Pacheco-Vergara Maria Jesus, Benalcázar-Jalkh Ernesto Byron, Nayak Vasudev V, Bergamo Edmara T P, Cronstein Bruce, Zétola André Luis, Weiss Fernando Pessoa, Grossi João Ricardo Almeida, Deliberador Tatiana Miranda, Coelho Paulo G, Witek Lukasz
Center for Craniofacial Molecular Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA.
Department of Prosthodontic and Periodontology, Bauru School of Dentistry, University of Sao Paulo, Bauru 17012-901, SP, Brazil.
J Funct Biomater. 2023 Jun 1;14(6):308. doi: 10.3390/jfb14060308.
The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (AR), 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.
本研究旨在评估双嘧达莫（一种间接腺苷2A受体（AR））在一个大型的转化性临床前模型中对钛植入物骨整合的影响。将60枚经过酸蚀处理的锥形钛植入物，用四种不同的涂层进行处理（(i) I型牛胶原蛋白（对照），(ii) 10 μM双嘧达莫（DIPY），(iii) 100 μM DIPY，以及(iv) 1000 μM DIPY），植入15只雌性绵羊（体重约65千克）的椎体中。在体内3周、6周和12周后进行定性和定量分析，以评估组织学特征、骨与植入物接触百分比（%BIC）和骨面积分数占有率（%BAFO）。使用一般线性混合模型分析对数据进行分析，将体内时间和涂层作为固定因素。体内3周后的组织形态计量学分析显示，与对照组（17.99% ± 5.82）相比，DIPY涂层植入物组（10 μM（30.42% ± 10.62）、100 μM（36.41% ± 10.62）和1000 μM（32.46% ± 10.62））的%BIC更高。此外，与对照组（31.89% ± 5.46）相比，观察到用1000 μM DIPY增强的植入物的%BAFO显著更高（43.84% ± 9.97）。在6周和12周时，各组之间未观察到显著差异。组织学分析证明所有组的骨整合特征相似，且均为膜内型愈合模式。定性观察证实，在3周时，随着DIPY浓度的增加，与植入物表面紧密接触并在螺纹内的编织骨形成增加。在体内3周时，用双嘧达莫涂覆植入物表面对%BIC和%BAFO产生了有利影响。这些发现表明DIPY对骨整合的早期阶段有积极作用。
