Bioactivation of collagen matrices through sustained VEGF release from PLGA microspheres.
The success of any tissue engineering implant relies upon prompt vascularization of the cellular construct and, hence, on the ability of the scaffold to broadcast specific activation of host endothelium and guide vessel ingrowth. Vascular endothelial growth factor (VEGF) is a potent angiogenic stimulator, and if released in a controlled manner it may enhance and guide scaffold vascularization. Therefore, the aim of this work was to realize a scaffold with integrated depots able to release VEGF in a controlled rate and assess the ability of this scaffold to promote angiogenesis. VEGF-loaded poly(lactide-co-glycolide) (PLGA) microspheres were produced and included in a collagen scaffold. The release of VEGF from microspheres was tailored to be sustained over several weeks and occurred at a rate of approximately 0.6 ng/day per mg of microspheres. It was found that collagen scaffolds bioactivated with VEGF-loaded microspheres strongly enhanced endothelial cell activation and vascular sprouting both in vitro and in vivo as compared with a collagen scaffold bioactivated with free VEGF. This report demonstrates that by finely tuning VEGF release rate within a polymeric scaffold, sprouting of angiogenic vessels can be guided within the scaffolds interstices as well as broadcasted from the host tissues.
Borselli
Cristina
C
Interdisciplinary Research Centre on Biomedical Materials, University of Napoli Federico II, Naples, Italy.
Ungaro
Francesca
F
Oliviero
Olimpia
O
d'Angelo
Ivana
I
Quaglia
Fabiana
F
La Rotonda
Maria I
MI
Netti
Paolo A
PA
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003094:Collagen / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013696:Temperature; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen