Aseptic Silk Ligatures Induce Bone Resorption Around Titanium Implants: A 12-Week Pilot Study in Rabbits.

David Reinedahl, Silvia Galli, Tomas Albrektsson, Pentti Tengvall, Ann Wennerberg
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Abstract

Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks).

Materials and methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers.

Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CD11b, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants.

Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress.

无菌蚕丝结扎可诱导钛植入物周围的骨吸收:为期 12 周的兔子试点研究。
目的:口腔种植体周围的边缘骨吸收(MBR)有时可能是一种自限性病症,是由于对所使用材料的免疫反应平衡引起的,而不是进行性细菌感染。与以往结扎诱发实验性种植体周围炎研究的假设相反,我们最近进行的为期 8 周的实验表明,边缘结扎本身会引发炎性免疫反应,导致种植体周围在没有菌斑的情况下发生骨吸收。本研究旨在探讨这种炎症/免疫反应是否会减弱,还是会在更长的愈合时间(12 周)后导致种植失败:在 6 只兔子的钛 (Ti) 种植体顶部放置无菌丝线结扎,并压迫股骨皮质骨板。未结扎的植入体作为对照。浸没愈合 12 周后,用光学显微镜观察种植体和周围组织的切片。还使用选定的 qPCR 标记对边缘软组织进行了分析:从组织学角度看,结扎处被包括多核巨细胞(MNGC)在内的免疫细胞勾勒出轮廓,邻近的纤维包裹和吸收的周边骨与骨结合的非结扎对照种植体形成对比。qPCR 标记物的表达差异不显著,但标记物 CD11b、IL1b、ARG1、NCF1 和 CD4 上调超过 2 倍,CD8 下调超过 2 倍,这表明与对照组相比,结扎引起了轻微的局灶性炎症/免疫反应,M1 和 M2 巨噬细胞、中性粒细胞和辅助性 T 细胞上调,杀伤性 T 细胞下调。此外,与对照组植入物相比,骨形成标志物 OC 和 ALPL 下调了 2 倍以上,这与结扎线缺乏骨结合是一致的:边丝结扎本身会引发口腔种植体周围的炎症/免疫反应和无菌性骨吸收。与我们之前进行的为期 8 周的研究相比,针对丝线的炎症反应似乎随着时间的推移而减弱,只有轻微的炎症持续存在,这可能会阻碍骨结合,转而维持纤维组织包裹型反应。这或许可以解释为什么传统的结扎实验需要定期更换结扎物才能促进骨吸收。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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