Deciphering the relative roles of matrix metalloproteinase‐ and plasmin‐mediated matrix degradation during capillary morphogenesis using engineered hydrogels
| Autor: | Jeffrey A. Beamish, Andrew J. Putnam, David S. Cleveland, Likitha Nimmagadda, Benjamin A. Juliar, Megan E. Busch |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Materials science Plasmin medicine.medical_treatment Biomedical Engineering Morphogenesis Neovascularization Physiologic macromolecular substances 02 engineering and technology Matrix metalloproteinase Article Biomaterials Extracellular matrix 03 medical and health sciences Vasculogenesis Human Umbilical Vein Endothelial Cells medicine Humans Collagenases Fibrinolysin Fibroblast Protease technology industry and agriculture Hydrogels Fibroblasts 021001 nanoscience & nanotechnology Coculture Techniques Capillaries Extracellular Matrix Cell biology 030104 developmental biology medicine.anatomical_structure Self-healing hydrogels 0210 nano-technology medicine.drug |
| Zdroj: | J Biomed Mater Res B Appl Biomater |
| ISSN: | 1552-4981 1552-4973 |
| DOI: | 10.1002/jbm.b.34341 |
| Popis: | Extracellular matrix (ECM) remodeling is essential for the process of capillary morphogenesis. Here we employed synthetic poly(ethylene glycol) (PEG) hydrogels engineered with proteolytic specificity to either matrix metalloproteinases (MMPs), plasmin, or both to investigate the relative contributions of MMP- and plasmin-mediated ECM remodeling to vessel formation in a 3D-model of capillary self-assembly analogous to vasculogenesis. We first demonstrated a role for both MMP- and plasmin-mediated mechanisms of ECM remodeling in an endothelial-fibroblast co-culture model of vasculogenesis in fibrin hydrogels using inhibitors of MMPs and plasmin. When this co-culture model was employed in engineered PEG hydrogels with selective protease sensitivity, we observed robust capillary morphogenesis only in MMP-sensitive matrices. Fibroblast spreading in plasmin-selective hydrogels confirmed this difference was due to protease preference by endothelial cells, not due to limitations of the matrix itself. In hydrogels engineered with crosslinks that were dually susceptible to MMPs and plasmin, capillary morphogenesis was unchanged. These findings highlight the critical importance of MMP-mediated degradation during vasculogenesis and provide strong evidence to justify the preferential selection of MMP-degradable peptide crosslinkers in synthetic hydrogels used to study vascular morphogenesis and promote vascularization. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2507-2516, 2019. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text