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Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

García, José R. ; Clark, Amy Y. ; García, Andrés J.

Journal of biomedical materials research. Part A, 2016-04, Vol.104 (4), p.889-900 [Periódico revisado por pares]

United States: Blackwell Publishing Ltd

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Título:
Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects
Autor: García, José R. ; Clark, Amy Y. ; García, Andrés J.
Assuntos: Animals ; Biocompatible Materials - chemistry ; Biocompatible Materials - metabolism ; Biomedical materials ; Blood vessels ; Bone Regeneration - drug effects ; Bones ; cell adhesion ; Defects ; Drug Delivery Systems - methods ; Human Umbilical Vein Endothelial Cells ; Humans ; Hydrogels ; Hydrogels - chemistry ; Hydrogels - metabolism ; Integrin alpha2beta1 - metabolism ; Integrin alphaVbeta3 - metabolism ; Male ; mesenchymal stem cells ; Mice, Inbred C57BL ; Neovascularization, Physiologic - drug effects ; Peptides ; Peptides - chemistry ; Peptides - metabolism ; Polyethylene Glycols - chemistry ; Polyethylene Glycols - metabolism ; Radius - injuries ; Radius - physiology ; Regeneration ; Rheology ; Surgical implants ; Vascular Endothelial Growth Factor A - administration & dosage ; Vascular Endothelial Growth Factor A - pharmacology ; vascularization
É parte de: Journal of biomedical materials research. Part A, 2016-04, Vol.104 (4), p.889-900
Notas: Cell and Tissue Engineering NIH Biotechnology Training Grant (to J.R.G.) - No. T32-GM008433
ark:/67375/WNG-KZ2L042Q-T
ArticleID:JBMA35626
istex:C928E9391565FF3DA98E2FFDEB694566880F7DC0
National Institutes of Health (NIH) - No. R01-AR062368 and R01-AR062920
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical‐size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin‐specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease‐degradable, VEGF‐loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple‐helical, α2β1 integrin‐specific peptide GGYGGGP(GPP)5GFOGER(GPP)5GPC (GFOGER) or an αvβ3 integrin‐targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation‐dependent release of the protein while maintaining VEGF bioactivity. When applied to critical‐size segmental defects in the murine radius, GFOGER‐functionalized VEGF‐free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD‐functionalized VEGF‐free hydrogels. VEGF‐loaded RGD hydrogels increased vascularization compared to VEGF‐free RGD hydrogels, but the levels of vascularization for these VEGF‐containing RGD hydrogels were similar to those of VEGF‐free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF‐free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF‐free RGD hydrogels. These findings demonstrate the importance of integrin‐specificity in engineering constructs for vascularization and associated bone regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 889–900, 2016.
Editor: United States: Blackwell Publishing Ltd
Idioma: Inglês

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Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects

García, José R. ; Clark, Amy Y. ; García, Andrés J.

United States: Blackwell Publishing Ltd

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