Improvement of vascularization of PLGA scaffolds by inosculation of in situ-preformed functional blood vessels with the host microvasculature.

Abstract

We analyzed, in vivo, whether the establishment of blood supply to implanted scaffolds can be accelerated by inosculation of an in situ-preformed microvascular network with the host microvasculature. A rapid vascularization is crucial for the survival of scaffold-based transplanted tissue constructs. Poly-lactic-glycolic acid scaffolds were implanted into the flank of balb/c or green fluorescent protein (GFP)-transgenic mice for 20 days to create in situ a new microvascular network within the scaffolds. The prevascularized scaffolds were then transferred into the dorsal skinfold chamber of isogeneic recipient mice. Nonvascularized poly-lactic-glycolic acid scaffolds served as controls. Vascularization, blood perfusion, and cell survival of the implants were analyzed over 14 days using intravital fluorescence microscopy, histology, and immunohistochemistry. Our results demonstrate that establishment of blood perfusion of prevascularized scaffolds is significantly accelerated and improved (136.7 +/- 23.2 pl/s) when compared with controls (6.9 +/- 1.9 pl/s), because the in situ-preformed microvessels were reperfused by forming interconnections to the host microvasculature. Apoptotic cell death within the implants was found only during the first 3 to 6 days after scaffold implantation during lack of blood perfusion, but not during the further 14-day observation period. Inosculation of in situ-preformed functional blood vessels represents a promising approach to improve the blood supply to implanted tissue constructs.