Artikel
Promoting external inosculation of prevascularized tissue constructs by pre-cultivation in an angiogenic extracellular matrix
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Veröffentlicht: | 20. Mai 2011 |
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Gliederung
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Introduction: The engineering of preformed microvessels offers the promising opportunity to rapidly vascularize implanted tissue constructs by the process of inosculation. Herein, we analyzed whether this process may further be accelerated and improved by cultivation of prevascularized tissue constructs in Matrigel before implantation.
Materials and methods: Nano-size hydroxyapatite particles/poly(ester-urethane) scaffolds (3x3x1mm; n=23) were implanted for 20 days into the flank of 6 FVB/N-TgN (Tie2/GFP) 287 Sato mice to allow the ingrowth of a granulation tissue with green fluorescent protein (GFP)-positive blood vessels. After harvesting, these prevascularized constructs were then transferred into dorsal skinfold chambers of FVB/N recipient mice to study the process of inosculation by means of intravital fluorescence microscopy and immunohistochemistry over 2 weeks. The constructs were implanted directly after embedding in Matrigel (n=7) or after 3 days of cultivation in the extracellular matrix (n=8). Matrigel-free constructs served as control (n=8).
Results: Cultivation in Matrigel resulted in the outgrowth of CD31/GFP-positive vascular sprouts. Vascularization of these constructs was markedly improved when compared to the other two groups, as indicated by a significantly elevated functional microvessel density at day 14 (301±7cm/cm² vs. control: 128±8cm/cm²; p<0.05) after implantation into the dorsal skinfold chamber. This was associated with an increased number of GFP-positive blood vessels (36±6% vs. control: 9±5%; p<0.05) growing into the surrounding host tissue.
Conclusion: The blood supply to prevascularized tissue constructs can be markedly improved by their pre-cultivation in an angiogenic extracellular matrix, promoting external inosculation of the preformed microvascular networks with the host microvasculature.