Laboratory for Applied Periodontal & Craniofacial Regeneration, Department of Periodontics & Oral Biology, Medical College of Georgia School of Dentistry, Augusta, GA 30912, USA.
J Clin Periodontol. 2010 Aug 1;37(8):759-68. doi: 10.1111/j.1600-051X.2010.01579.x. Epub 2010 May 25.
In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge.
Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 microg rhGDF-5, and six animals received implants coated with 120 microg rhGDF-5 or left uncoated (control). Treatments were alternated between jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7, and 8 post-surgery when they were euthanized for histologic evaluation.
The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (+/-SD) 1.6+/-0.6 mm for implants coated with 120 microg rhGDF-5 versus 1.2+/-0.5, 1.2+/-0.6, and 0.6+/-0.2 mm for implants coated with 60 microg rhGDF-5, 30 microg rhGDF-5, or left uncoated, respectively (p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3-4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 microg dose exhibiting more advanced remodelling than the 60 and 30 microg doses. All treatment groups exhibited clinically relevant osseointegration.
rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects.
体外和体内临床前研究表明生长/分化因子-5(GDF-5)可能诱导局部骨形成。本研究的目的是评估涂有重组人 GDF-5(rhGDF-5)的口腔种植体的潜力,该种植体具有特定设计的钛多孔氧化表面,可刺激局部骨形成,包括骨整合和牙槽嵴的垂直增强。
在 12 只年轻的成年猎犬杂种犬中创建双侧、临界尺寸为 5 毫米的超上牙槽嵴周围植入物缺损。6 只动物接受了涂有 30 或 60μg rhGDF-5 的植入物治疗,6 只动物接受了涂有 120μg rhGDF-5 的植入物或未涂层(对照)治疗。治疗在颌骨象限之间交替进行。将黏膜骨膜瓣推进、适应并缝合,以淹没植入物进行一期愈合。当动物在手术后 3、4、7 和 8 周接受荧光骨标记物时,它们被处死进行组织学评估。
临床检查显示 rhGDF-5 涂层的植入物之间没有明显的差异。rhGDF-5 涂层和对照植入物的覆盖螺丝和植入物体都可以通过牙槽黏膜看到/触诊。与对照相比,rhGDF-5 涂层的植入物诱导的骨高度略有增加,rhGDF-5 涂层的植入物诱导的骨高度平均(+/-SD)为 1.6+/-0.6mm,而 60μg rhGDF-5、30μg rhGDF-5 和未涂层的植入物分别为 1.2+/-0.5、1.2+/-0.6 和 0.6+/-0.2mm(p<0.05)。骨形成主要位于植入物的舌侧。新形成的骨中广泛存在黄色和橙色荧光标记物,表明新骨在 3-4 周内形成速度较慢。rhGDF-5 涂层的植入物在驻留骨中显示出有限的种植体周围骨重塑;120μg 剂量比 60μg 和 30μg 剂量表现出更先进的重塑。所有治疗组均表现出具有临床意义的骨整合。
rhGDF-5 涂层口腔植入物显示出剂量依赖性的成骨诱导和/或骨传导作用,骨形成显然受益于局部因素。rhGDF-5 的应用似乎是安全的,因为它与有限的,如果有的话,不良反应有关。