Objective: 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. Background: A rapid vascularization is crucial for the survival of scaffold-based transplanted tissue constructs. Methods: 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. Results: Our results demonstrate that establishment of blood perfusion of prevascularized scaffolds is significantly accelerated and improved (136.7 Ϯ 23.2 pl/s) when compared with controls (6.9 Ϯ 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. Conclusions: Inosculation of in situ-preformed functional blood vessels represents a promising approach to improve the blood supply to implanted tissue constructs. (Ann Surg 2008;248: 939 -948)
In tissue engineering, rapid ingrowth of blood vessels into scaffolds is a major prerequisite for the survival of three-dimensional tissue constructs. In the present study, we investigated whether the vascularization of implanted poly-D,L-lactic-co-glycolic acid (PLGA) scaffolds may be accelerated by incorporation of Matrigel. For this purpose, we investigated in the aortic ring assay the proangiogenic properties of growth factor reduced Matrigel (GFRM) and growth factor containing Matrigel (GFCM), which were then incorporated into the pores of PLGA scaffolds. Subsequently, we analyzed vascularization, biocompatibility, and incorporation of these scaffolds during 14 days after implantation into dorsal skinfold chambers of balb/c mice by means of intravital microscopy, histology, and immunohistochemistry. Matrigel-free scaffolds served as controls. In the aortic ring assay, GFCM stimulated the development of a network of tubular vessel structures with a significantly increased sprout area and density when compared with GFRM. Accordingly, GFCM accelerated and improved in vivo the ingrowth of new blood vessels into scaffolds, resulting in the formation of a pericyte-coated vascular network with an increased functional capillary density in comparison to the GFRM and control group. Besides, analysis of leukocyte-endothelial cell interaction in host tissue venules located in close vicinity to the scaffolds showed no marked differences in numbers of rolling and adherent leukocytes between the observation groups, indicating that incorporation of Matrigel did not affect biocompatibility of PLGA scaffolds. These findings demonstrate that the combination of proangiogenic extracellular matrices with solid scaffold biomaterials may represent a novel approach to accelerate adequate vascularization of tissue engineering constructs.
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