Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation.
OBJECTIVE
Biological mechanisms of tissue regeneration are often complex, involving the tightly coordinated spatial and temporal presentation of multiple factors. We investigated whether spatially compartmentalized and sequential delivery of factors can be used to pattern new blood vessel formation.


METHODS
A porous bi-layered poly(lactide-co-glycolide) (PLG) scaffold system was used to locally present vascular endothelial growth factor (VEGF) alone in one spatial region, and sequentially deliver VEGF and platelet-derived growth factor (PDGF) in an adjacent region. Scaffolds were implanted in severely ischemic hindlimbs of SCID mice for 2 and 6 weeks, and new vessel formation was quantified within the scaffolds.


RESULTS
In the compartment delivering a high dose of VEGF alone, a high density of small, immature blood vessels was observed at 2 weeks. Sequential delivery of VEGF and PDGF led to a slightly lower blood vessel density, but vessel size and maturity were significantly enhanced. Results were similar at 6 weeks, with continued remodeling of vessels in the VEGF and PDGF layer towards increased size and maturation.


CONCLUSIONS
Spatially localizing and temporally controlling growth factor presentation for angiogenesis can create spatially organized tissues.
Chen
Ruth R
RR
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Silva
Eduardo A
EA
Yuen
William W
WW
Mooney
David J
DJ
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000254:growth & development*; D016503:Drug Delivery Systems; D006614:Hindlimb / Q000098:blood supply; D007150:Immunohistochemistry; D007511:Ischemia / Q000473:pathology; D051379:Mice; D015233:Models, Statistical; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A