title: Scaffold vascularization in vivo driven by primary human osteoblasts in concert with host inflammatory cells.
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.
authors.affiliation: REPAIR-Lab, Institute of Pathology, Johannes Gutenberg University, Langenbeckstrasse. 1, 55101 Mainz, Germany. ghanaati@uni-mainz.de
authors.forename: Shahram
authors.initials: S
authors.lastname: Ghanaati
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.forename: Mike
authors.initials: M
authors.lastname: Barbeck
authors.forename: Carina
authors.initials: C
authors.lastname: Orth
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Kirkpatrick
authors.forename: Patrick
authors.initials: P
authors.lastname: Booms
authors.forename: Antonella
authors.initials: A
authors.lastname: Motta
authors.forename: Claudio
authors.initials: C
authors.lastname: Migliaresi
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sader
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D005349:Fibroins / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D019919:Prosthesis Implantation; D013997:Time Factors; D054457:Tissue Scaffolds / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D005349:Fibroins