These authors contributed equally to this study.
Efficient in vivo vascularization of tissue-engineering scaffolds
Article first published online: 23 SEP 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Journal of Tissue Engineering and Regenerative Medicine
Volume 5, Issue 4, pages e52–e62, April 2011
How to Cite
Hegen, A., Blois, A., Tiron, C. E., Hellesøy, M., Micklem, D. R., Nör, J. E., Akslen, L. A. and Lorens, J. B. (2011), Efficient in vivo vascularization of tissue-engineering scaffolds. J Tissue Eng Regen Med, 5: e52–e62. doi: 10.1002/term.336
- Issue published online: 17 MAR 2011
- Article first published online: 23 SEP 2010
- Manuscript Accepted: 20 MAY 2010
- Manuscript Received: 5 MAR 2010
- University of Bergen
- Norwegian Research Council. Grant Numbers: 183850, 183775
- National Institutes of Health. Grant Numbers: P50-CA97248, R21-DE19279
- mural cell;
The success of tissue engineering depends on the rapid and efficient formation of a functional blood vasculature. Adult blood vessels comprise endothelial cells and perivascular mural cells that assemble into patent tubules ensheathed by a basement membrane during angiogenesis. Using individual vessel components, we characterized intra-scaffold microvessel self-assembly efficiency in a physiological in vivo tissue engineering implant context. Primary human microvascular endothelial and vascular smooth muscle cells were seeded at different ratios in poly-L-lactic acid (PLLA) scaffolds enriched with basement membrane proteins (Matrigel) and implanted subcutaneously into immunocompromised mice. Temporal intra-scaffold microvessel formation, anastomosis and perfusion were monitored by immunohistochemical, flow cytometric and in vivo multiphoton fluorescence microscopy analysis. Vascularization in the tissue-engineering context was strongly enhanced in implants seeded with a complete complement of blood vessel components: human microvascular endothelial and vascular smooth muscle cells in vivo assembled a patent microvasculature within Matrigel-enriched PLLA scaffolds that anastomosed with the host circulation during the first week of implantation. Multiphoton fluorescence angiographic analysis of the intra-scaffold microcirculation showed a uniform, branched microvascular network. 3D image reconstruction analysis of human pulmonary artery smooth muscle cell (hPASMC) distribution within vascularized implants was non-random and displayed a preferential perivascular localization. Hence, efficient microvessel self-assembly, anastomosis and establishment of a functional microvasculture in the native hypoxic in vivo tissue engineering context is promoted by providing a complete set of vascular components. Copyright © 2010 John Wiley & Sons, Ltd.