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.

Biomaterial‐induced multinucleated giant cells express proinflammatory signaling molecules: A histological study in humans

“…MNGCs, similar to their precursors (macrophages), were suggested to be able to polarize to M1 or M2 subtypes and may therefore demonstrate contribution to the biomaterial‐based regeneration process . In this context, an in vivo study evaluated the inflammatory pattern of the MNGCs induced by the subcutaneous implantation of silk fibrion in CD‐1 mice . The results showed that biomaterial‐induced MNGCs exhibited a similar heterogeneity as macrophages; thus, MNGCs expressed M1 signaling molecules (Cox‐2, CCR‐7, and NF‐Kb) and M2 signaling molecules (CD‐206 and HO‐1) .…”

“…In this context, an in vivo study evaluated the inflammatory pattern of the MNGCs induced by the subcutaneous implantation of silk fibrion in CD‐1 mice . The results showed that biomaterial‐induced MNGCs exhibited a similar heterogeneity as macrophages; thus, MNGCs expressed M1 signaling molecules (Cox‐2, CCR‐7, and NF‐Kb) and M2 signaling molecules (CD‐206 and HO‐1) . However, to the best of our knowledge no studies have yet investigated the polarization pattern of MNGCs induced by different biomaterials compared to the physiological inflammatory pattern in non‐augmented bone in human tissue.…”

“…Immunohistochemical staining was performed following the established protocols as previously described . The slides were heated at 60°C for 1 hour before the pretreatment procedures.…”

Reduction of relative centrifugal forces increases growth factor release within solid platelet-rich-fibrin (PRF)-based matrices: a proof of concept of LSCC (low speed centrifugation concept)

“…As previously described [5,16], the PRF clots were collected after 10 days and fixed in Roti ® -Histofix 4%, acid free (pH 7), and 4% phosphate-buffered formaldehyde solution (Carl-Roth) for 24 h. The PRF-based matrices were dehydrated in a series of alcohol and xylene through a Tissue Processor (TP1020, Leica Biosystems Nussloch GmbH, Germany) and embedded in paraffin blocks. Afterwards, 3 µm thick sections from each sample were cut by a rotatory microtome (Leica RM2255, Wetzlar, Germany).…”

Avaliação microtomográfica e histomorfométrica comparativa de levantamento de seio maxilar em coelhos utilizando diferentes cerâmicas a base de fosfato de cálcio

“…Segundo (Barbeck et al, 2016), as CGMs devem ser consideradas como um "sincício funcional" de macrófagos, que reagem similarmente a seus precursores mononucleares frente a um determinado material. (Anderson e Jones, 2007;Jones et al, 2007;Anderson et al, 2008;Ghanaati et al, 2010).…”