title: Influence of β-tricalcium phosphate granule size and morphology on tissue reaction in vivo.
abstract: In this study the tissue reaction to five different β-tricalcium phosphate (β-TCP)-based bone substitute materials differing only in size, shape and porosity was analyzed over 60 days, at 3, 10, 15, 30 and 60 days after implantation. Using the subcutaneous implantation model in Wistar rats both the inflammatory response within the implantation bed and the resulting vascularization of the biomaterials were qualitatively and quantitatively assessed by means of standard and special histological staining methods. The data from this study showed that all investigated β-TCP bone substitutes induced the formation of multinucleated giant cells. Changes in size, shape and porosity influenced the integration of the biomaterials within the implantation bed and the formation of tartrate-resistant acid phosphatase (TRAP)-positive and TRAP-negative multinucleated giant cells, as well as the rate of vascularization. While a high porosity generally allowed cell and fiber in-growth within the center of the bone substitute, a lower porosity resulted in a mosaic-like integration of the materials, with the granules serving as place holders. The number of multinucleated giant cells located in the implantation bed positively correlated with the vascularization rate. These data emphasize that all biomaterials investigated were capable of inducing the formation of TRAP-positive multinucleated giant cells as a sign of biomaterial stability. Furthermore, these cells directly influenced vascularization by secretion of vascular endothelial growth factor (VEGF), as well as other chemokines. Based on these findings, the role of multinucleated giant cells in the foreign body reaction to biomaterials might need to be reconsidered. This study demonstrates that variations in the physical properties of a bone substitute material clearly influence the (extent of the) inflammatory reaction and its consequences.
authors.affiliation: Institute of Pathology, REPAIR Laboratory, Johannes Gutenberg University Mainz, 55101 Mainz, Germany. ghanaati@uni-mainz.de
authors.forename: Shahram
authors.initials: S
authors.lastname: Ghanaati
authors.forename: Mike
authors.initials: M
authors.lastname: Barbeck
authors.forename: Carina
authors.initials: C
authors.lastname: Orth
authors.forename: Ines
authors.initials: I
authors.lastname: Willershausen
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Thimm
authors.forename: Christiane
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Angela
authors.initials: A
authors.lastname: Rasic
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sader
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Unger
authors.forename: Fabian
authors.initials: F
authors.lastname: Peters
authors.forename: C James
authors.initials: CJ
authors.lastname: Kirkpatrick
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D018786:Bone Substitutes / Q000494:pharmacology; D002130:Calcium Phosphates / Q000737:chemistry* / Q000494:pharmacology*; D015726:Giant Cells / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009928:Organ Specificity / Q000187:drug effects*; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D002130:Calcium Phosphates; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate