Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
Department of Oral and Craniomaxillofacial Surgery, Faculty of Medicine, Medical Center-University of Freiburg, Freiburg, Germany.
J Dent Res. 2020 Jul;99(8):930-937. doi: 10.1177/0022034520917903. Epub 2020 May 8.
Tooth extraction results in alveolar bone resorption and is accompanied by postoperative swelling and pain. Maresin 1 (MaR1) is a proresolving lipid mediator produced by macrophages during the resolution phase of inflammation, bridging healing and tissue regeneration. The aim of this study was to examine the effects of MaR1 on tooth extraction socket wound healing in a preclinical rat model. The maxillary right first molars of Sprague-Dawley rats were extracted, and gelatin scaffolds were placed into the sockets with or without MaR1. Topical application was also given twice a week until complete socket wound closure up to 14 d. Immediate postoperative pain was assessed by 3 scores. Histology and microcomputed tomography were used to assess socket bone fill and alveolar ridge dimensional changes at selected dates. The assessments of coded specimens were performed by masked, calibrated examiners. Local application of MaR1 potently accelerated extraction socket healing. Macroscopic and histologic analysis revealed a reduced soft tissue wound opening and more rapid re-epithelialization with MaR1 delivery versus vehicle on socket healing. Under micro-computed tomography analysis, MaR1 (especially at 0.05 μg/μL) stimulated greater socket bone fill at day 10 as compared with the vehicle-treated animals, resulting in less buccal plate resorption and a wider alveolar ridge by day 21. Interestingly, an increased ratio of CD206:CD68 macrophages was identified in the sockets with MaR1 application under immunohistochemistry and immunofluorescence analysis. As compared with the vehicle therapy, local delivery of MaR1 reduced immediate postoperative surrogate pain score panels. In summary, MaR1 accelerated extraction wound healing, promoted socket bone fill, preserved alveolar ridge bone, and reduced postoperative pain in vivo with a rodent preclinical model. Local administration of MaR1 offers clinical potential to accelerate extraction socket wound healing for more predictable dental implant reconstruction.
拔牙会导致牙槽骨吸收，并伴有术后肿胀和疼痛。maresin 1（MaR1）是巨噬细胞在炎症消退阶段产生的一种促解决脂质介质，可促进愈合和组织再生。本研究旨在通过临床前大鼠模型研究 MaR1 对拔牙窝愈合的影响。拔除 Sprague-Dawley 大鼠右上颌第一磨牙，将明胶支架放入牙槽窝中，有无 MaR1。每周两次局部应用，直至完全闭合拔牙窝，最长 14 天。术后即刻疼痛采用 3 分制评估。组织学和微计算机断层扫描用于评估选定日期的牙槽骨填充和牙槽嵴尺寸变化。对编码标本的评估由盲法、校准的检查者进行。局部应用 MaR1 可强力加速拔牙窝愈合。宏观和组织学分析显示，与载体相比，MaR1 给药时软组织伤口开口减小，再上皮化更快。在微计算机断层扫描分析中，与载体处理的动物相比，MaR1（尤其是 0.05μg/μL）在第 10 天刺激更大的牙槽骨填充，导致第 21 天颊板吸收减少和牙槽嵴更宽。有趣的是，在免疫组织化学和免疫荧光分析中，发现 MaR1 应用的牙槽窝中 CD206：CD68 巨噬细胞的比例增加。与载体治疗相比，MaR1 局部给药可减少术后即刻替代疼痛评分。总之，MaR1 加速了拔牙伤口愈合，促进了牙槽骨填充，保存了牙槽嵴骨，并减少了体内啮齿动物临床前模型的术后疼痛。MaR1 的局部给药为加速拔牙窝愈合提供了临床潜力，以实现更可预测的牙种植体重建。
