Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells

Shahram Ghanaati, Ronald E. Unger, Matthew J. Webber, Mike Barbeck, Carina Orth, Jenny A. Kirkpatrick, Patrick Booms, Antonella Motta, Claudio Migliaresi, Robert A. Sader, C. James Kirkpatrick

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Successful cell-based tissue engineering requires a rapid and thorough vascularization in order to ensure long-term implant survival and tissue integration. The vascularization of a scaffold is a complex process, and is modulated by the presence of transplanted cells, exogenous and endogenous signaling proteins, and the host tissue reaction, among other influencing factors. This paper presents evidence for the significance of pre-seeded osteoblasts for the in vivo vascularization of a biodegradable scaffold. Human osteoblasts, cultured on silk fibroin micronets in vitro, migrated throughout the interconnected pores of the scaffold and produced extensive bone matrix. When these constructs were implanted in SCID mice, a rapid and thorough vascularization of the scaffold by the host blood capillaries occurred. This profound response was not seen for the silk fibroin scaffold alone. Moreover, when the pre-cultivation time of human osteoblasts was reduced from 14 days to only 24 h, the significant effect these cells exerted on vascularization rate in vivo was still detectable. From these studies, we conclude that matrix and soluble factors produced by osteoblasts can serve to instruct host endothelial cells to migrate, proliferate, and initiate the process of scaffold vascularization. This finding represents a potential paradigm shift for the field of tissue engineering, especially in bone, as traditional strategies to enhance scaffold vascularization have focused on endovascular cells and regarded osteoblasts primarily as cell targets for mineralization. In addition, the migration of host macrophages and multinucleated giant cells into the scaffold was also found to influence the vascularization of the biomaterial. Therefore, the robust effect on scaffold vascularization seen by pre-culturing with osteoblasts appears to occur in concert with the pro-angiogenic stimuli arising from host immune cells.

Original languageEnglish
Pages (from-to)8150-8160
Number of pages11
JournalBiomaterials
Volume32
Issue number32
DOIs
StatePublished - Nov 2011
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to thank A. Sartoris und U.Hilbig for their excellent technical assistance. This work was financially supported by grants from the European commission (EXPERTISSUES Contract no.: 500283- 2 ) and the German Federal Ministry of Education and Research (BMBF German-Chinese Cooperation in Regenerative Medicine).

Keywords

  • Angiogenesis
  • Bone tissue engineering
  • Multinucleated giant cells
  • Osteoblasts
  • Silk fibroin

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