Abstract
The physicochemical properties of synthetically produced bone substitute materials (BSM) have a major impact on biocompatibility. This affects bony tissue integration, osteoconduction, as well as the degradation pattern and the correlated inflammatory tissue responses including macrophages and multinucleated giant cells (MNGCs). Thus, influencing factors such as size, special surface morphologies, porosity, and interconnectivity have been the subject of extensive research. In the present publication, the influence of the granule size of three identically manufactured bone substitute granules based on the technology of hydroxyapatite (HA)-forming calcium phosphate cements were investigated, which includes the inflammatory response in the surrounding tissue and especially the induction of MNGCs (as a parameter of the material degradation). For the in vivo study, granules of three different size ranges (small = 0.355–0.5 mm; medium = 0.5–1 mm; big = 1–2 mm) were implanted in the subcutaneous connective tissue of 45 male BALB/c mice. At 10, 30, and 60 days post implantationem, the materials were explanted and histologically processed. The defect areas were initially examined histopathologically. Furthermore, pro- and anti-inflammatory macrophages were quantified histomorphometrically after their immunohistochemical detection. The number of MNGCs was quantified as well using a histomorphometrical approach. The results showed a granule size-dependent integration behavior. The surrounding granulation tissue has passivated in the groups of the two bigger granules at 60 days post implantationem including a fibrotic encapsulation, while a granulation tissue was still present in the group of the small granules indicating an ongoing cell-based degradation process. The histomorphometrical analysis showed that the number of proinflammatory macrophages was significantly increased in the small granules at 60 days post implantationem. Similarly, a significant increase of MNGCs was detected in this group at 30 and 60 days post implantationem. Based on these data, it can be concluded that the integration and/or degradation behavior of synthetic bone substitutes can be influenced by granule size.
Highlights
In maxillofacial surgery and dentistry, and in medical fields such as orthopedics or traumatology, so-called bone substitute materials (BSM) are applied to allow for successful bone tissue regeneration
Only a thin cell layer was found at the granule surfaces of the big BSM granules that was mainly consisting of macrophages and multinucleated giant cells (MNGCs), while the intergranular spaces were mainly filled out by fatty tissue (Figure 1H)
This study was conducted to clarify the question whether granule size has an influence onto the induction of macrophage subtypes and MNGC formation
Summary
In maxillofacial surgery and dentistry, and in medical fields such as orthopedics or traumatology, so-called bone substitute materials (BSM) are applied to allow for successful bone tissue regeneration. Thereby, BSM have gained special importance within the last decades as they allow the reconstruction of bone without co-morbidities which are common with autologous grafting [1,2,3]. The heterogeneous group of BSM can initially be divided into natural and synthetic materials. A lot of basic knowledge about the molecular healing pathways mediated by synthetic BSM has been gathered in the last decades, the effects of different material characteristics on (the underlying processes of) bone tissue regeneration are still unclear [1]. It has already been revealed that small BSM granules seem to induce a higher inflammatory tissue response associated with an increased implantation bed vascularization, which is an important factor of bone tissue repair [6]
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