Introduction: After implantation of biomaterials, a response characterized by the presence of foreign body giant cells (FBGC) is often observed. These FBGC are known to result from fusion of macrophages [1]. However, little is known about their exact role or how material properties influence their occurrence. Thus, in the present study the FBGC reaction after implantation of membranes from different biodegradable materials and of membranes and electrospun fibre meshes of the same material in rats was investigated.
Materials and Methods: Pieces (5x5 mm) of a cross-linked acellular porcine dermis collagen matrix (NRX) and Permacol™ were implanted into the neck musculature of 24 male Lewis rats. Peri-implant tissue was obtained after 7, 28, 56 and 112 days. Furthermore, 24 rats received pieces (5x5 mm) of membranes and electrospun meshes from poly(L-lactide-co-D/L-lactide) (PLA) with and without plasma-polymerized allylamine (PPAAm). In this group, peri-implant tissue was evaluated after 7, 14 and 56 days. Tissue cryosections were stained with Haematoxylin/Eosin (HE) and immunohistochemically (APAAP) for CD68+ macrophages/ monocytes (ED1; M1-type) and CD163+ macrophages (ED2; M2-type). FBGC were counted and expressed as cells/mm2, and statistical analysis was performed with Mann-Whitney and Wilcoxon test.
Results and Discussion: The number of FBGC was significantly higher for NRX membranes compared Permacol™ after 28 and 56 days and compared to PLA after 56 days. In contrast, no differences were found after 7 and 112 days. This observation was caused either by the material itself and/ or by its structure since NRX membranes are more porous and thicker than Permacol™ [2]. The number of FBGC was significantly higher for PLA meshes with or without PPAAm film in comparison to PLA membranes on all experimental days. Thus, chemical surface modification with PPAAm, resulting in a positively charged amino-group rich film, did not influence the extent of FBGC formation. The number of FBGC for PLA meshes was about 4-fold higher on day 56 compared to day 7. In contrast, no FBGC were found in the peri-implant tissue of PLA membranes. FBGC were CD68+ but CD163-, thus originating from M1-like macrophages rather than M2-like macrophages.
Conclusion: The results demonstrate that the FBGC reaction caused by different biodegradable materials is predominantly influenced by the structure of the implant. This is demonstrated by the ongoing higher FBGC response for electrospun PLA meshes compared to PLA membranes. Their origin from CD68+ macrophages indicates a pro-inflammatory role. A persistently high presence of FBGC should thus be taken into consideration for clinical purposes.
The study was supported by the German state Mecklenburg-Vorpommern (SYNTERO) and the Federal Ministry of Education & Research (Campus PlasmaMed).
References:
[1] Anderson JM et al., Sem. Immunol. 20: 86-100, 2008
[2] Lucke S et al., Biomed. Res. Int. 2015: ID 938059