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Investigation of Sustained BMP Delivery in the Prevention of Medication-Related Osteonecrosis of the Jaw (MRONJ) in a Rat Model.
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2019-09-24 , DOI: 10.1002/mabi.201900226
Gary I Brierly 1, 2 , Jiongyu Ren 1, 3 , Jeremy Baldwin 1, 3 , Siamak Saifzadeh 1, 3 , Christina Theodoropoulos 1, 3 , Mikhail V Tsurkan 1, 4 , Anthony Lynham 1, 3 , Edward Hsu 1, 2 , Dimitrios Nikolarakos 1, 5 , Carsten Werner 4, 6 , Maria A Woodruff 1, 3 , Dietmar W Hutmacher 1, 3 , Laura J Bray 1, 3, 4
Affiliation  

Medication‐related osteonecrosis of the jaw (MRONJ) poses an ongoing challenge for clinicians and researchers. Currently, there is a lack of preventative measures available for at‐risk patients undergoing tooth extractions, especially those with prior bisphosphonate treatment due to osteoporosis or bone metastasis diagnoses. Here, these issues are addressed using a preventative tissue engineering strategy against MRONJ development. This study evaluates the efficacy of a poly(ethylene glycol)‐heparin hydrogel as a tool for the delivery of arginylglycylaspartic acid (RGD) and recombinant human bone morphogenic protein‐2 (rhBMP‐2). Three groups of skeletally mature rats each receive two doses of intravenous zoledronic acid prior to surgery and undergo extraction of the right first mandibular molar with gingival closure. Experimental groups either have the sockets left empty, filled with hydrogel minus rhBMP‐2, or filled with hydrogel plus rhBMP‐2. Eight weeks postoperatively specimens are analyzed using radiological, histological, and scanning electron microscopy (SEM) techniques. µCT analysis shows increased bone formation with hydrogel/rhBMP‐2 delivery compared to the empty socket. Hydrogel‐treated groups display increased presence of osteocytes and increased osteoclastic action compared to the empty sockets. These results represent the first step toward improved delivery of rhBMP‐2 and a potential MRONJ preventative for patients undergoing bisphosphonate treatment.

中文翻译:

持续BMP输送在预防大鼠模型中与药物相关的下颌骨坏死(MRONJ)方面的研究。

与药物有关的颌骨坏死(MRONJ)对临床医生和研究人员构成了持续的挑战。当前,对于正在拔牙的高危患者,尤其是由于骨质疏松或骨转移诊断而接受过双膦酸盐治疗的患者,目前尚缺乏预防措施。在这里,使用针对MRONJ的预防性组织工程策略解决了这些问题。这项研究评估了聚乙二醇-肝素水凝胶作为递送精氨酰糖基天冬氨酸(RGD)和重组人骨形态发生蛋白2(rhBMP-2)的工具的功效。三组骨骼成熟的大鼠在手术前分别接受两剂静脉注射唑来膦酸,并取出右下颌第一磨牙并关闭牙龈。实验组要么让插座空着,要么装满水凝胶减去rhBMP-2,要么装满水凝胶加上rhBMP-2。术后八周使用放射学,组织学和扫描电子显微镜(SEM)技术分析标本。µCT分析显示,与空牙槽相比,水凝胶/ rhBMP-2递送增加了骨形成。与空牙槽相比,水凝胶治疗组的骨细胞增加,破骨作用增加。这些结果代表了改善rhBMP-2递送的第一步,也是接受双膦酸盐治疗的患者潜在的MRONJ预防剂。和扫描电子显微镜(SEM)技术。µCT分析显示,与空牙槽相比,水凝胶/ rhBMP-2递送增加了骨形成。与空牙槽相比,水凝胶治疗组的骨细胞增加,破骨作用增加。这些结果代表了改善rhBMP-2递送的第一步,也是接受双膦酸盐治疗的患者潜在的MRONJ预防剂。和扫描电子显微镜(SEM)技术。µCT分析显示,与空牙槽相比,水凝胶/ rhBMP-2递送增加了骨形成。与空牙槽相比,水凝胶治疗组的骨细胞增加,破骨作用增加。这些结果代表了改善rhBMP-2递送的第一步,也是接受双膦酸盐治疗的患者潜在的MRONJ预防剂。
更新日期:2019-09-24
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