The host macrophage response to implants has shown to be affected by tissue location and physio-pathological conditions of the patient. Success in immunomodulatory strategies is thus predicated on the proper understanding of the macrophage populations participating on each one of these contexts. The present study uses an in vivo implantation model to analyze how immunomodulation via an IL-4 eluting implant affects distinct macrophage populations at the tissue-implant interface and how this may affect downstream regenerative processes. Populations identified as F4/80⁺, CD68⁺ and CD11b⁺ macrophages at the peri-implant space showed distinct susceptibility to polarize towards an M2-like phenotype under the effects of delivered IL-4. Also, the presence of the coating resulted in a significant reduction in F4/80⁺ macrophages, while other populations remained unchanged. These results suggests that the F4/80⁺ macrophage population may be predominant in the early stages of the host response at the surface of these implants, in contrast to CD11b⁺ macrophage populations which were either fewer in number or located more distant from the implant surface. Gene expression assays showed increased proteolytic activity and diminished matrix deposition as possible mechanisms explaining the decreased fibrotic capsule deposition and improved peri-implant tissue quality shown in previous studies using IL-4 eluting coatings. The pattern of M2-like gene expression promoted by IL-4 was correlated with glycosaminoglycan production within the site of implantation at early stages of the host response, suggesting a significant role in this response. These findings demonstrate that immunomodulatory strategies can be utilized to design and implement targeted delivery for improving biomaterial performance.

中文翻译：

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与宿主植入物界面处的 IL-4 介导的免疫调节相关的不同巨噬细胞群和表型。

宿主巨噬细胞对植入物的反应已被证明受到患者组织位置和生理病理状况的影响。因此，免疫调节策略的成功取决于对参与其中每一种情况的巨噬细胞群的正确理解。本研究使用体内植入模型来分析通过IL-4 洗脱植入物进行的免疫调节如何影响组织-植入物界面上不同的巨噬细胞群，以及这如何影响下游的再生过程。种植体周围空间被鉴定为F4/80 ⁺、CD68 ⁺和CD11b ⁺巨噬细胞的群体在递送的IL-4的作用下表现出向M2样表型极化的明显易感性。此外，涂层的存在导致 F4/80 ⁺巨噬细胞显着减少，而其他群体保持不变。这些结果表明，F4/80 ⁺巨噬细胞群可能在这些植入物表面宿主反应的早期阶段占主导地位，而 CD11b ⁺巨噬细胞群则数量较少或距离植入物表面较远。 。基因表达测定显示蛋白水解活性增加和基质沉积减少，这可能是解释纤维化囊沉积减少和种植体周围组织质量改善的可能机制，这在之前使用IL-4洗脱涂层的研究中显示。IL-4 促进的 M2 样基因表达模式与宿主反应早期植入位点内的糖胺聚糖产生相关，表明在这种反应中发挥着重要作用。这些发现表明，免疫调节策略可用于设计和实施靶向递送，以改善生物材料的性能。