Abstract
Multinucleated giant cells (MNGCs) are frequently observed in the implantation areas of different biomaterials. The main aim of the present study was to analyze the long-term polarization pattern of the pro- and anti-inflammatory phenotypes of macrophages and MNGCs for 180 days to better understand their role in the success or failure of biomaterials. For this purpose, silk fibroin (SF) was implanted in a subcutaneous implantation model of Wistar rats as a model for biomaterial-induced MNGCs. A sham operation was used as a control for physiological wound healing. The expression of different inflammatory markers (proinflammatory M1: CCR-7, iNos; anti-inflammatory M2: CD-206, CD-163) and tartrate-resistant acid phosphatase (TRAP) and CD-68 were identified using immunohistochemical staining. The results showed significantly higher numbers of macrophages and MNGCs within the implantation bed of SF-expressed M1 markers, compared to M2 markers. Interestingly, the expression of proinflammatory markers was sustained over the long observation period of 180 days. By contrast, the control group showed a peak of M1 macrophages only on day 3. Thereafter, the inflammatory pattern shifted to M2 macrophages. No MNGCs were observed in the control group. To the best of our knowledge, this is study is the first to outline the persistence of pro-inflammatory MNGCs within the implantation bed of SF and to describe their long-term kinetics over 180 days. Clinically, these results are highly relevant to understand the role of biomaterial-induced MNGCs in the long term. These findings suggest that tailored physicochemical properties may be a key to avoiding extensive inflammatory reactions and achieving clinical success. Therefore, further research is needed to elucidate the correlation between proinflammatory MNGCs and the physicochemical characteristics of the implanted biomaterial.
Highlights
A wide variety of biomaterials are available for clinical applications in different fields to support both soft and bone tissue regeneration [1,2]
We have shown that silk fibroin treated with formic acid for 60 min induced a higher number of multinucleated giant cells (MNGCs) compared to SF treated with formic acid for 30 min [28]
The present study showed that the SF-induced MNGCs studied here express proinflammatory molecules such as inducible nitric oxide synthase (iNOS) and CCR-7 rather than anti-inflammatory molecules such as CD-206
Summary
A wide variety of biomaterials are available for clinical applications in different fields to support both soft and bone tissue regeneration [1,2]. Different natural polymers have been widely investigated and developed for use as biomaterials, including collagen [4], chitosan [5], alginate [6], and silk [1]. Their large availability and biocompatibility make them an important source of materials that can be applied to replace damaged tissue in many fields. Other studies implemented SF in combination with collagen to develop a 3D bioprintable material with reinforced mechanical properties [9]
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