Knowing how to dose orthobiologics, like PRP, is critical. However, we have very little published data, and physicians use different machines that produce different types of PRP at different doses. So to say that orthobiologics as a field is one big mess is an understatement. The Regenexx research team has been working to clean up that mess for many years. Our most recent entry in that effort is a new tendon PRP research paper on tendons and PRP dosing.
Why Spend This Money?
Very few orthobiologics companies spend money on research. Even fewer physician networks even have lab research capabilities in the first place, and none so far have spent their own money on lab research to support correct dosing. For Regenexx, publishing this most recent paper cost six figures in hard costs for lab items, employee time, and my time. Why do this?
As someone once said, it’s lead, follow, or get out of the way. This paper is all about leading the orthobiologics space. In this case, there was confusion on how to properly dose tendon injuries with platelet-rich plasma. Some papers went one way, and other papers (which were poorly done) went the other direction. So there needed to be a well-done tiebreaker paper that sided with one or the other approach.
What Is PRP?
Platelet-rich plasma (PRP) is made by taking a blood sample from the patient and concentrating the platelets in that blood. Platelets contain many helpful growth factors that can act like an espresso shot for the local repair cells that help heal damage. There are different types of PRP, and of those commonly injected, there is leukocyte-rich (red) and leukocyte-poor (amber).
Approaches to PRP Dosing
The problem with bedside PRP machines is that they generally are only validated to produce one type of PRP and at one dose. In PRP shots, the dose is commonly reported as either a certain number of platelets or a times concentration over baseline. More platelets in the PRP have more growth factors and thus should, at face value, produce better clinical results.
The issue of “more is better” in PRP dosing has been hotly debated for years. The problem is that what often enters into the equation are white papers and other lower-level research investigations pushed by manufacturers of specific machines that all seem to show that whatever that machine produces is the best thing since sliced bread. This is because the manufacturers of these machines are often locked into producing only one type and dose of PRP.
We at Regenexx have always used a flexible lab platform, which means that we can produce any type or concentration of PRP. So our guidelines for dosing have always been driven by what we see in the lab. For example, we noticed early on that higher platelet concentrations sparked more growth in older mesenchymal stem cells (MSCs) in culture. This was the case for older cells, with younger cells tending to max out their proliferation at lower PRP doses. Hence, we have always used higher PRP doses in older patients.
Is High or Low Concentration Better for Tendons?
Based on our experience with MSCs in culture, we have always gone with higher doses in tendon injections to treat tears or degeneration (tendinopathy). The literature generally supported that approach until a paper was published that seemed to show that higher PRP doses in tendons caused less and not more tendon cell healing. The results of this paper generally didn’t fit with what we saw clinically. Why? Many of our tendon injury patients were doing well getting very high-dose platelet injections. So we dug into the new paper, and our scientific team saw a fatal flaw. To understand what that was, see my video below:
Our New Tendon PRP Research
In our new study, we took human tendon cells (tenocytes) and tested both their growth rate (proliferation) and ability to close an experimental wound (scratch test) relative to the dose of platelets used. We also used older tendon cells because older patients typically present to us with tendinopathy. We also fixed the experimental design flaws of the paper discussed above. What did we find?
There is a direct dose-response relationship. This means the higher we went on platelet dose the more tendon cell proliferation we saw and the better the cells were at healing the experimental wound. This fits well with our prior observations.
Why do we see a direct dose-response with old cells, and young cells tend to max out their activity with lower platelet doses? It’s likely that old cells, which live in a growth factor (GF) poor environment, have more GF receptors on their surfaces to take advantage of their world. When we then put in higher GF levels with more platelets, these older cells have more receptor hits; hence, the cells are more stimulated.
The upshot? At the end of the day, at Regenexx we lead orthobiologics, even if that means spending lots of our own money to figure out the likely best dose for tendons and to correct the scientific record after a poorly constructed study is published. Again, it’s lead, follow, or get out of the way!