Specific VEGF sequestering and release using peptide-functionalized hydrogel microspheres

Abstract Growth factor signaling plays an essential role in regulating processes such as tissue development, maintenance, and repair. Gene expression levels, diffusion, degradation, and sequestration by extracellular matrix components all play a role in regulating the concentration of growth factors...

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Bibliographic Details
Published in:Biomaterials 2012-04, Vol.33 (12), p.3475-3484
Main Authors: Impellitteri, Nicholas A, Toepke, Michael W, Lan Levengood, Sheeny K, Murphy, William L
Format: Article
Language:English
Subjects:
Advanced Basic Science
Amino Acid Sequence
Animals
Bioinspired
Biomimetic
Cattle
Cell Proliferation
Dentistry
ECM
Extracellular matrix
Growth factors
Human Umbilical Vein Endothelial Cells
Humans
Hydrogel, Polyethylene Glycol Dimethacrylate - chemical synthesis
Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry
Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism
Microparticle
Microspheres
Molecular Sequence Data
Peptides - chemical synthesis
Peptides - chemistry
Peptides - metabolism
Protein Binding
Serum - metabolism
Vascular Endothelial Growth Factor A - chemistry
Vascular Endothelial Growth Factor A - metabolism
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Summary:Abstract Growth factor signaling plays an essential role in regulating processes such as tissue development, maintenance, and repair. Gene expression levels, diffusion, degradation, and sequestration by extracellular matrix components all play a role in regulating the concentration of growth factors within the cellular microenvironment. Herein, we describe the synthesis and characterization of hydrogel microspheres that mimic the ability of the native extracellular matrix to reversibly bind vascular endothelial growth factor (VEGF) out of solution. A peptide ligand derived from the VEGF receptor 2 (VEGFR2) was covalently incorporated into the hydrogel microspheres in order to achieve binding affinity and specificity. In addition to being able to both bind and release VEGF in a controllable manner, the microspheres were also shown to affect human umbilical vein endothelial cell (HUVEC) proliferation. The resulting microspheres may enable new strategies to specifically upregulate or downregulate growth factor signaling in the cellular microenvironment.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.01.032