Knee osteoarthritis is the leading joint degeneration in older adults. The disease process is characterized by articular cartilage degeneration and multiple pathologies throughout the entire joint. These lesions lead to significant joint dysfunction causing pain and severely impacting the quality of life for these patients.

Numerous treatments methods exist and are used to treat osteoarthritis of the knee. These treatments include weight loss, exercise programs, physical therapy, manipulation and a vast array of herbs, muscle topicals, vitamins and prescription medicines. Many of these interventions are effective for mild osteoarthritis and are short lived as the disease progresses. Ultimately, many of these patients undergo arthroscopic procedures which only are a segway to total knee replacement.

Intra-articular platelet rich plasma and hyaluronic acid injections have proven effective for maintaining long term relief of the symptoms of osteoarthritis and studies have shown they delay the need for total knee replacement. Neither cause intra articular infections nor significant side effects.

Hyaluronic acid is a ubiquitous carbohydrate polymer that is part of the extracellular matrix. The average adult has roughly 15 grams in the body, one third is undergoing degrading and synthesis on a daily basis. Hyaluronic acid is a major component of synovial fluid. It functions in articular cartilage by adding to the viscosity and providing cushioning and lubrication to the joint. HA provides a coating around each chondrocyte. This complex attracts and holds water and is responsible for the resistance to compression. Hyaluronic acid not only restores synovial fluid viscosity, viscoelasticity and mechanical properties but stimulates endogenous HA production from the chondrocytes as well as the synoviocytes. HA is abundant in extracellular matrices throughout the body and contributes to tissue hydrodynamics, movement and the proliferation of cells and participates in several cell surface receptor interactions. These actions contribute to tissue regeneration, inflammation and angiogenesis which are phases of wound repair. There is also some limited evidence that hyaluronic acid may help with pain control.

In the osteoarthritic knee joint, it is estimated that at least 50% of the synovial fluid has decreased making supplementation with hyaluronic acid needed for cushioning, lubrication and pain control.

Platelet Rich Plasma is an autologous blood concentrate that is rich in cytokines, growth factors and bioactive proteins. It has been used in all fields of medicine, dentistry and veterinary due to the regenerative capabilities of this concentrate. Platelets, as the main component of the PRP, contain more than 1100 different proteins with post-translational modifications, resulting in over 1500 bioactive factors. These factors include immune messengers, growth factors, enzymes and their inhibitors and other factors which participate in tissue repair and wound healing. Since this is an autologous product, concerns for contamination or allergic reaction are dispelled.

In the knee, much of the cartilage in the joint area has little blood supply and therefore healing of damaged tissue is slow and there is slow cell turnover. The use of PRP in these areas speeds up the healing process by accelerating neovascularization. This process increases blood supply and precipitates an influx of nutrients needed for the proliferation and differentiation of the cells.

Various proteins and other substances necessary for tissue repair and healing are secreted from the granules located on the platelets. There are three types of granules (alpha, delta and lambda) inside the platelets with alpha being the most abundant. On each platelet there are approximately 50-80 granules. Alpha granules release more than 300 soluble proteins. These proteins are involved in clotting, inflammation, cell growth, cell adhesion and host defense.

Delta granules contain molecules which stimulate clotting. These include calcium, magnesium, adenosine and bioactive amines such as serotonin and histamine.

Lambda granule is the third type of granule and belongs to the lysosomal type of cell. These contain enzymes necessary in protein, lipid and carbohydrate degradation. They are involved in removing the debris from damaged tissue and removing infectious agents.

From alpha granules alone, the following are released after activation;

  • Adhesive proteins
  • Growth Factors
  • Angiogenic Factors
  • Chemokines
  • Clotting factors and their inhibitors
  • Membrane proteins
  • Immune Mediators

Six Growth Factors and Their Biologic Function

  1. Platelet Derived Growth Factor (PDGF)- Enhances collagen synthesis, proliferation of bone cells, fibroblast chemotaxis and proliferative activity, macrophage activation.
  2. Transforming Growth Factor B (TGF-B)- Enhances synthesis of type 1 collagen, promotes angiogenesis, stimulates chemotaxis of immune cells, inhibits osteoclast formation and bone resorption
  3. Vascular Endothelial Growth Factor (VEGF)- Stimulates angiogenesis, migration and mitosis of endothelial cells, increases permeability of the vessels, stimulates chemotaxis of macrophages and neutrophils
  4. Epidermal Growth Factor (EGF)- Stimulates cellular proliferation, differentiation of epithelial cells, promotes cytokine secretion by mesenchymal and epithelial cells
  5. Insulin like growth Factor (IGF)- Promotes cell growth, differentiation, recruitment in bone, blood vessel, skin and other tissues and stimulates collagen synthesis together with PDGF
  6. Fibroblast Growth Factor (FGF)- Promotes proliferation of mesenchymal cells, chondrocytes and osteoblasts, stimulates the growth and differentiation of chondrocytes and osteoblasts

PRP is rich in bioactive molecules. Along with leukocytes, this combination enhances the healing process by removing the potential microbes, modulating the removal of damaged tissues and stimulating the overall repair.


J of Ortho Surg Jan 2, 2020

In this meta-analysis, Knee Osteoarthritis Outcome Scores (KOOS) did not differ significantly. However, other scores such as the International Knee Documentation Committee (IKDC) differed significantly, favoring platelet rich plasma, especially in the long term.

The authors stated that PRP and HA have the potential to decrease hyperplasia of the synovial membrane and alter cytokine levels, changing the homeostasis of the joint. This can result in clinical improvements in the arthritic knee joint.

Inconsistent results in the studies may be the result in the number of injections in the PRP and HA groups.

Conclusion- Our hypothesis appears not to be confirmed because the PRP and HA groups did not differ significantly with respect to the KOOS score. However, significant difference can be seen in other scores. Based on this current evidence, PRP appears to be better for pain and functional self-reported improvement.

Am J Sports Med 2015 Jul;43(7):1575-82 PMID 25952818

Purpose: To evaluate the benefit provided by platelet rich plasma injections to treat knee joint degeneration in comparison to hyaluronic acid.

Conclusion: PRP does not provide superior clinical improvement with respect to HA.

Author’s note: Although the above are older studies, both hyaluronic acid and platelet rich plasma have a place in the treatment of knee osteoarthritis. The mechanism of action of HA and PRP are different but are synergistic in their actions to change the microenvironment of the arthritic knee joint. They mediate and stimulate repair and regeneration and can be used sequentially in the treatment of knee osteoarthritis. Either or is not the answer, both is the ultimate solution to modify the disease process and maintain the microenvironment of the joint.

Integrative Practice Solutions has been collaborating and instructing medical practitioners in the treatment of the arthritic knee for over a decade. The Advanced Arthritis Relief Protocol is a patented program of hyaluronic acid injections done with fluoroscopy, unloading knee bracing and physical therapy. The outcomes far surpass the national average for hyaluronic acid alone. This program has given relief to thousands of osteoarthritic patients and delayed the need for invasive surgeries.

Juventix Regenerative Medical, the sister company to IPS, is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA cleared and designed for safety, sterility and effectiveness. Our kits are scientifically manufactured to provide a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes that are critical to the regenerative process.

Integrative Practice Solutions and Juventix Regenerative Medical together provide the ultimate treatment for osteoarthritis of the knee.


Regenerative Regards,


Dr. Robert McGrath

Leave a Reply