Intra-Articular Platelet-Rich Plasma Combined With Hyaluronic Acid Injection for Knee Osteoarthritis Is Superior to Platelet-Rich Plasma or Hyaluronic Acid Alone in Inhibiting Inflammation and Improving Pain and Function

Arthroscopy. 2021 Mar;37(3):903-915. doi: 10.1016/j.arthro.2020.10.013. Epub 2020 Oct 20.


Purpose: To evaluate the effectiveness and explore the therapeutic mechanisms of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) as a treatment for knee osteoarthritis (KOA).

Methods: In total, 122 knees were randomly divided into HA (34 knees), PRP (40 knees), and PRP+HA (48 knees) groups. Platelet densities in whole blood and PRP were examined using Wright-Giemsa staining. Visual analogue scale, Lequesne, Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm scores, and postoperative complications were evaluated. High-frequency color Doppler imaging was used to observe the synovium and cartilage. Enzyme-linked immunosorbent assays were used to quantify interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinase-1 levels in synovial fluid.

Results: The platelet density in PRP was 5.13-times that in whole blood (P = .002). At 24 months, pain and function scores in the PRP+HA group were better than those in the HA-alone and PRP-alone groups (Ppain = .000; Pfunction = .000). At 6 and 12 months, synovial hyperplasia in the PRP and PRP+HA groups was improved (P < .05). After 6 and 12 months, the synovial peak systolic velocity, synovial end-diastolic velocity, systolic/diastolic ratio, and resistance index were improved in the PRP+HA group (P < .05). Complications were greatest in the PRP group (P = .008). After 6 and 12 months, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinase-1 in the PRP and PRP+HA groups decreased (P < .05), with more apparent inhibition in the PRP+HA group (P < .05).

Conclusions: 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.

Level of evidence: Level II, Prospective cohort study.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Female
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Inflammation / therapy*
  • Injections, Intra-Articular
  • Interleukin-1beta / metabolism
  • Male
  • Matrix Metalloproteinase 3 / metabolism
  • Middle Aged
  • Osteoarthritis, Knee / therapy*
  • Pain / drug therapy*
  • Pain Management / methods*
  • Pain Measurement / methods
  • Platelet-Rich Plasma*
  • Prospective Studies
  • Synovial Fluid
  • Synovial Membrane
  • Tissue Inhibitor of Metalloproteinase-1
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism


  • IL1B protein, human
  • Interleukin-1beta
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • Hyaluronic Acid
  • MMP3 protein, human
  • Matrix Metalloproteinase 3