Intratendon delivery of leukocyte‐rich platelet‐rich plasma at early stage promotes tendon repair in a rabbit Achilles tendinopathy model

Abstract

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.

Effects of leukocyte‑ and platelet‑rich plasma on tendon disorders based on in vitro and in vivo studies (Review)

“…Therefore, whether inflammation is beneficial for tendon healing depends on the different stages of tendon disorders. A previous study demonstrated that delivery of L-PRP at the early rather than the late stage promoted the repair of Achilles tendinopathy in rabbits and suggested that L-PRP may alleviate inflammation at the early stage, whereas L-PRP exerted a less prominent beneficial effect at the late stage of tendinopathy (23). This is consistent with the findings of Zhang et al (28), Zhou et al (35) and Jiang et al (38).…”

“…Angiogenesis. A number of in vitro and animal studies have reported that administration of L-PRP significantly increased angiogenesis during the early phase of the tendon repair process (19)(20)(21)(22)(23)(24). It has been suggested that poor vascularity is a major factor limiting tendon healing capacity (25).…”

“…Effect on metabolism. L-PRP has been indicated to affect the metabolism of tendon cells involved in the wound healing process in in vitro and animal studies (20,23,30,35,38). In the proliferation phase, tendon fibroblasts promote the synthesis of abundant type III collagen, granulation tissue and other extracellular matrix (ECM) components (such as proteoglycans) and deposit them to the wound site.…”

“…Catabolism and anabolism are balanced in normal tendons; however, this balance is disrupted in injured tendons. Whether catabolism or anabolism prevails depends on the different types of tendon injury and healing stage (23,30). In a chronic rabbit Achilles tendinopathy model at 4 weeks after collagenase induction, Yan et al (30) observed that both P-PRP and L-PRP promoted the formation of larger collagen fibrils, but P-PRP exerted a stronger effect than L-PRP.…”

“…In fact, the current opinion is that the effect of L-PRP on metabolism is closely associated with the timing and the phase of tendon healing. Application of L-PRP at the early stage of tendon disorders or acute injury causes higher expression of collagen I, while its delivery at a later stage results in higher expression of collagen III (20,23,30,38). In other words, early delivery of L-PRP promotes matrix maturation, while late delivery impairs the matrix modeling process in tendon repair.…”