title: Heterogeneity of biomaterial-induced multinucleated giant cells: Possible importance for the regeneration process?
abstract: Biomaterial-associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro- (cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear factor "kappa-light-chain-enhancer" (NF-κB)) and anti-(heme oxygenase-1 (HO-1) and mannose receptor (MR, also known as CD206)). Furthermore, histochemical detection of tartrate-resistant acid phosphatase (TRAP) was conducted to test its predictive efficiency for the pro-inflammatory differentiation of cells. An established system for histomorphometrical analysis was used for counting of BMGCs expressing these molecules. The results show that BMGCs express both pro- and anti-inflammatory molecules within the implantation beds of SF scaffolds in comparable numbers, while only statistically significantly lower numbers of TRAP-positive BMGCs were measured in comparison to the BMGCs expressing the above-mentioned molecules. As these data substantiate the heterogeneity of BMGCs, the question arises to what extent BMGCs can "support" the process of tissue regeneration. Furthermore, the data prompt the question to what extent TRAP-expression within a biomaterial implantation bed can be seen as a predictive marker for an inflammatory condition, as in this study no obvious correlation between TRAP-expression and other pro-inflammatory markers could be observed.
authors.affiliation: Clinic of Oro-Maxillofacial and Plastic Surgery, FORM-Lab, University Medical Center of the Goethe University, Frankfurt, Germany.|Institute of Pathology, REPAIR-Lab, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Barbeck
authors.affiliation: Department of Materials Engineering and Industrial Technologies and BIOtech Research Centre, University of Trento, Trento, I-38050, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Motta
authors.affiliation: Department of Materials Engineering and Industrial Technologies and BIOtech Research Centre, University of Trento, Trento, I-38050, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Migliaresi
authors.affiliation: Clinic of Oro-Maxillofacial and Plastic Surgery, FORM-Lab, University Medical Center of the Goethe University, Frankfurt, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Sader
authors.affiliation: Institute of Pathology, REPAIR-Lab, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Charles James
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.affiliation: Clinic of Oro-Maxillofacial and Plastic Surgery, FORM-Lab, University Medical Center of the Goethe University, Frankfurt, Germany.|Institute of Pathology, REPAIR-Lab, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors.forename: Shahram
authors.initials: S
authors.lastname: Ghanaati
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000009:adverse effects*; D005349:Fibroins / Q000009:adverse effects*; D005549:Foreign-Body Reaction / Q000378:metabolism* / Q000473:pathology; D015743:Giant Cells, Foreign-Body / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008422:Materials Testing; D051379:Mice; D054457:Tissue Scaffolds / Q000009:adverse effects*
chemical_list: D001672:Biocompatible Materials; D018836:Inflammation Mediators; D005349:Fibroins
keywords: biomaterial; foreign body reaction; heterogeneity; inflammation; macrophages; multinucleated giant cells