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在大鼠股骨模型中局部递送唑来膦酸盐后骨螺钉固定的时间进程——微观有限元分析

Time course of bone screw fixation following a local delivery of Zoledronate in a rat femoral model - a micro-finite element analysis.

作者信息

Kettenberger Ulrike, Latypova Adeliya, Terrier Alexandre, Pioletti Dominique P

机构信息

Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.

Laboratory of Biomechanical Orthopedics, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Switzerland.

出版信息

J Mech Behav Biomed Mater. 2015 May;45:22-31. doi: 10.1016/j.jmbbm.2015.01.007. Epub 2015 Jan 19.

DOI:10.1016/j.jmbbm.2015.01.007
PMID:25679481
Abstract

A good fixation of osteosynthesis implants is crucial for a successful bone healing but often difficult to achieve in osteoporotic patients. One possible solution to this issue is the local delivery of bisphosphonates in direct proximity to the implants, A critical aspect of this method, that has not yet been well investigated, is the time course of the implant fixation following the drug release. Usual destructive mechanical tests require large numbers of animals to produce meaningful results. Therefore, a micro-finite element (microFE) approach was chosen to analyze implant fixation. In vivo micro computed tomography (microCT) scans were obtained, first weekly and later bi-weekly, after implantation of polymeric screws in the femoral condyles of ovariectomized rats. In one half of the animals, Zoledronate was released from a hydrogel matrix directly in the peri-implant bone stock, the other animals were implanted only with screws as control. The time course of the implant fixation was investigated with linear elastic microFE models that were created based on in vivo microCT scans. The numerical models were validated against experimental pullout-tests measurements in an additional cadaver study. The microFE analysis revealed a significant increase in force at yield of the Zoledronate treated group compared to the control group. The force of the treated group was 28% higher after 17 days of screw implantation, 42% higher after 31 days. The significant difference persisted until the end of the in vivo study at day 58 (p<0.01). The early onset and prolonged duration of the implant anchorage improvement that was found in this study indicates the great potential of Zoledronate-loaded hydrogel for an enhancement of osteosynthesis implant fixation in impaired bone.

摘要

骨合成植入物的良好固定对于成功的骨愈合至关重要,但在骨质疏松患者中往往难以实现。解决这个问题的一个可能方法是在植入物附近局部递送双膦酸盐。这种方法的一个关键方面,即药物释放后植入物固定的时间进程,尚未得到充分研究。通常的破坏性力学测试需要大量动物才能产生有意义的结果。因此,选择了微观有限元(microFE)方法来分析植入物固定情况。在去卵巢大鼠的股骨髁中植入聚合物螺钉后,首先每周,然后每两周进行一次体内微型计算机断层扫描(microCT)。在一半的动物中,唑来膦酸从水凝胶基质中直接释放到植入物周围的骨组织中,另一半动物只植入螺钉作为对照。使用基于体内microCT扫描创建的线性弹性microFE模型研究植入物固定的时间进程。在另一项尸体研究中,数值模型根据实验拔出试验测量结果进行了验证。微观有限元分析显示,与对照组相比,唑来膦酸治疗组屈服时的力显著增加。在螺钉植入17天后,治疗组的力高出28%,在31天后高出42%。这种显著差异一直持续到体内研究第58天结束(p<0.01)。本研究中发现的植入物锚固改善的早期开始和持续时间延长表明,负载唑来膦酸的水凝胶在改善受损骨中骨合成植入物固定方面具有巨大潜力。

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