The dosage dependence of VEGF stimulation on scaffold neovascularisation.
Growth factors are often used in tissue regeneration to stimulate vascularisation of polymeric scaffolds, with vascular endothelial growth factor (VEGF) having been extensively studied for short-term vessel ingrowth. We have therefore evaluated the effect of different concentrations of VEGF on the vascularisation of a porous scaffold in the short-, intermediate- and long-term, by delivering 15, 150 and 1500ng VEGF/day to polyurethane scaffolds by osmotic pumps for up to 6 weeks. An increased vascularisation months after termination of VEGF delivery was only achieved with 150ng/day (46%, p<0.05). This dosage consistently showed elevated levels of vascularisation (144, 125, 160 and 60% above PBS controls at 10, 20, 30 and 42 days, respectively, p<0.05), whilst the vessels induced by the highest dosage, though initially maximally elevated (265 and 270% at 10 and 20 days, p<0.05) tended to regress after 20 days of VEGF delivery. Pericyte coverage was decreased at 20 days for the highest dosage (30%, p<0.05). Lectin perfusion demonstrated that vessels within the scaffold were connected to the host vasculature at all time points and perfusion was substantially raised by VEGF delivery at day 20. These results suggest concentration of VEGF plays a critical role in the nature and persistence of vasculature formed in a tissue regenerative scaffold.
Cardiovascular Research Unit, Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town, Department of Health Sciences, 203 Cape Heart Centre, Anzio Road, Observatory, 7925 Cape Town, South Africa. neil.davies@uct.ac.za
Neil
N
Davies
Stephan
S
Dobner
Deon
D
Bezuidenhout
Christian
C
Schmidt
Michael
M
Beck
Andreas H
AH
Zisch
Peter
P
Zilla
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A