Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model

Abstract

Background: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. Purpose: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Study Design: Controlled laboratory study. Methods: Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). Results: MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP (P = .001) and saline (P < .001) groups. Additionally, TEM showed that the Lp-PRP group had larger collagen fibril diameters than the Lr-PRP group (P < .001). Enzyme-linked immunosorbent assay showed a significantly lower level of catabolic cytokine IL-6 in the Lp-PRP group compared with the Lr-PRP (P = .001) and saline (P = .021) groups. The Lp-PRP group displayed significantly increased expression of collagen I compared with the saline group (P = .004) but not the Lr-PRP group. Both the Lp-PRP and Lr-PRP groups exhibited significantly lower matrix metalloproteinase (MMP)–1 and MMP-3 expression levels compared with the saline group. However, only the Lp-PRP group displayed significantly higher expression of TIMP-1 than the saline group (P = .024). Conclusion: Compared with Lr-PRP, Lp-PRP improves tendon healing and is a preferable option for the clinical treatment of tendinopathy. Clinical Relevance: PRP is widely used in the clinical management of chronic tendinopathy. However, the clinical results are ambiguous. It is imperative to understand the influence of leukocytes on PRP-mediated tissue healing in vivo, which could facilitate the better clinical management of chronic tendinopathy. Further studies are needed to translate our findings to the clinical setting.