State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Oral Implants, School of Stomatology, The Fourth Military Medical University, China.
Department of Stomatology, The 901st Hospital of the Joint Logistics Support Force of PLA, Hefei, China.
J Biomed Mater Res A. 2020 Nov 1;108(11):2206-2216. doi: 10.1002/jbm.a.36978. Epub 2020 Jun 9.
To investigate the role of macrophages in the osseointegration of dental implants through induced macrophage reduction in a murine model. Fifty-four Sprague-Dawley rats with bilateral maxillary first molars replaced by titanium implants were randomly assigned into three groups. For the test group, macrophages were depleted by tail-vein injection of clodronate liposome (20 mg/kg) 3 days before implantation and reinjection every 3 days until the sacrifice of the rats (10 mg/kg). Animals treated with Phosphate Buffer saline (PBS) alone or empty liposome were included as controls. Samples contained implants were retrieved after 3, 7, 14, and 28 days, and the alterations of macrophages (CD68) and osteoblasts (Osterix) were evaluated using histology and immunohistochemistry technique. Histological analysis showed that new bone gradually formed within the lateral chamber regions in both the Control group and the Lip group, whereas bone healing was delayed at the first 2-weeks despite of pronounced newly formed peri-implant bone at 4 weeks in the Lipclod group. The bone-to-implant contact was significantly higher in the Lip and Control group than in the Lipclod group after 2 weeks. Immunohistochemical analysis showed that CD68+ cells were present both in the central region and in direct contact with implant surface throughout the healing period. Macrophages depletion reduced osteoblast amounts and new bone formation around implants in the first 2 weeks, and have no adverse impacts on the final formation of osseointegration. Macrophages play a dual role in both regulating the bone healing process and immune response to implant installation during the early stages.
为了研究巨噬细胞在牙种植体骨整合中的作用，通过在小鼠模型中诱导巨噬细胞减少来研究。将 54 只双侧上颌第一磨牙缺失的 Sprague-Dawley 大鼠随机分为三组。实验组在种植前 3 天通过尾静脉注射氯膦酸盐脂质体（20mg/kg），并在第 3 天至第 14 天每 3 天注射一次，直到处死大鼠（10mg/kg）。单独用磷酸盐缓冲盐水（PBS）或空脂质体处理的动物作为对照。植入物含有样本在植入后 3、7、14 和 28 天取出，并用组织学和免疫组织化学技术评估巨噬细胞（CD68）和成骨细胞（Osterix）的变化。组织学分析显示，在对照组和脂质体组中，新骨逐渐在侧室区域形成，而在脂质体氯膦酸盐组中，尽管在第 4 周有明显的新形成的种植体周围骨，但在前 2 周骨愈合延迟。在第 2 周后，脂质体和对照组的骨-种植体接触明显高于脂质体氯膦酸盐组。免疫组织化学分析显示，在整个愈合期，CD68+细胞存在于中央区域，并与植入物表面直接接触。巨噬细胞耗竭减少了前 2 周内植入物周围的成骨细胞数量和新骨形成，但对最终骨整合的形成没有不良影响。巨噬细胞在调节骨愈合过程和对植入物安装的免疫反应方面发挥双重作用，特别是在早期阶段。
