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Abstract：
The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 μM dipyridamole (DIPY), (iii) 100 μM DIPY, and (iv) 1000 μM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 μM (30.42% ± 10.62), 100 μM (36.41% ± 10.62), and 1000 μM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 μM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration.
摘要：
本研究旨在评估潘生丁的效果，间接腺苷2A受体（A2AR），关于钛植入物的骨整合，转化临床前模型。六十锥形，酸蚀刻钛植入物，用四种不同的涂层处理((i)I型牛胶原蛋白(对照)，（ii）10μM双嘧达莫（DIPY），(iii)100μMDIPY,和(iv)1000μMDIPY)，插入15只雌性绵羊（体重约65公斤）的椎体中。在体内3、6和12周后进行定性和定量分析，以评估组织学特征。骨与植入物接触的百分比(%BIC)和骨面积分数占有率(%BAFO)。使用以体内时间和包衣为固定因子的一般线性混合模型分析来分析数据。体内3周后的组织形态计量学分析显示，DIPY涂层植入物组的BIC较高（10μM（30.42％±10.62），100μM(36.41%±10.62),和1000μM（32.46％±10.62））与对照组（17.99％±5.82）相比。Further,与对照组(31.89%±5.46)相比,用1000μMDIPY增强的植入物观察到显著更高的BAFO(43.84%±9.97).在6周和12周，组间无显著差异.组织学分析表明，所有组的骨整合特征和膜内型愈合模式相似。定性观察证实，随着DIPY浓度的增加，与植入物表面紧密接触的编织骨形成在3周时增加。在体内3周时，用双嘧达莫涂覆植入物表面对BIC和BAFO产生了有利的效果。这些发现表明DIPY对骨整合的早期阶段具有积极作用。
