As a carrier of multiple growth factors, PRP is widely used in the treatment of cartilage lesions in the early stages [15, 25, 33]. To date, the results of previous research and our study have shown a positive clinical efficacy of PRP in inhibiting inflammatory reactions, alleviating pain, and promoting the repair of cartilage lesions [21, 34]. However, because of the difference in the preparation technology of PRP, PRP with diverse components, especially the concentration of leukocytes, may lead to adverse effects in the treatment of cartilage lesions. [21]
In this study, the short-term results demonstrated a significant difference between the clinical efficacy of P-PRP and L-PRP in treating knee cartilage lesions. The VAS and WOMAC scores in the two groups remained stable from the end of the therapy to the 6-month follow-up, but they became significantly worse at the 1-year follow-up. According to previous studies, such a low score at the end of the therapy was often explained by the low patient activity level, rather than from any persistent knee pain or functional limitation [35]. On the other hand, no statistically significant difference was found in WOMAC total, while the WOMAC pain score in the P-PRP group was significantly better than that in the L-PRP group 6 weeks after treatment. With respect to adverse events, the P-PRP group showed better safety and fewer complications, which coincided with those reported in other studies [36].
Once injured, the cartilage has a very limited intrinsic healing capacity. With fewer vessels, nerves, and lymphoid tissue around, cartilage lesions undergo repair only with limited growth factors and stem cells [37]. On the other hand, a rather part of cartilage lesions is attributed to knee degeneration, which is a multifactorial and irreversible disease. PRP, with various high concentrations of growth factors, including transforming growth factor β, platelet-derived growth factor, insulin-like growth factor, basic fibroblast growth factor, vascular endothelial growth factor, and epidermal growth factor, can promote the proliferation of chondrocytes and the secretion of cartilage matrix, thus inducing the regeneration of cartilage. Moreover, the anti-inflammatory ingredients in PRP help to protect chondrocytes. [16, 20, 25, 29, 31, 38, 39]
Despite the benefit of PRP in treating cartilage lesions owing to the abundant growth factors, the clinical efficacy of PRP remains a controversial issue, mostly attributed to the different concentrations of leukocytes in PRP. In recent years, several subsequent studies have reported that despite its positive anti-infection effects, L-PRP may lead to the inhibition of the repair of cartilage lesions due to its high concentration of leukocytes. Similar to the results of previous studies, our study recorded more adverse events in the L-PRP group, with mild swelling and local pain. Among them, the fever of one febrile patient in the L-PRP group lasted for 1 week until further arthroscopic debridement was performed.
Inflammatory factors, mainly interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α), play a key role in the development of osteoarthritis (OA). Sundman et al. [39] first reported the influence of cellular composition on the growth factor and catabolic cytokine concentrations of PRP. In their study, it was found that platelets increased anabolic signaling and in contrast, leukocytes increased catabolic signaling molecules. Cavallo et al. [26] demonstrated distinct effects on human articular chondrocytes induced by L-PRP and P-PRP in vitro. They found that P-PRP stimulated chondrocyte anabolism by the expression of type-II collagen and aggrecan, whereas L-PRP promoted catabolic pathways involving various cytokines. The findings of Rios et al. [38] suggested that anabolic and anti-inflammatory joint responses depend on the leukocyte and platelet concentrations of PRP preparation. Moreover, P-PRP is recommended to be more effective for the medical treatment of patients with OA and inflammatory synovitis. Despite several RCTs on this topic, L-PRP and P-PRP were directly compared in only a single trial, while they were each compared with common references (hyaluronic acid or placebo) in multiple trials [33].
Considering the controversial clinical efficacy of PRP with different concentrations of leukocytes, we decided to conduct an RCT with a larger sample size, a longer follow-up period, and higher evidence. Different extracting approaches to acquire P-PRP and L-PRP were also applied in the study. Presently, as various preparation systems have been used to acquire PRP, there can be a huge difference in the concentration of growth factors and leukocytes in PPR. Bausset et al. [40] evaluated the effect of different centrifugation speeds and time storage durations on platelet quantity and quality. Approximately 130 and 250 g successive speed centrifugations were recommended to obtain a highly concentrated and pure PRP product. However, a previous study showed unsatisfactory retrieval rates of platelets by such a method [36]. In our study, two centrifugations (the first at 1,800 rpm for 15 min to separate erythrocytes and a second at 3,500 rpm for 10 min to concentrate platelets and separate leukocytes) were applied to produce PRP. For convenience, we chose to make the same volume for the two types of PRP. Considering the difference in extracting methods between P-PRP and L-PRP, the concentration of platelets and leukocytes in L-PRP was higher than that in P-PRP, which may also be the reason for a higher number of early-stage adverse events in the L-PRP group and similar long-term clinical efficacy between the two groups. As there are more adverse events (including a case with persistent fever) with L-PRP, P-PRP is recommended for safety.
Although our study showed better early clinical efficacy and safety of P-PRP in treating knee cartilage lesions compared with those of L-PRP, no significant difference was observed in the long-term follow-up. More RCTs with larger sample sizes and longer follow-up periods are needed. There are also several obstacles to overcome, such as improving methods to extract and purify the product and the selective activation of various components of PRP.
Our study had some limitations. First, the PRP injection was limited and not equal among patients. Second, the sample size was small, and the follow-up period was short. Restricted to the will of patients, no further blank controls were conducted. Finally, we were unable to perform either a routine second-look arthroscopy or an MRI. In addition, we lost nearly 8% of our patients when they refused to participate in follow-up visits.