Tendinopathy is a great obstacle in clinical practice due to its poor regenerative capacity. The influence of different stages of tendinopathy on effects of leukocyte-rich platelet-rich plasma (Lr-PRP) has not been elucidated. The aim of this study is to investigate the optimal time point for delivery of Lr-PRP on tendinopathy. A tendinopathy model was established by local collagenase injection on the rabbit Achilles tendon. Then after collagenase induction, following treatments were applied randomly on the lesion: (a) 200 μl of Lr-PRP at 1 week (PRP-1 group), (b) 200 μl of saline at 1 week (Saline-1 group), (c) 200 μl of Lr-PRP at 4 weeks (PRP-2 group), and (d) 200 μl of saline at 4 weeks (Saline-2 group). Six weeks after collagenase induction, outcomes were assessed by magnetic resonance imaging, cytokine quantification, gene expression, histology, and transmission electron microscopy. Our results demonstrated that PRP-1 group had the least cross-sectional area and lesion percent of the involved tendon, as well as the lowest signal intensity in magnetic resonance imaging among all groups. However, the PRP-2 group showed larger cross-sectional area than saline groups. Enzyme-linked immunosorbent assay indicated that PRP-1 group had a higher level of interleukin-10 but lower level of interleukin-6 when compared with PRP-2 and saline groups. Meanwhile, the highest expression of collagen (Col) 1 in PRP-1 and Col 3, matrix metalloproteinase (MMP)-1, and MMP-3 in PRP-2 was found. Histologically, the PRP-1 showed better general scores than PRP-2, and no significant difference was found between the PRP-2 and saline groups. For transmission electron microscopy, PRP-1 had the largest mean collagen fibril diameter, and the PRP-2 group showed even smaller mean collagen fibril diameter than saline groups. In conclusion, intratendon delivery of Lr-PRP at early stage showed beneficial effect for repair of tendinopathy but not at late stage. For translation of our results to clinical circumstances, further studies are still needed.

中文翻译：

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早期肌腱内输送富含白细胞的富含血小板的血浆可促进兔跟腱病模型中的肌腱修复。

肌腱病再生能力差，是临床实践中的一大障碍。肌腱病的不同阶段对富含白细胞的富含血小板的血浆 (Lr-PRP) 的影响尚未阐明。本研究的目的是研究在肌腱病中使用 Lr-PRP 的最佳时间点。通过在兔跟腱上局部注射胶原酶建立肌腱病模型。然后在胶原酶诱导后，在病变上随机应用以下处理：（a）第 1 周 200 μl Lr-PRP（PRP-1 组），（b）第 1 周 200 μl 生理盐水（Saline-1 组）， (c) 4 周时 200 μl Lr-PRP（PRP-2 组），和（d）4 周时 200 μl 盐水（Saline-2 组）。胶原酶诱导后六周，通过磁共振成像、细胞因子定量、基因表达、组织学和透射电子显微镜。我们的结果表明，PRP-1组受累肌腱的横截面积和病变百分比最小，磁共振成像信号强度最低。然而，PRP-2 组显示出比生理盐水组更大的横截面积。酶联免疫吸附试验表明，与PRP-2和生理盐水组相比，PRP-1组的IL-10水平较高，而IL-6水平较低。同时，发现胶原蛋白 (Col) 1 在 PRP-1 和 Col 3、基质金属蛋白酶 (MMP)-1 和 MMP-3 在 PRP-2 中的表达最高。组织学上，PRP-1 显示出比 PRP-2 更好的一般评分，并且 PRP-2 和生理盐水组之间没有发现显着差异。对于透射电子显微镜，PRP-1 的平均胶原纤维直径最大，而 PRP-2 组的平均胶原纤维直径甚至比生理盐水组更小。综上所述，Lr-PRP 在早期肌腱内递送对肌腱病的修复显示出有益效果，但在后期则无。为了将我们的结果转化为临床情况，仍需要进一步的研究。