hydrogel with regard to the desired application as injectable drug depot, curcumin (CUR) is chosen as a model compound due to its very low‐water solubility and limited stability. CUR is either directly solubilized by the hydrogel or pre‐incorporated into polymer micelles. Interference of CUR with the temperature‐induced gelation process can be suppressed by pre‐incorporation into polymer micelles forming a binary drug delivery system. Drug release from a collagen matrix is studied in a trans‐well setup. Compared to direct injection of drug formulations, the hydrogel‐based systems show improved and extended drug release over 10 weeks.
KW  - curcumin
KW  - drug depots
KW  - drug-loaded hydrogels
KW  - poly(2-oxazine)
KW  - sustained release
KW  - poly(2- oxazoline)
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208115
VL  - 221
IS  - 1
ER  - 
TY  - JOUR
A1  - Hahn, Lukas
A1  - Beudert, Matthias
A1  - Gutmann, Marcus
A1  - Keßler, Larissa
A1  - Stahlhut, Philipp
A1  - Fischer, Lena
A1  - Karakaya, Emine
A1  - Lorson, Thomas
A1  - Thievessen, Ingo
A1  - Detsch, Rainer
A1  - Lühmann, Tessa
A1  - Luxenhofer, Robert
T1  - From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking
JF  - Macromolecular Bioscience
N2  - Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.
KW  - chemical crosslinking
KW  - biofabrication
KW  - bioprinting
KW  - hydrogels
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257542
VL  - 21
IS  - 10
ER  -