what is prolotherapy
with platelet rich plasma?

Platelet Rich Plasma Therapy repairs degenerative joints using your own healing growth factors

In this article, we discuss new research on the clinical benefits of Platelet Rich Plasma Therapy (PRP). Sometimes PRP is referred to as PRP Therapy, PRP injection therapy, plasma replacement therapy, or simply PRP shots.

  • PRP treatment takes your blood, like going for a blood test, and re-introduces the concentrated blood platelets from your blood into areas of chronic joint and spine deterioration.
  • Your blood platelets contain growth and healing factors. When concentrated through simple centrifuging, your blood plasma becomes "rich" in healing factors, thus the name Platelet RICH plasma. Platelets play a central role in blood clotting and wound/injury healing.
  • The procedure and preparation of therapeutic doses of growth factors consist of an autologous blood collection (blood from the patient), plasma separation (blood is centrifuged), and application of the plasma rich in growth factors (injecting the plasma into the area.) In our office, patients are generally seen every 4-6 weeks. Typically three to six visits are necessary per area.

A closer look at PRP, how it works and the research behind it

As mentioned, Platelet rich plasma (PRP) is the injection of concentrated platelets (5-6x the concentration in the blood), which release growth factors to stimulate recovery in non-healing soft tissue injuries.

  • After an acute injury, platelets converge on the area of injury to first stop the bleeding  area to help stop the bleeding. Once they reach the injury, they change shape to best cover the wound. When they change shape, they release their contents, which include many of the most powerful stimulators of healing, such as platelet-derived, transforming, fibroblastic, and vascular endothelial growth factors. These are explained below.
  • These growth factors are crucial for the proliferative phase of healing that involves the manufacturing of collagen, fibrocartilage and hyaline cartilage. During the primary inflammatory phase of healing, the functions of activated platelets involves adhesion, aggregation, clot retraction, pro-coagulation, cytokine signaling, chemokine release, growth factor release and anti-microbial effects.
  • PRP causes proliferation of fibroblasts and other immune cells, thereby accelerating the regeneration of injured tissues.
  • Activated platelets also secrete stromal cell derived factor 1 alpha which supports primary adhesion and migration of mesenchymal stem/stromal cells.
  • PRP helps recruit undifferentiated (stem cells) cells to the site of injury, as well as enhance mesenchymal stem/stromal cells differentiation and proliferation.

It is evident from the above, that PRP has many potential uses in the treatment of the pain and disability of osteoarthritis. PRP has been shown to enhance tendons, ligaments, meniscus, and the extracellular matrix of both intervertebral discs and articular cartilage. Even subchondral bone lesions can be improved with intraosseous injections of PRP.

PRP has an enormous amount of potential to reverse the physiology of osteoarthritis. One of the primary ways it does so is by changing the environment of the diseased knee joint to stimulate healing by increasing the volume of the natural knee lubricants and thereby improving and protecting the cartilage. PRP also enhances the synthesis of synovial fluid from synovium- and cartilage-derived cells.

The friction coefficient of cartilage with PRP is about the same as that of normal synovial fluid. Specifically, PRP improves the “nutritional soup” of the synovial fluid by decreasing the friction coefficient which minimizes forces on the articular cartilage. This, along with its ability to stimulate cell migration, proliferation, differentiation of progenitor/stem cells, and joint homeostasis make it an excellent treatment modality to reverse the destructive physiology of osteoarthritis.

Although the application of Platelet Rich Plasma has been around for decades, the treatment has become a more recent option for doctors and patients.

In 2012, researchers at the University of Rochester wrote (1) in the medical journal Arthritis Research and Therapy:

“Chronic complex musculoskeletal injuries that are slow to heal pose challenges to physicians and researchers alike. Orthobiologics is a relatively newer science that involves application of naturally found materials from biological sources (blood platelets), and offers exciting new possibilities to promote and accelerate bone and soft tissue healing. Platelet-rich plasma (PRP) is an orthobiologic that has recently gained popularity as an adjuvant treatment for musculoskeletal injuries. . .  The relative ease of preparation, applicability in the clinical setting, favorable safety profile, and possible beneficial outcome make PRP a promising therapeutic approach for future regenerative treatments.”

In the years since then, there have been hundreds of research papers published in medical journals around the world that describes the benefits and sometimes shortcomings of PRP treatments. We are going to present some of that research here.

As PRP gains popularity and more research validates its usefulness and reliability to patients, it is important to remember that PRP is just one proliferant available for regenerative injection therapy. At Caring Medical we use numerous regenerative treatments depending on the severity of the pain or injury. This includes dextrose Prolotherapy, PRP, and stem cell therapy which can provide effective and safe treatments, leading to permanent healing of chronic pain and sports injury and avoidance of elective surgery.

Growth and healing factors in PRP, what make PRP work

Above we described the many actions of the blood platelets in injury repair. Let's look at the research.

Doctors at the University of Florence published findings (2) in which they described the growth, healing, and repair factors found in platelet rich plasma. These are the healing factors and what they do:

  • PDGF (Platelet-derived Growth Factor) initiates connective tissue healing through the promotion of collagen and protein synthesis.
    • The primary effect of PDGF seems to be its mitogenic activity to mesoderm-derived cells such as fibroblasts (produces collagen a building block of new cartilage),
    • vascular muscle cells (new blood vessels to bring healing factors to the injury),
    • glial cells (protects nerves) and chondrocytes (the stuff cartilage is made of - see our article on Extracellular Matrix).
    • The most important specific activity of PDGF is the creation of cartilage.
  • VEGF (Vascular Endothelial Growth Factor) is the major regulator of vasculogenesis and angiogenesis and playing an important role in tissue regeneration. It does so by creating new highways of blood vessels for the healing factors to get to the site of the injury.
  • Transforming Growth Factor (TGF) including TGF-b1 stimulates chondrocyte (Cartilage growth) and decreases the catabolic activity (breakdown of cartilage). There is also research to suggests that TGF-bi stimulates stem cell activity in the injured area.

The summary of a recent research article adequately sums up the suggested use these healing factors in Platelet Rich Plasma Therapy in repairing and regenerating cartilage. The University of Torino and the University of Milan doctors writing in the medical journal Biomed Research International say:

"The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidence in the literature has shown that PRP may be helpful both as an adjuvant for the surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis."(3)

Is PRP an anti-inflammatory? Do we want PRP to be an anti-inflammatory?

The above effects of Platelet Rich Plasma Therapy on rebuilding cartilage and soft tissue are in effect PRP awakening the inflammatory response to healing. This also causes a degree of confusion even among medical professionals. In essence, they say "Do we want PRP to be an anti-inflammatory?"

This is the basis of Orthokine, a PRP "product" that reduces inflammation and tried by world-famous athletes. The treatment has limited appeal because it is only an anti-inflammatory and does not promote healing.

In recent research, doctors writing in the American Journal of Sports Medicine tested different types of PRP formulas and they found that they may reduce inflammation when inflammation was induced by Interleukin-1, the peptide responsible for cell signaling and opening the healing pathways.(4) 

In this case, PRP formulas manipulated to act as anti-inflammatories are not helpful for long-term healing.

This is why you get conflicting evidence surrounding Platelet Rich Plasma Therapy

A patient will often explore non-surgical methods of joint repair after they have been to a doctor that is recommending surgery. When they return to that doctor with questions about PRP they may hear that PRP is unproven, doesn't work, no research to support it.

This entire article shows you the research that is supportive. I will also show you research that is not-supportive and why.

PRP may not work if the doctor does not use standardized procedures

PRP treatments are easy to learn. They are after all injections. If your doctor is experienced in giving cortisone injections, they will be experienced in giving PRP injections. But is this true?

Cortisone is a single injection, PRP's best chance to work to its maximum benefit is when it is offered as part of a comprehensive program of joint healing. That means more than one injection. At Caring Medical, we off PRP treatment as part of a comprehensive Prolotherapy program that treats all of the knee: ligaments, tendons, cartilage, and the entire diseased and dying knee joint.

  • The lack of standardization is discussed in the medical journal Odontology by researcher Tomoyuki Kawase of Niigata University in Japan.(5)

    • Platelet Rich Plasma Therapy is very promising BUT calls for standardization for doctors who want to use Platelet Rich Plasma Therapy (PRP) in the treatment of chronic joint pain.
    • This research and similar papers indirectly and clearly suggest that Platelet Rich Plasma Therapy results will vary depending on the level of experience and training the doctor has in utilizing PRP.

Dr. Kawase says this is clearly alluded to in the research:

  • Platelet-rich plasma has been widely investigated and applied to regenerative medicine.
    • PRP use is supported by evidence that PRP contains high concentrations of platelet-related growth factors and normal concentrations of plasma-derived fibrinogen, both of which contribute to the regenerative process.
    • Additionally, its superior cost-efficacy versus conventional therapies is attractive to many clinicians.
    • However, the current disadvantages of PRP include a relatively complicated preparation procedure and doctor's effectiveness in giving PRP  treatment.

The high degree in variability in treatment procedures among practitioners who use Platelet Rich Plasma

Doctors in Italy at the Rizzoli Orthopedic Institute and the University of Bologna expressed concern over the lack of standardization among doctors using Platelet Rich Plasma Therapy in their study. (6) The researchers do acknowledge that the role of PRP in bone, tendon, cartilage, and ligament tissue regeneration has been shown in numerous preclinical studies published within the last 10 years to have delivered very promising results but many key questions remain unanswered and controversial results have arisen.

Writing in the medical journal Biomed Research International they also call for  studies to define the dosing, timing, and frequency of PRP injections, different techniques for delivery and location of delivery, optimal physiologic conditions for injections, and the concomitant use of recombinant proteins, cytokines, additional growth factors, biological scaffolds, and combined use of PRP and stems cells to develop optimal treatment protocols that can effectively treat various musculoskeletal conditions.

Back to treating the whole knee with a comprehensive program:

See what these researchers are suggesting, optimal physiologic conditions for injections, and concomitant use of other growth factors, this is what we do at Caring Medical. Optimal physiologic conditions meaning that the patient:

In 2017, doctors writing in the medical journal Pain Physician wrote:

"It is incumbent upon anyone using a specific PRP product to understand its precise formulation and consistency as well as the rationale for the technique used in its production and application. The lack of standardization and quality
control in addition to the diverse applications of PRP and outcomes, make it difficult to generate convincing data."(8)

The number of platelets. Is this important?

PRP therapies for osteoarthritis have been developed based on several assumptions beyond tissue homeostasis (the repair of tissue while a joint continues to function): (1) anti-inflammatory effects of chemokines, and subsequent anti-catabolic effects; (2) immune modulation and (3) anabolic actions of growth factors. However, the number of platelets, for unit of volume, is not necessarily associated with clinical success in the conditions in which PRP are used. Platelets contain proteins with opposing actions; hence, increasing platelet number does not modify this balance.

What the researchers are calling for are protocols that are used at Caring Medical every day and based on over 28 years of clinical experience in Prolotherapy and regenerative injection therapy and well documented in our own studies.

Unfortunately, like many new and upcoming treatment modalities, there are good and not-so-good uses of the technique. Some physicians are rapidly jumping on the PRP bandwagon without having much injection experience or without any knowledge except for a weekend course in the use of PRP. Prolotherapy is a specialized medical technique. It not only involves being able to choose the right proliferant for the patient's particular pain complaint, but it also involves making a proper diagnosis, and then fully treating the injury. This is what we call Comprehensive PRP Prolotherapy.

PRP research: PRP helps bone growth

Researchers at the University of Connecticut set out to discover how different Platelet Rich Plasma Therapy (PRP) methods affected human muscle, cell, and bone tissue.(9) They sought to recommend a standardized platelet concentration (the optimal amount of blood platelets reintroduced into the arthritic joint).

They found that PRP helps bone, muscle, and tendon cells proliferate no matter the cell concentration level. This proliferation leads to the healing of damaged tissue and curing of chronic pain and injury.

PRP as an alternative to osteochondral lesion surgery

Recently, the American Journal of Sports Medicine published an article on the use of PRP for osteochondral lesions.(10) The results were great and the researchers concluded that “in our hands, PRGF [platelet-rich growth factors, a form of PRP] has now become the first line of nonoperative treatment in these lesions.”

  • This study looked specifically at osteochondral lesions of the talus bone of the ankle. 29 patients age 18-60 participated in the study and they received either Hyaluronic Acid injections or PRP injections. While both Hyaluronic Acid and PRP decreased pain scores and increased function, PRP had significantly higher scores. Given that the traditional treatments of immobilization, bracing, and NSAIDs are often unsuccessful, the researchers were encouraged by these results, especially given that surgery is the only other option once conservative treatments fail.

In a study from Italy's National Cancer Institute Stem Cell Transplantation Unit, doctors found that following extraction of benign giant cell tumors that resulted in large defects, a PRP gel accelerated healing and growth of bone and achieved good functional results without promoting local cancer recurrence.(11)

For more research please see our article: Can osteoarthritis bone damage be repaired with Platelet Rich Plasma?

PRP Therapy for knee problems

There is a reason researchers are trying to find ways to regenerate cartilage. The reason is regenerative medicine is the future and the days of removing tissue are clearly limited. The doctors at the University of Rochester mentioned at the top of this article, found that two PRP treatments with 4-week intervals, improved the pain, stiffness, and functional capacity of patients with knee osteoarthritis. Additionally, Improvements in quality-of-life were meaningful after injections.(12)

Researchers at the University of Washington are the latest to join in on the discussion on the effectiveness of Platelet Rich Plasma Therapy for sports injuries. In their Platelet rich plasma therapy research review they noted that "Interest in platelet-rich plasma (PRP) has skyrocketed over the last decade. . . interest from the public has fueled increased utilization of PRP for musculoskeletal conditions, particularly those that are difficult to treat such as chronic, degenerative tendinopathy and osteoarthritis."(13)

PRP treatment treat the whole joint and may prevent future degeneration

From the Department of Orthopedic Surgery, Center for Tissue Regeneration and Repair, University of California, Davis: "PRP has the therapeutic potential not only to promote tissue regeneration, but also to contribute to articular cartilage lubrication by decreasing the friction coefficient and minimizing wear."(14)

PRP treatment may improve stability in post-operated on knees

Doctors at the OASI Bioresearch Foundation in Italy published in the journal Sports Health, these findings:

"Patients with previous cartilage shaving and microfracture showed significant improvement at 6 and 12 months following post-surgical PRP injections. Therefore, PRP injections could be considered as an adjuvant in postoperative treatment of these patients."(15)

Platelet Rich Plasma for hip osteoarthritis

Our website is filled with articles on PRP for hip osteoarthritis:

Please see:

In the study cited above from doctors at the University of Florence, researchers found that a majority of patients receiving PRP for hip osteoarthritis had significant pain reduction at 6-7 weeks, which was sustained at 6 months, with a better range of motion.(16)

Researchers from the Rizzoli Orthopedic Institute in Italy published their findings in the American Journal of Sports Medicine which showed intra-articular PRP injections offered a significant clinical improvement in patients with hip osteoarthritis without relevant side effects.(17)  Interestingly when the same doctors added hyaluronic acid to the PRP treatment, no difference in successful outcome was found. The PRP worked just as good by itself.

Even after hip surgery, PRP was effective in reducing pain that continued after surgery.(18)

PRP Therapy for back pain

In the medical journal Pain Physician, doctors in China wrote of "A New Technique for the Treatment of Lumbar Facet Joint Syndrome Using Intra-articular Injection with Autologous Platelet Rich Plasma."

In this research, they looked at 19 patients with lumbar facet joint syndrome (8 men, 11 women between the ages of 38 and 62) who received lumbar facet joint injections with autologous PRP under x-ray fluoroscopic guidance.

Patients were followed up immediately, at one week, one month, 2 months, and 3 months following treatment, and progress was measured with a series of standardized scoring systems.

  • At one week after treatment, low back pain reduced significantly
    • The outcomes were assessed as "good" or "excellent" for 9 patients (47.37%) immediately after treatment,
    • 14 patients (73.68%) at one week,
    • 15 patients (78.95%) at one month,
    • 15 patients (78.95%) at 2 months,
    • and 15 patients (78.95%) at 3 months.

In the short-term period of 3 months, the new technique of lumbar facet joint injection with autologous PRP is effective and safe for patients with lumbar facet joint syndrome.19

PRP and Shoulder Problems

Please see these updated articles on the use of Platelet Rich Plasma and stem cell therapy for Rotator Cuff and other shoulder problems. Another problem that can be addressed with PRP is frozen shoulder, medically referred to as adhesive capsulitis. In this article, we discuss PRP alternatives to surgery for glenoid labral tears.

Will Platelet rich plasma therapy work for me?

This question is subject of course to many factors, the least of which is getting Comprehensive Prolotherapy that includes Platelet Rich Plasma versus getting a single, or two-treatment program.  The good news is that even in research where two PRP treatments are given, without supportive Prolotherapy, results were very positive. Even in patients who had continued Knee Pain after knee surgery.  “PRP treatment showed positive effects in patients with knee osteoarthritis. Operated and non-operated patients showed significant improvement by means of diminishing pain and improved symptoms and quality of life.”14

Our paper on the Platelet Rich Plasma PRP Injection Technique printed in the Journal of Prolotherapy provides the basic information on PRP's use as an effective proliferant for Prolotherapy treatments.

An experienced Prolotherapist can use PRP Prolotherapy in a safe and effective way to heal common joint injuries. One common issue occurring in the PRP field is that a number of practitioners are performing solely PRP, and not using dextrose  Prolotherapy to address the underlying joint instability that most likely led to the injury in the first place.  Comprehensive Prolotherapy involves not only providing growth factors for healing and/or cartilage regrowth, but addressing the underlying cause of the problem. Our study on the use of PRP Prolotherapy for the treatment of meniscus tears published in Practical Pain Management discusses the comprehensive approach and shows how its use leads to avoidance of surgery in an otherwise surgically-treated medical problem: meniscus tears.

As with any medical procedure, its success is determined by the experience, compassion, and technique of the practitioner providing the treatment. Platelet rich plasma used for injection is no different.

PRP has been shown effective for labral tears of the hip and shoulder labrum tears, as well as degenerated meniscus and meniscus tears. The scientific literature is full of reports of soft tissue injuries treated with PRP including tendinopathy, tendinosis, acute and chronic muscle strain, muscle fibrosis, ligament sprains, and joint capsular laxity, in addition to various degenerative disorders in your joints. Especially exciting is PRP's use for regenerating cartilage. Most recently research has shown PRP to be an effective treatment for knee osteoarthritis.


1. Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy – future or trend? Arthritis Res Ther. 2012 Aug 8;14(4):219. [Google Scholar]
2 Civinini R, Nistri L, Martini C, Redl B, Ristori G, Innocenti M. Growth factors in the treatment of early osteoarthritis. Clinical Cases in Mineral and Bone Metabolism. 2013;10(1):26-29. doi:10.11138/ccmbm/2013.10.1.026. [Google Scholar]
3. Marmotti A, Rossi R, Castoldi F, Roveda E, Michielon G, Peretti GM. PRP and articular cartilage: a clinical update. BioMed research international. 2015 May 5;2015.[Google Scholar]
4. Osterman C, McCarthy MB, Cote MP, Beitzel K, Bradley J, Polkowski G, Mazzocca AD. Platelet-Rich Plasma Increases Anti-inflammatory Markers in a Human Coculture Model for Osteoarthritis. Am J Sports Med. 2015 Jun;43(6):1474-84. [Google Scholar]
5. Kawase T. Platelet-rich plasma and its derivatives as promising bioactive materials for regenerative medicine: basic principles and concepts underlying recent advances. Odontology. 2015 Jun 4. [Google Scholar]
6. Salamanna F, Veronesi F, Maglio M, Della Bella E, Sartori M, Fini M. New and Emerging Strategies in Platelet-Rich Plasma Application in Musculoskeletal Regenerative Procedures: General Overview on Still Open Questions and Outlook. Biomed Res Int. 2015;2015:846045. Epub 2015 May 5. [Pubmed] [Google Scholar]

8. Navani A, Li G, Chrystal J. Platelet Rich Plasma in Musculoskeletal Pathology: A Necessary Rescue or a Lost Cause?. Pain physician. 2017 Mar;20(3):E345. [Pubmed] [Google Scholar]

9. Mazzocca AD, McCarthy MB, Chowaniec DM, Dugdale EM, Hansen D, Cote MP, Bradley JP, Romeo AA, Arciero RA, Beitzel K. The positive effects of different platelet-rich plasma methods on human muscle, bone, and tendon cells. The American journal of sports medicine. 2012 Aug;40(8):1742-9. [Pubmed] [Google Scholar]

10. Mei-Dan O, Carmont MR, Laver L, Mann G, Maffulli N, Nyska M. Platelet-Rich Plasma or Hyaluronate in the management of osteochondral lesions of the talus. Am J Sports Med 2012 40: 534. [Pubmed] [Google Scholar]

11. Mattiello A, Cacciapuoti C. Autologous Platelet Gel Improves Bone Reconstruction of Large Defects in Patients with Bone Giant Cell Tumors. In Vivo. 2015 09-10;29(5):533-540. [Pubmed] [Google Scholar]

12. Dhillon RS, Schwarz EM, Maloney MD. Platelet-rich plasma therapy – future or trend? Arthritis Res Ther. 2012 Aug 8;14(4):219. [Pubmed] [Google Scholar]

13. Harmon KG, Rao AL. The use of platelet-rich plasma in the nonsurgical management of sports injuries: hype or hope? Hematology Am Soc Hematol Educ Program. 2013;2013:620-6. doi: 10.1182/asheducation-2013.1.620. [Pubmed] [Google Scholar]

14 Sakata R, Reddi AH. Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration. Tissue Eng Part B Rev. 2016 Oct;22(5):408-419. Epub 2016 Jun 27.Tissue Eng Part B Rev. 2016 Oct;22(5):408-419. Epub 2016 Jun 27. [Pubmed] [Google Scholar]

15. Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Platelet-rich plasma treatment in symptomatic patients with knee osteoarthritis: preliminary results in a group of active patients. Gobbi A, Karnatzikos G, Mahajan V, Malchira S. Sports Health. 2012 Mar;4(2):162-72. [Pubmed] [Google Scholar]

16. Civinini R, Nistri L, Martini C, Redl B, Ristori G, Innocenti M. Growth factors in the treatment of early osteoarthritis. Clinical Cases in Mineral and Bone Metabolism. 2013;10(1):26-29. doi:10.11138/ccmbm/2013.10.1.026. [Pubmed] [Google Scholar]

17. Dallari D, Stagni C, Rani N, Sabbioni G, Pelotti P, Torricelli P, Tschon M, Giavaresi G. Ultrasound-guided injection of platelet-rich plasma and hyaluronic acid, separately and in combination, for hip osteoarthritis: a randomized controlled study. The American journal of sports medicine. 2016 Mar;44(3):664-71. [Pubmed] [Google Scholar]

18. Rafols C, Monckeberg JE, Numair J, Botello J, Rosales J. Platelet-rich plasma augmentation of arthroscopic hip surgery for femoroacetabular impingement: a prospective study with 24-month follow-up. Arthroscopy: The Journal of Arthroscopic & Related Surgery. 2015 Oct 31;31(10):1886-92. [Pubmed] [Google Scholar]

19. Wu J, Du Z, Lv Y, Zhang J, Xiong W, Wang R, Liu R, Zhang G, Liu Q. A new technique for the treatment of lumbar facet joint syndrome using intra-articular injection with autologous platelet rich plasma. Pain physician. 2016 Nov 1;19(8):617-25. [Pubmed] [Google Scholar]