Angiogenesis in a microvascular construct for transplantation depends on the method of chamber circulation.
Effective tissue prevascularization depends on new vessel growth and subsequent progression of neovessels into a stable microcirculation. Isolated microvessel fragments in a collagen-based microvascular construct (MVC) spontaneously undergo angiogenesis in static conditions in vitro but form a new microcirculation only when implanted in vivo. We have designed a bioreactor, the dynamic in vitro perfusion (DIP) chamber, to culture MVCs in vitro with perfusion. By altering bioreactor circulation, microvessel fragments in the DIP chamber either maintained stable, nonsprouting, patent vessel morphologies or sprouted endothelial neovessels that extended out into the surrounding collagen matrix (i.e., angiogenesis), yielding networks of neovessels within the MVC. Neovessels formed in regions of the construct predicted by simulation models to have the steepest gradients in oxygen levels and expressed hypoxia inducible factor-1alpha. By altering circulation conditions in the DIP chamber, we can control, possibly by modulating hypoxic stress, prevascularizing activity in vitro.
Division of Cardiovascular Therapeutics, Cardiovascular Innovation Institute, Louisville, KY 40202, USA.
Carlos C
CC
Chang
Sara S
SS
Nunes
Scott C
SC
Sibole
Laxminarayanan
L
Krishnan
Stuart K
SK
Williams
Jeffrey A
JA
Weiss
James B
JB
Hoying
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D019149:Bioreactors; D001807:Blood Vessel Prosthesis; D002478:Cells, Cultured; D004058:Diffusion / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D055806:Microvessels / Q000166:cytology / Q000187:drug effects / Q000637:transplantation*; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen