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局部递送重组肝细胞生长因子促进兔肌腱-骨愈合。

Facilitated tendon-bone healing by local delivery of recombinant hepatocyte growth factor in rabbits.

机构信息

Department of Orthopaedic Surgery, School of Medicine, Kanazawa University, Kanazawa, Japan.

出版信息

Arthroscopy. 2010 Jan;26(1):84-90. doi: 10.1016/j.arthro.2009.06.029.

DOI:10.1016/j.arthro.2009.06.029
PMID:20117631
Abstract

PURPOSE

This study was performed to evaluate the therapeutic effect of hepatocyte growth factor (HGF) on tendon-bone healing in a rabbit model.

METHODS

In adult rabbits the long digital extensor tendon was detached from the lateral femoral condyle, and the free end of the tendon was inserted into a tunnel drilled into the proximal tibial metaphysis. Cancellous bone obtained during drilling of the tibial hole was soaked in saline solution or solution containing 100-microg/mL human recombinant HGF and then transplanted into the bone tunnel. Junctional healing between the tendon and the bone was evaluated by histologic analysis and uniaxial load-to-failure testing at 2, 4, 6, 8, and 12 weeks after surgery.

RESULTS

In the saline solution-treated control group, Sharpey-like fibers, which connected the tendon graft and the bone tissue, appeared 6 weeks after treatment. At 8 weeks after treatment, maturation of lamellar bone was seen, and at 12 weeks, the adhesion between tendon and bone appeared to be supported by indirect insertion of fibrocartilaginous tissue, wherein the border between the fibrocartilaginous tissue and tendon or bone was significant. In the HGF-treated group, the fibrous tissues were parallel to the load axis, and lamellar bone and Sharpey-like fibers appeared as early as 4 weeks after treatment. At 12 weeks, junctional tissue, characterized by a continuous 4-layer structure of bone, calcified cartilage, fibrocartilage, and tendon, was regenerated by a direct insertion. On biomechanical testing, the HGF-treated group had significantly better biomechanical properties than the control group at 2 and 4 weeks. The histologic improvement caused by HGF treatment was associated with the biomechanical improvement.

CONCLUSIONS

Local administration of recombinant HGF promotes the adhesive healing process at the tendon-bone junction, both histologically and mechanically, after ligament reconstruction in a rabbit model.

CLINICAL RELEVANCE

Application of HGF may be considered as a new therapeutic approach to accelerate healing and rehabilitation after ligament reconstruction.

摘要

目的

本研究旨在评估肝细胞生长因子(HGF)在兔模型中对腱骨愈合的治疗效果。

方法

在成年兔中,将长指伸肌腱从外侧股骨髁上剥离,将肌腱游离端插入钻入近侧胫骨干骺端的隧道中。在胫骨钻孔过程中获得的松质骨用生理盐水或含有 100μg/ml 人重组 HGF 的溶液浸泡,然后移植到骨隧道中。术后 2、4、6、8 和 12 周时,通过组织学分析和单轴加载至失效试验评估腱骨交界处的愈合情况。

结果

在生理盐水处理的对照组中,治疗后 6 周出现了类似于Sharpey 的纤维,将肌腱移植物与骨组织连接起来。治疗后 8 周可见板层骨成熟,治疗后 12 周,肌腱与骨之间的粘连似乎由纤维软骨组织的间接插入所支撑,其中纤维软骨组织与肌腱或骨之间的边界明显。在 HGF 治疗组中,纤维组织与载荷轴平行,早在治疗后 4 周就出现了板层骨和类似于Sharpey 的纤维。治疗后 12 周,腱骨交界处再生的组织具有连续的 4 层结构,包括骨、钙化软骨、纤维软骨和肌腱。生物力学测试结果显示,HGF 治疗组在治疗后 2 周和 4 周的生物力学性能明显优于对照组。HGF 治疗引起的组织学改善与生物力学改善相关。

结论

局部给予重组 HGF 可促进兔模型中韧带重建后腱骨交界处的黏附愈合过程,在组织学和力学上均有改善。

临床相关性

HGF 的应用可能被认为是一种加速韧带重建后愈合和康复的新治疗方法。

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