Int J Oral Maxillofac Implants. 2023 Dec 12;38(6):1200-1210. doi: 10.11607/jomi.10335.
To analyze the process of early oral osseointegration of titanium (Ti) implants in diabetic 129/Sv mice through microCT and histologic and immunohistochemical analysis.
A group of 30 male 129/Sv mice was equally subdivided into two groups: (1) nondiabetic (ND), in which mice did not undergo systemic alterations and received a standard diet, and (2) diabetic (D), in which mice were provided a high-fat diet from the age of 6 weeks until the conclusion of the study and received two intraperitoneal (IP) injections of streptozotocin (STZ) at a concentration of 100 mg/Kg each. Each mouse underwent extraction of a maxillary first molar, and customized Ti screws (0.50 mm diameter, 1.5 mm length) were placed in the residual alveolar sockets of the palatal roots. At 7 and 21 days after implant placement, the animals were euthanized for maxilla and pancreas collection. Maxillae containing Ti implants were analyzed with microCT, histology, and immunohistochemistry for cells that were positive for F4/80, CD146, runt-related transcription factor 2 (Runx2), and proliferating cell nuclear antigen (PCNA). Pancreata were histologically analyzed. Quantitative data were statistically analyzed with a significance level at 5% (P < .05).
ND mice presented successful healing and osseointegration, with a significantly higher fraction of bone volume compared to D mice, both at the alveolar sockets (53.39 ± 5.93 and 46.08 ± 3.18, respectively) and at the implant sites (68.88 ± 7.07 and 44.40 ± 6.98, respectively) 21 days after implant placement. Histologic evaluation revealed that the ND mice showed a significant decrease in inflammatory infiltrate and a significant increase in newly formed bone matrix at 21 days, whereas peri-implant sites in the D mice were predominantly encapsulated by fibrous tissue and chronic inflammatory infiltrate. Immunohistochemical characterization revealed higher Runx2 osteoblast differentiation and higher cell proliferation activity in the ND mice at 7 days, while higher amounts of macrophages were present in D mice at 7 and 21 days. Interestingly, no differences were found in CD146-positive cells when comparing ND and D mice.
This study evaluated the effects of immediate dental implant placement in 129/Sv diabetic mice by using specific healing markers to identify changes in cellular events involved in early oral osseointegration. This approach may serve as tool to evaluate new materials and surface coatings to improve osseointegration in diabetic patients.
通过微 CT 及组织学和免疫组织化学分析,研究糖尿病 129/Sv 小鼠钛(Ti)种植体早期口腔骨整合的过程。
将 30 只雄性 129/Sv 小鼠等分为两组:(1)非糖尿病(ND)组,小鼠未发生全身改变,给予标准饮食;(2)糖尿病(D)组,小鼠从 6 周龄开始给予高脂肪饮食,直至研究结束,同时给予两次腹腔内(IP)链脲佐菌素(STZ)注射,浓度为 100mg/Kg。每只小鼠均行上颌第一磨牙拔除术,在腭根残留牙槽窝内植入定制 Ti 螺钉(直径 0.50mm,长 1.5mm)。种植体植入后 7 和 21 天,处死动物取上颌骨和胰腺。对含有 Ti 种植体的上颌骨进行微 CT、组织学和免疫组织化学分析,检测 F4/80、CD146、成骨相关转录因子 2(Runx2)和增殖细胞核抗原(PCNA)阳性细胞。对胰腺进行组织学分析。采用统计学方法分析定量数据,显著性水平为 5%(P<0.05)。
ND 组小鼠愈合和骨整合成功,与 D 组相比,牙槽窝(分别为 53.39±5.93 和 46.08±3.18)和种植体部位(分别为 68.88±7.07 和 44.40±6.98)的骨体积分数明显更高,均在种植体植入后 21 天。组织学评价显示,ND 组小鼠在第 21 天炎症浸润明显减少,新形成的骨基质明显增加,而 D 组小鼠种植体周围主要被纤维组织和慢性炎症浸润包裹。免疫组织化学特征显示,ND 组小鼠在第 7 天 Runx2 成骨分化和细胞增殖活性较高,而 D 组小鼠在第 7 和 21 天巨噬细胞较多。有趣的是,比较 ND 组和 D 组时,CD146 阳性细胞无差异。
本研究通过使用特定的愈合标志物评估了即刻牙种植在 129/Sv 糖尿病小鼠中的效果,以确定早期口腔骨整合过程中细胞事件的变化。这种方法可作为评估新的材料和表面涂层以改善糖尿病患者骨整合的工具。