Arthrex, Platelet-Rich Plasma, PRP

PRP Hair Loss Treatment Variation

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I last updated my main platelet-rich plasma post (does PRP work for hair loss) in 2020. In there, I list over 50 studies that support the benefits of PRP scalp injections for hair growth.

I have written many other posts on platelet-rich plasma. Among the highlights include: a summary of key growth factors in PRP; rare instances of hair darkening; and Dr. John Cole’s interesting experiments with activated and sonicated PRP.

However, most readers are justifiably very skeptical about platelet-rich plasma. We see very few positive testimonials and reviews on hair loss forums, while studies suggest otherwise. One possible reason is that the methods used for PRP treatments are all over the place and impact success rates significantly.

Doctors who are totally inexperienced with hair loss treatments often start injecting PRP into patient scalps without any training. Many use the cheapest possible centrifuges and never even try to measure platelet counts.

In this post, I attempt to describe platelet-rich plasma treatment methodologies used by various leading hair transplant surgeons. Note that some physicians often combine PRP treatments with one or more of: ACell, exosomes and microneedling.

Update: December 2022

Two patients in Croatia got great platelet-rich plasma hair growth results via a novel protocol. Make sure to check out both the before and after photos. Each received an initial injection that contained a large volume of concentrated PRP (cPRP) solution activated by calcium (via the Arthrex Angel System). this was followed by a second, small-volume booster without activation. The Arthrex Angel System achieves a high concentration of thrombocyte cells.

PRP Hair Growth Treatment: Platelets per Microliter

  • Perhaps the most experienced doctor in the US when it comes to using platelet-rich plasma for hair growth is Dr. Joseph Greco. I have covered him a few times. Besides using PRP, he also uses a purified version of PRP called CRP (Cytokine Rich Plasma). See this chart on his site for a comparison of differences between the two.
  • Dr. John Cole who I mentioned earlier is also among the most experienced American physicians when it comes to using PRP for hair growth. Dr. Cole also uses CRP. On his site, he has a very interesting article section titled “Dr. Cole discusses differences in PRP.” He notes that most PRP kits in use today lack when it comes to ultimate platelet concentrations and platelet yields. In his opinion, the best benefit for hair growth comes at platelet-rich plasma concentration levels of 1 million platelets per milliliter.
  • Dr. Cole uses a Hemoccult machine that uses light to differentiate cells and quantify them accurately. One interesting thing that Dr. Cole told me was that “What I can tell you for sure on platelet-rich plasma is that you want a reddish PRP. Not a yellow PRP. The best and youngest platelets are on the surface of the red cells. Hence, you want a little flash of red in the final spin to capture those platelets.”
  • Dr. Joseph Yaker shared with me an interesting series of slides he made for a presentation on the need to standardize PRP dosing. Since 2018, he has been using the TruDose™ system at his practice for platelet-rich plasma dosing accuracy. Dr. Yaker offers his own version of platelet-rich plasma called Precision PRP™️.
PRP Treatment
PRP hair loss treatment using the TruDose™ system.
  • The foremost expert on platelet-rich plasma for hair growth in the world might be Dr. Pietro Gentile from Italy. Especially when it comes to number of study publications. Dr. Yaker in his aforementioned slides mentioned a 2015 study from Dr. Pietro Gentile that found an ideal PRP dosage of 1.5 million platelets per microliter. The exact quote from this study:

“A mean of 1,484,555.6 platelets per microliter in the PRP preparation could effectively stimulate follicular and perifollicular angiogenesis (blood vessel formation), which is suggested to be one of the major factors in active hair growth.”

  • Another leading US based hair transplant surgeon Dr. Aron Nusbaum published a study in 2018 titled: “Examining the Variability of PRP with Different Preparation Systems.” Him and his partner found that the concentration of platelets produced by four different commercially available systems demonstrated wide variance. Also, while most systems only require blood collection of 15-22cc, the Arthrex System uses over 120ml of blood. Dr. Nusbaum told me that his clinic uses the Angel System by Arthrex. They found this device leads to the highest platelet concentration. He also adds ACell during the procedure, and they recommend PRP treatments every 6 months.
  • Dr. Jerry Cooley is yet another highly experienced platelet-rich user. In one of his past comments he stated the following:

“There a lot of different ways to ‘do’ PRP. Adding ACell is just one variable. Some of these other variables are: the device used to centrifuge the blood; the concentration of platelets achieved; the total volume injected; the size of the syringe and needle used to do the injecting; the depth level in the scalp it is injected; whether the PRP is ‘activated’ or not; the use of microneedling; etc. All of these can affect the result in my opinion.”

Make sure to see Hair Transplant Mentor Joe Tillman’s video of his platelet-rich plasma treatment with Dr. Cooley in 2016.

Activated versus Non-Activated

Many researchers recommend differentiating between autologous activated versus non-activated platelet-rich plasma. The former entails “activation” to induce growth factor secretion via the addition of calcium gluconate (or sometimes calcium chloride or thrombin). In the above video, Dr. Cooley injects calcium thrombin during the activation process.

A new January 2022 paper titled “Lasers, lights, and compounds for hair loss in aesthetics” contains a detailed section on platelet-rich plasma. It includes a discussion of autologous activated PRP (AA-PRP) versus non-activated autologous PRP (NA-PRP). The full version of the paper can be read via Sci-Hub (whose link keeps changing, so I am not posting here).

Among the most relevant quotes in this paper:

“The number of centrifugations, revolutionary speed, and spin time can affect platelet activity, degranulation, and growth factor viability. For example, longer or faster spin cycles more effectively separate the erythrocytes, buffy coat, and plasma, but this may also damage platelets and cause premature release of growth factors.”

“Preparation parameters should include the presence or absence of an anticoagulant, volume of blood drawn, presence or absence of leukocytes, spin method (speed and duration), activator used, and fraction of plasma collected. Authors should also report the mean platelet concentration, total volume, and volume per area used in treatment. This level of detail will allow for improved standardization that can be applied to real-world dermatology practice.”

Leukocytes and Fibrin Matrix

A proposed classification system that the above paper outlines would break out platelet-rich plasma into five categories:

  1. Pure or leukocyte-poor PRP (P-PRP).
  2. Leukocyte-rich PRP (L-PRP).
  3. Leukocyte-poor platelet-rich fibrin matrix (P-PRF).
  4. Platelet-rich fibrin matrix (PRFM),
  5. Leukocyte-rich fibrin and platelet-rich fibrin (L-PRF).
Dermal Papilla Cells, Maksim Plikus, SCUBE3

SCUBE3 Signaling Molecule for Hair Growth

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I have covered Dr. Maksim Plikus a few times on this blog in the past. I have also discussed Hedgehog signaling and hair growth in detail. Yesterday, a University of California team (led by Dr. Plikus) discovered a critical signaling molecule SCUBE3 that stimulates hair growth.

Update: March 27, 2023

In a new interview with UCI, Dr. Plikus states that:

“SCUBE3 would be microinjected less than a millimeter beneath a person’s skin. It would be a fairly painless process that would have to be repeated periodically to maintain hair growth.”

Update: July 29, 2022

Yet another update just came out (h/t “YoYo”). I like the phrase “digitize the hair“.

Update: July 18, 2022

New video titled: “UC Irvine scientists discover a possible cure for baldness.” Starring Dr. Maksim Plikus (h/t “YoYo”). And yet another one.

Update: July 7, 2022

Dr. William Rassman provided an update on Reddit on July 7:

SCUBE3 Signaling Molecule Trials via Amplifica
Amplifica is a biotechnology company that was co-founded by Maksim Plikus and Dr. William Rassman. They plan to begin SCUBE3 clinical trials by the end of 2022.

SCUBE3 represents one part of the interconnected hair growth loop that also includes the hedgehog pathway, dermal papilla cells, TGF-β and Wnt5a. This interaction is shown in the below diagram from this latest research.

SCUBE3 Hair Growth
SCUBE3 signaling molecule stimulates hair growth. Source: Development Cell.

July 1, 2022

SCUBE3 Signaling Molecule Stimulates Hair Growth

University of California, Irvine (UCI) led researchers have discovered that a signaling molecule (which they call SCUBE3) potently stimulates hair growth. Most importantly, it may offer a therapeutic treatment for androgenetic alopecia, which accounts for 90-95 percent of hair loss cases in both men and women.

The actual study was published yesterday in Development Cell. The study team included health professionals and academics from UCI, San Diego, China, Japan, Korea and Taiwan.

“UCI has filed a provisional patent application on the use of SCUBE3 and its related molecular compounds for hair growth stimulation.”

This study discovered the precise mechanism by which the dermal papilla cells (fibroblasts at the bottom of each hair follicle) promote new growth. According to Dr. Plikus:

“We revealed that the SCUBE3 signaling molecule, which dermal papilla cells produce naturally, is the messenger used to ‘tell’ the neighboring hair stem cells to start dividing, which heralds the onset of new hair growth.”

In people with androgenetic alopecia, dermal papilla cells start to malfunction. One of the reasons behind this is a major reduction in the normally abundant signaling and activating molecules. It seems like SCUBE3 protein microinjections are sufficient to induce new hair growth.

However, note that mice were involved in this initial work. The research team microinjected SCUBE3 into mouse skin in which human scalp follicles had been transplanted. This induced new growth in both the dormant human hair follicles and surrounding mouse follicles due to “hyperactivated” dermal papilla cells.

Per co-first author and UCI postdoctoral researcher Christian Guerrero-Juarez, these experiments provide proof that SCUBE3 or derived molecules can be a promising therapeutic for hair loss.

According to Dr. Plikus, there is a strong need for new, effective hair loss medications. Naturally occurring compounds that are used by dermal papilla cells for hair growth “present ideal next-generation” candidates for pattern baldness treatment.

More detailed research on this subject will be conducted in the Plikus Lab and at Amplifica Holdings Group. The latter is a biotechnology company that was co-founded by Plikus and includes Dr. William Rassman on its team. For more on that company, see my post on Amplifica and its hairy moles treatment for baldness.