How to Evaluate PRP Research - The Good, The Bad, The Ugly

Updated: Dec 5, 2021

PRP has emerged as one of the most promising and highly researched interventions in treating muscle and soft tissue injuries. While this is a positive for the industry and anyone invested in the progression of regenerative medicine, it also means that for every good piece of research on PRP, there will undoubtedly be some bad ones, and some even uglier ones.

In the past month, we've seen two of the worst PRP studies published in recent memory. Unfortunately, these are representative of a weakness in modern PRP research.

Why? Because at face value, the papers actually appear to have a good study design and received the rubber-stamp of publication by the reputable journal, JAMA. So what makes them bad PRP studies? Well, because they used ineffective PRP.

The Good - Best Practices in PRP

In 2004, Marx determined that the minimum concentration needed for PRP to be called Platelet-Rich was > 4x above baseline (2). Interpreted another way, anything BELOW this threshold is NOT considered PRP based on its inability to drive optimal regeneration of tissue. Over the years, numerous studies have emerged that support this threshold both in vitro and in-vivo (2-4). Despite this, there are still many commercial systems sold and used by clinicians that cannot produce PRP by this definition:

In 2018, Adrian Le et al. sought to further evaluate PRP research beyond concentration and characterize best practices based on the type of PRP used (LR- or LP-PRP), frequency of dose, etc. (4). Taking knee OA for example, they found an abundance of level l studies available for analysis:

13 of the 16 studies available showed a clinical benefit to PRP over the control - that's an 81% effective rate in aggregate. The success of these trials was dependent on choosing the correct type of PRP to drive positive results - namely platelet dose (i.e. concentration) and presence (or absence) of white blood cells. We dug into each of these papers further to determine how you can apply these learnings to your practice, here and here.

The key takeaway is that not all PRP is created equally. Our understanding of what effective PRP looks like is growing and perhaps more notably, what ineffective PRP looks like.

The Bad and the Ugly

Now back to the studies in question, specifically, the RESTORE trial that evaluated PRP for knee osteoarthritis (OA) and another RCT that looked at PRP for ankle OA (5,6). In both cases, authors concluded that PRP had no therapeutic effect over the control - a significant divergence from established evidence.

When you dig into these trials and their method of PRP preparation, we find that the RESTORE trial used a PRP system from Arthex (Arthrex ACP) that independent studies have verified to routinely concentrate the product to a whole 1.3x above baseline (7). In the ankle trial, authors used an even more ineffective product in RegenLab PRP, which concentrates product to only 1.2x above baseline (7). Suffice to say, neither of these products are even PRP so it's no surprise they did not find any improvement.

This is not the first time we've seen studies such as these make the rounds on social media by the "told you so" community of PRP skeptics. In 2017, Brian Cole et al. found no improvement over control with the use of PRP for knee OA (5). His PRP of choice? You guessed it, Arthrex ACP that was measured at ~1.7x above baseline!

So why do authors publish these papers and clinicians buy these products? Well, because the products are cheap and the users may not be properly informed of the impact these products can have on their patient outcomes. Or, perhaps there are other stakeholders involved that stand to benefit from slowing the rapid adoption of PRP.

What's the Bottom Line?

If you are a stakeholder in regenerative medicine (patient, practitioner, researcher), you need to understand industry best practices. At the very least, you should be asking about platelet dose (or concentration above baseline) and the method of PRP preparation. You would be surprised to find that in many cases, clinicians are not even using PRP and therefore doing harm to patients and the industry as a whole.

What did we really learn from these studies? That ineffective PRP systems are still prevalent and present a risk to your patients treatment success - they just don't work. If you want to stack the deck in your favour, MDBiologix and our 20 years of experience in regenerative medicine can help you make the best decision for your practice and patients.


  1. Marx, RE. Platelet-Rich Plasma: Evidence to support its use. J Oral Maxillofac Surg 2004; 62:489-496.

  2. Gentile P, Garcovich, S. Systematic Review—The Potential Implications of Different Platelet-Rich Plasma (PRP) Concentrations in Regenerative Medicine for Tissue Repair. Intl J Mol Sci. 2020.

  3. Yaradilmis YU, Demirkale I, Safa Tagral A, Caner Okkaoglu M, Ates A, Altay M. Comparison of two platelet rich plasma formulations with viscosupplementation in treatment of moderate grade gonarthrosis: A prospective randomized controlled study. J Orthop. 2020 Jan 28;20:240-246. doi: 10.1016/j.jor.2020.01.041. PMID: 32071523; PMCID: PMC7011002.

  4. Le A, Enweze L, DeBraun M, Dragoo J. Current Clinical Recommendations for Use of Platelet-Rich Plasma. Current Reviews in Musculoskeletal Medicine. 2018. 11. 10.1007/s12178-018-9527-7.

  5. Bennell KL, Paterson KL, Metcalf BR, et al. Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial. JAMA. 2021;326(20):2021–2030. doi:10.1001/jama.2021.19415

  6. Paget LDA, Reurink G, de Vos RJ, Weir A, Moen MH, Bierma-Zeinstra SMA, Stufkens SAS, Kerkhoffs GMMJ, Tol JL; PRIMA Study Group. Effect of Platelet-Rich Plasma Injections vs Placebo on Ankle Symptoms and Function in Patients With Ankle Osteoarthritis: A Randomized Clinical Trial. JAMA. 2021 Oct 26;326(16):1595-1605. doi: 10.1001/jama.2021.16602. PMID: 34698782.

  7. Magalon J, Bausset O, Serratrice N, et al. Characterization and comparison of 5 platelet-rich plasma preparations in a single-donor model. Arthroscopy 2014; 30(5):629–38.

  8. Cole B, Karas V, Hussey K, Pilz K, Fortier L. Hyaluronic Acid Versus Platelet-Rich Plasma: A prospective, double-blind randomized controlled trial comparing clinical outcomes and effects on intra-articular biology for the treatment of knee OA. Am J Sports Medicine. 2017. 45(2):339-346.