Host immune competence and local ischemia affects the functionality of engineered vasculature.
OBJECTIVE
Localized and sustained delivery of vascular endothelial growth factor (VEGF) is a promising approach to overcome the limited efficacy of bolus delivery. The authors examined the effects of host immune competence and local ischemia on the functionality of new vessel networks formed with this approach.


METHODS
Vessel structure and perfusion resulting from implantation of porous 85:15 poly(lactide-co-glycolide) scaffolds releasing VEGF165 were measured in both subcutaneous tissue and ischemic hindlimbs of immune competent C57BL/6 and immune deficient SCID mice.


RESULTS
Sustained VEGF delivery resulted in a similar approximately 100% increase in vessel density within scaffolds in both implant sites, and both animal models. However, the resulting perfusion within scaffolds implanted in subcutaneous tissue increased modestly versus control (18-35%), while perfusion increased 52-110% above control when VEGF-releasing scaffolds were placed in ischemic hindlimbs of C57BL/6 or SCID mice. VEGF delivery improved perfusion in the entire ischemic limb (55 +/- 18% of the normal value by week 6; 138% increase over control) in SCID mice. Although C57BL/6 mice demonstrated spontaneous recovery from ischemia, VEGF delivery accelerated recovery as compared to control.


CONCLUSIONS
Localized and sustained VEGF delivery can create functional vasculature that amplifies recovery of tissue ischemia. However, increases in local and regional perfusion were highly dependent on the implantation site and the animal model.
Chen
Ruth R
RR
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Snow
Jonathan K
JK
Palmer
Jack P
JP
Lin
Angela S
AS
Duvall
Craig L
CL
Guldberg
Robert E
RE
Mooney
David J
DJ
D000818:Animals; D001672:Biocompatible Materials; D016319:Corrosion Casting; D016503:Drug Delivery Systems; D006614:Hindlimb / Q000098:blood supply / Q000276:immunology; D007121:Immunocompetence / Q000502:physiology*; D007511:Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000276:immunology*; D011098:Polyglactin 910; D040521:Subcutaneous Tissue / Q000098:blood supply / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D001672:Biocompatible Materials; D042461:Vascular Endothelial Growth Factor A; D011098:Polyglactin 910