Table 3.

Clinical Outcome Studies of PRP Use in Cartilage Disease.

References	Study design	Method	PRP count	Result	Conclusion
Tucker et al. 104	Randomized controlled trial Level of evidence:1	Group A:11 patients, single PRP injection Group B:7 patients, single saline injection	PLT count 158% ± 67% of whole blood values Leukocyte quality: N/S	WOMAC scores declined for up to 3 months from baseline levels and remained low at 6 and 12 months in the PRP group. In contrast, WOMAC scores for patients receiving the saline injection were relatively unchanged for up to 12 months.	PRP modulates the local knee synovial environment by altering the inflammatory milieu, matrix degradation, and angiogenic growth factors.
Dório et al. 105	Randomized controlled trial Level of evidence:1	Group A:20 patients, PRP injection Group B:21 patients, plasma injection Group C:21 patients, saline injection All treated with 2 injections	PLT count 300% of whole blood values Leukocyte quality: poor	Change in pain from baseline at week 24 were -2.9, -2.4 and -3.5 cm for PRP, plasma and saline. There were no differences between the 3 groups at weeks 6 and 12. The PRP group showed higher frequency of adverse events, mostly mild transitory increase in pain.	PRP and plasma were not superior to placebo for pain and function improvement in knee osteoarthritis over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain.
Ngarmukos et al. 106	Prospective cohort study, with control group Level of evidence:2	Group A:51patients, 2 PRP injections Group B:43patients, 4 PRP injections injection (every 6 months)	PLT count: 430000/ L Leukocyte quality: 200/L	There were no changes of synovial inflammatory cytokines, anti-inflammatory cytokines and growth factors before 6 weeks. Both groups had significantly improved clinical outcomes from 6 weeks including VAS, patient-reported outcome measures，WOMAC and Short Form-12.	Two- or 4-PRP intra-articular injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until 1 year.
Dulic et al. 107	Prospective cohort study, with control group Level of evidence:2	Group A:111 patients, BMAC injection Group B:34 patients, PRP injection Group C:30 patients, HA injection (3 does weekly)	PLT count 600% of whole blood values Leukocyte quality: rich	The mean VAS scores showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement.	BMAC could be better in terms of clinical improvements in the treatment of knee osteoarthritis than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant.
Park et al. 108	Randomized controlled trial Level of evidence:1	Group A:55 patients, single PRP injection Group B:55 patients, single HA injection	PLT count not reported Leukocyte quality: N/S	PRP showed significantly improvement in IKDC subjective scores and the Patient Global Assessment score at 6 months. Within the PRP group, the concentrations of platelet-derived growth factors were high in patients with a score above the MCID for VAS at 6 months. The incidence of adverse events did not differ between the groups.	PRP had better clinical efficacy than HA. High concentrations of growth factors were observed in patients who scored above the MCID for clinical outcomes in the PRP group.
Bansal et al. 109	Prospective cohort study, with control group Level of evidence:2	Group A:75 patients, single PRP injection Group B:75 patients, single HA injection	PLT count：10 billion in 8 mL Leukocyte quality: poor	Significant improvements in WOMAC, IKDC scores, 6-min pain free walking distance persisted in PRP compared to HA group at 1 year. Significant decline IL-6 and TNF-α levels observed in PRP group compared to HA at 1 month.	An absolute count of 10 billion platelets is crucial in a PRP formulation to have long sustained chondroprotective effect up to 1 year in moderate knee osteoarthritis.
Raeissadat et al. 110	Randomized controlled trial Level of evidence:1	Group A:59 patients, HA injection (3 does weekly) Group B:59 patients, PRP injection (2 does weekly) Group C:60 patients, PRGF injection (2 does weekly) Group D:60 patients, Ozone injection (3 does weekly)	PLT count 400% of whole blood values Leukocyte quality: N/S	In 2 months, significant improvement was seen in all groups, but the ozone group had the best results. In 6 month, HA, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone. At the end of the 12th month, PRGF and PRP groups had better results versus HA and ozone groups in scores of VAS, WOMAC, and Lequesne index.	Patients in PRP and PRGF groups improved symptoms persisted for 12 months. Therefore, these products could be the preferable choices for long-term management.
Xu et al. 111	Prospective cohort study, with control group Level of evidence:2	Group A:34 patients, HA injection Group B:40 patients, PRP injection Group C:48 patients PRP+HA injection All treated with 3 intra-articular injection (every half a month)	PLT count not reported Leukocyte quality: poor	At 24 months, pain and function scores in the PRP+HA group were better than those in the HA and PRP alone groups. At 6 and 12 months, synovial hyperplasia in the PRP and PRP+HA groups was improved. After 6 and 12 months, the PSV, synovial EDV, S/D and RI were improved in the PRP+HA group. Complications were highest in the PRP group.	PRP combined with HA is more effective than PRP or HA alone at inhibiting synovial inflammation and can effectively improve pain and function and reduce adverse reactions. Its mechanism involves changes in the synovium and cytokine content.
Sun et al. 112	Prospective cohort study, with control group Level of evidence:2	Group A:43 patients, single HYAJOINT Plus followed by PRP Group B:42 patients, single PRP injection	PLT count 240% of whole blood values Leukocyte quality: poor	Patients receiving a single PRP experienced significantly greater improvements in VAS pain than patients receiving combined injections at 1-month follow-up. However, at 6-month follow-up, the combined-injection group achieved significantly better VAS pain reduction	Combined injections of HYAJOINT Plus and PRP achieved better VAS pain reduction than a single PRP at 6 months. The long -term benefit effect of the combination in a knee osteoarthritis need to be replicated in larger trials.
Louis et al. 113	Prospective cohort study, with control group Level of evidence:2	Group A:10 patients, MF-Saline injection Group B:10 patients, MF-PRP LD injection Group C:10 patients, MF-PRP HD injection	Group B PLT count: 1000 × 109/L Group C PLT count: 3000 × 109/L Leukocyte quality: poor	A significant decrease observed at 6 months on all scores. MF-PRP HD at 3 months and significantly higher compared to MF-PRP LD. Half of the injected PRP in the MF-PRP LD group displayed red blood cell contamination of over 8%, which was correlated with an impairment of T2max.	A single intra-articular injection of MF with or without PRP is safe and may offer significant clinical improvement for patients with osteoarthritis. High concentrations of PRP were more effective in improving articular cartilage function.
Wu et al. 114	Retrospective study, with control group Level of evidence:4	Group A:12 patients, LCG Group B:12 patients, MCG Group C:13 patients, HCG	Group A PLT count: 1000-1400 × 109/L Group B PLT count: 1400-1800 × 109/L Group C PLT count: 1800-2100 × 109/L Leukocyte quality: poor	After 2 months, compared with the HCG, articular cartilage thickness of the medial and lateral femur of the diseased side in the MCG was obviously higher. After treatment, compared with the LCG, knee joint function scores of the MCG and HCG were obviously better. Compared with the HCG, levels of MMPs and inflammatory factor in the MCG were obviously lower.	PRP combined with quadriceps training can accelerate cartilage repair and reduce inflammatory factor levels and levels of MMPs, but the treatment effect of PRP depends on platelet concentration, with the best range of 1400 1800 109/L. Too high or too low platelet concentrations will affect recovery of knee function.
Elawamy et al. 115	Randomized controlled trial Level of evidence:1	Group PRF:100 patient, pulsed radiofrequency Group PRP:100 patient, PRP injection (repeated 1 month later)	PLT count ＞300% of whole blood values Leukocyte quality: N/S	Visual analog scale was significantly lower in the PRF group compared to the PRP group at 6 and 12 months, respectively. Regarding to the postinterventional index of severity of osteoarthritis, it was significantly lower in the PRF group than the PRP group at follow-up.	Pulsed radiofrequency of the genicular nerves can be considered superior to knee intraarticular platelet-rich plasma injection for sustained pain relief and the lower severity index in patients with chronic knee osteoarthritis.
Danieli et al. 116	Prospective cohort study, with control group Level of evidence:2	Group A:31 patient, no PRP injection Group B:33 patient, PRP injection	PLT count not reported Leukocyte quality: poor	IKDC and KOOS scores showed increase at each evaluation time points after surgery in both groups, but the Group B showed a higher increase with statistically significant difference.	Those patients affected by ICRS grade III chondral injuries under-going arthroscopic chondroplasty who were also treated with PRP showed better and faster outcomes than the control group.

PRP = platelet rich plasma; PLT: Platelet count; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; VAS: visual analog scale; OA = osteoarthritis; BMAC: Bone Marrow Aspirate Concentrate; HA: Hyaluronic acid; IKDC: International Knee Documentation Committee; MCID: minimal clinically important difference; IL-6 = interleukin-6; TNF-α = tumor necrosis factor-alpha; PRGF: plasma rich in growth factors; PSV: peak systolic velocity; EDV: end diastolic velocity; S/D: systolic/diastolic ratio; RI: resistance index; MF: microfat; LD: Low Dose; HD: High Dose; LCG: low concentration group; MCG: medium concentration group; HCG: high concentration group; MMP: matrix metalloproteinases; PRF: Pulsed radiofrequency; KOOS: Knee injury and Osteoarthritis Outcome Score; ICRS: International Cartilage Repair Society.