Knee osteoarthritis is one of the most common joint conditions, often causing pain, stiffness, swelling, and reduced mobility. It occurs when cartilage within the knee gradually wears down, leading to inflammation and changes in the structure and function of the joint. For many people, knee osteoarthritis can make daily activities such as walking, climbing stairs, exercising, or standing for long periods more difficult.
While advanced cases may eventually require surgical treatment, many patients with early- to mid-stage knee osteoarthritis seek nonsurgical options that can help reduce pain and support joint function. One treatment that has gained attention in regenerative medicine and orthopedics is platelet-rich plasma, commonly known as PRP.
In this study published in Frontiers in Medicine, researchers compared the clinical effectiveness of a single intra-articular PRP injection with sequential PRP injections in patients with early- to mid-stage knee osteoarthritis. The goal was to better understand whether multiple PRP injections may provide longer-lasting benefits compared with one injection alone.
What Is Platelet-Rich Plasma?
Platelet-rich plasma is prepared from a patient’s own blood. A blood sample is collected and processed through centrifugation, which separates the blood into different components. The platelet-rich portion is then collected and used for injection.
Platelets are best known for their role in blood clotting, but they also contain growth factors, cytokines, and other biologically active molecules involved in healing and tissue repair. In regenerative medicine, PRP is studied for its ability to support the body’s natural repair processes, regulate inflammation, and improve the local joint environment.
For knee osteoarthritis, PRP is typically injected directly into the joint space. This allows the concentrated platelets and growth factors to reach the affected tissues more directly, where they may help reduce inflammatory activity and support cartilage-related repair pathways.
Study Overview
This study included 94 patients diagnosed with early- to mid-stage knee osteoarthritis between 2022 and 2024. Patients were divided into two groups: 55 received a single intra-articular PRP injection, while 39 received sequential PRP injections.
The single-injection group received one PRP injection at the beginning of treatment. The sequential-injection group received three PRP injections total, administered every two weeks at week 0, week 2, and week 4.
All PRP injections were performed under ultrasound guidance, which helps improve accuracy by allowing the clinician to visualize the joint space during the procedure. Each patient received 3 mL of PRP into the affected knee joint.
Researchers followed patients for six months and compared several outcomes, including:
- Inflammatory markers in the blood
- Cartilage-related markers in the synovial fluid
- Knee pain scores
- Osteoarthritis severity scores
- Knee function scores
- Complications or adverse reactions
This gave researchers a broader view of how PRP affected both symptoms and biological markers associated with knee osteoarthritis.
Key Findings From the Study
Both single and sequential PRP injections produced meaningful improvements in patients with early- to mid-stage knee osteoarthritis. At follow-up, both groups showed significant improvements in pain, knee function, and osteoarthritis-related assessment scores.
The researchers measured pain using the visual analog scale, or VAS. They also used the WOMAC score to evaluate osteoarthritis-related symptoms and the Lysholm score to assess knee function. In both groups, patients showed improvements at 1, 3, and 6 months after treatment.
However, the sequential PRP group showed stronger results at the six-month follow-up. Compared with the single PRP group, patients who received sequential injections had lower pain scores, better WOMAC scores, and higher Lysholm knee function scores at six months.
This suggests that while one PRP injection may be beneficial, sequential PRP injections may provide more sustained improvement in pain relief and joint function over time.
Effects on Inflammation and Joint Biomarkers
One of the most important parts of this study was its focus on inflammatory and cartilage-related markers. Knee osteoarthritis is not only a condition of cartilage wear; it also involves inflammation and biochemical changes within the joint.
Researchers measured several inflammatory markers, including interleukin-1β, interleukin-6, and tumor necrosis factor-alpha. These inflammatory molecules are commonly associated with joint inflammation and cartilage breakdown.
At six months after treatment, both groups showed reduced levels of these inflammatory markers compared with pretreatment levels. However, the sequential PRP group showed greater reductions than the single PRP group.
The study also measured synovial fluid markers, including matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Matrix metalloproteinase-3, or MMP-3, is involved in cartilage matrix breakdown, while TIMP-1 helps inhibit enzymes that contribute to cartilage degradation.
After treatment, both groups showed decreased MMP-3 and increased TIMP-1. The sequential PRP group again showed more favorable results at six months, with lower MMP-3 and higher TIMP-1 compared with the single PRP group.
These findings suggest that PRP may support knee osteoarthritis improvement not only by reducing pain, but also by influencing inflammatory activity and cartilage-related biochemical markers within the joint.
Why Sequential PRP May Offer Longer-Lasting Benefits
The study found that both treatment approaches were helpful, but sequential PRP injections appeared to provide stronger medium-term benefits by the six-month mark. One possible explanation is that repeated PRP exposure may provide more sustained biological signaling within the joint.
Because PRP contains growth factors and signaling molecules, multiple injections may help maintain a more supportive joint environment over time. This may allow for continued regulation of inflammation, improved tissue response, and longer-lasting symptom relief.
The authors noted that single PRP injections can still offer meaningful improvement, especially for patients with early-stage knee osteoarthritis or milder symptoms. However, sequential PRP may be more beneficial for patients with moderate knee osteoarthritis, persistent pain, or greater functional limitation.
Safety and Tolerability
The study also evaluated complications in both groups. A small number of patients experienced temporary reactions such as knee redness, knee pain, or transient fever. There was no significant difference in complication rates between the single and sequential PRP groups, and all reported cases improved after treatment.
These findings suggest that both single and sequential intra-articular PRP injections were generally well tolerated in this patient group. The authors emphasized the importance of careful injection techniques, sterile procedure, and ultrasound guidance to support safety and accuracy.
Why This Research Matters
This study is valuable because it compares two practical PRP approaches for knee osteoarthritis: one injection versus a series of injections. For patients and clinicians, the question is not only whether PRP may help, but also how treatment timing and frequency may influence results.
The findings suggest that PRP can be a useful nonsurgical option for early- to mid-stage knee osteoarthritis, with benefits related to pain relief, function, inflammation, and joint-related biomarkers. While both approaches showed clinical improvement, sequential PRP injections demonstrated stronger six-month outcomes, suggesting a possible advantage for longer-term symptom control and joint function.
As regenerative medicine continues to develop, studies like this help refine how PRP may be used more effectively. Understanding treatment frequency, patient selection, and biological response is an important step toward improving outcomes for individuals with knee osteoarthritis.
A Promising Nonsurgical Option for Knee Osteoarthritis
Platelet-rich plasma continues to be an important area of research in orthopedic and regenerative medicine. Its ability to deliver concentrated growth factors and biologically active molecules directly into the joint makes it a promising option for patients with early- to mid-stage knee osteoarthritis.
This study found that both single and sequential PRP injections improved pain, function, and inflammatory markers. However, sequential PRP injections appeared to offer more sustained benefits at six months, especially in relieving pain and improving knee joint function.
While additional studies can help further clarify ideal treatment protocols, this research supports the growing role of PRP as a regenerative medicine approach for joint health, mobility, and nonsurgical knee osteoarthritis care.
Source Zhao W, Chen L, Wang D, Wei X. Comparison of clinical efficacy of sequential and single intra-articular injection of platelet-rich plasma in treatment of early/mid-stage knee osteoarthritis. Front Med. 2025 Dec 11;12:1707979. doi: 10.3389/fmed.2025.1707979. Available from: https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1707979/full
Related Treatment Pages