Engineered cell-degradable poly(2-alkyl-2-oxazoline) hydrogel for epicardial placement of mesenchymal stem cells for myocardial repair
Autor: | Burcu Colak, Ken Suzuki, Laura Fields, Piaopiao Luo, Yaqi You, Julien E. Gautrot, Kazuya Kobayashi, Edward J. Cozens |
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Rok vydání: | 2021 |
Předmět: |
Angiogenesis
Cell Myocardial Infarction Biophysics Pro-angiogenic Infarction Biocompatible Materials Stem cell delivery Bioengineering 02 engineering and technology Article Biomaterials Cardiac repair 03 medical and health sciences Downregulation and upregulation Poly(2-alkyl-2-oxazoline) medicine Animals 030304 developmental biology 0303 health sciences Chemistry Stem Cells Mesenchymal stem cell Hydrogels Mesenchymal Stem Cells Engineered hydrogels 021001 nanoscience & nanotechnology medicine.disease In vitro Rats Cell biology medicine.anatomical_structure Mechanics of Materials Self-healing hydrogels Ceramics and Composites Stem cell 0210 nano-technology Thiol-ene coupling |
Zdroj: | Biomaterials |
ISSN: | 0142-9612 |
Popis: | Epicardial placement of mesenchymal stromal cells (MSCs) is a promising strategy for cardiac repair post-myocardial infarction, but requires the design of biomaterials to maximise the retention of donor cells on the heart surface and control their phenotype. To this end, we propose the use of a poly(2-alkyl-2-oxazoline) (POx) derivative, based on 2-ethyl-2-oxazoline and 2-butenyl-2-oxazoline. This POx polymer can be cured rapidly (less than 2 min) via photo-irradiation due to the use of di-cysteine cell degradable peptides. We report that the cell-degradable properties of the resulting POx hydrogels enables the regulation of cell protrusion in corresponding 3D matrices and that this, in turn, regulates the secretory phenotype of MSCs. In particular, the expression of pro-angiogenic genes was upregulated in partially cell-degradable POx hydrogels. Improved angiogenesis was confirmed in an in vitro microfluidic assay. Finally, we confirmed that, owing to the excellent tissue adhesive properties of thiol-ene crosslinked hydrogels, the epicardial placement of MSC-loaded POx hydrogels promoted the recovery of cardiac function and structure with reduced interstitial fibrosis and improved neovascular formation in a rat myocardial infarction model. This report demonstrates that engineered synthetic hydrogels displaying controlled mechanical, cell degradable and bioactive properties are particularly attractive candidates for the epicardial placement of stem cells to promote cardiac repair post myocardial infarction. |
Databáze: | OpenAIRE |
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