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Bevacizumab Improves Achilles Tendon Repair in a Rat Model

机译：贝伐单抗改善大鼠模型中的跟腱修复

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Background/Aims Effective wound-healing generally requires efficient re-vascularization after injury, ensuring sufficient supply with oxygen, nutrients, and various cell populations. While this applies to most tissues, tendons are mostly avascular in nature and harbor relatively few cells, probably contributing to their poor regenerative capacity. Considering the minimal vascularization of healthy tendons, we hypothesize that controlling angiogenesis in early tendon healing is beneficial for repair tissue quality and function. Methods To address this hypothesis, Bevacizumab, a monoclonal antibody blocking VEGF-A signaling, was locally injected into the defect area of a complete tenotomy in rat Achilles tendon. At 28 days post-surgery, the defect region was investigated using immunohistochemistry against vascular and lymphatic epitopes. Polarization microscopy and biomechanical testing was used to determine tendon integrity and gait analysis for functional testing in treated vs non-treated animals. Results Angiogenesis was found to be significantly reduced in the Bevacizumab treated repair tissue, accompanied by significantly reduced cross sectional area, improved matrix organization, increased stiffness and Young’s modulus, maximum load and stress. Further, we observed an improved gait pattern when compared to the vehicle injected control group. Conclusion Based on the results of this study we propose that reducing angiogenesis after tendon injury can improve tendon repair, potentially representing a novel treatment-option.
机译：背景/目的有效的伤口愈合通常需要在受伤后进行有效的血管再生，以确保充足的氧气，营养和各种细胞群。尽管这适用于大多数组织，但肌腱本质上大多是无血管的，并且具有相对较少的细胞，可能是导致其再生能力差的原因。考虑到健康肌腱的最小血管生成，我们假设在肌腱早期愈合中控制血管生成有益于修复组织的质量和功能。方法为了解决这个假设，将贝伐单抗（一种阻断VEGF-A信号转导的单克隆抗体）局部注入大鼠跟腱完全腱切开术的缺损区域。术后28天，使用免疫组织化学针对血管和淋巴表位研究缺损区域。使用偏光显微镜和生物力学测试来确定肌腱完整性和步态分析，以进行治疗和未治疗动物的功能测试。结果发现在贝伐单抗治疗的修复组织中血管生成显着减少，同时横截面积显着减少，基质组织改善，刚度和杨氏模量增加，最大负荷和应力增加。此外，与载药对照组相比，我们观察到步态模式有所改善。结论基于这项研究的结果，我们建议减少肌腱损伤后的血管生成可以改善肌腱修复，可能代表了一种新的治疗选择。

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