Platelet Concentration – A Delicate Balancing Act
Regenerative medicine has embraced the platelet rich plasma model as a natural and effective means of stimulating tissue repair. Thousands of articles are currently in the PubMed library and most agree, that platelet rich plasma should be considered one of the first line treatments for a vast array of treatments where regeneration of the tissue is needed.
Why More is Not Always Better in Platelet Therapy
However, the effectiveness of these treatments is simply not a matter of “more is better”. Platelet concentrations in platelet rich plasma, follows a bell-shaped cure, where both excessively high and low concentration can cause diminished efficacy. This leads to some researchers drawing the conclusion that platelet rich plasma does not work or is only mildly effective. There is a delicate balance of platelet concentration in regenerative therapies and further complicating this topic is research showing the paradox of platelet poor plasma showing greater benefit than platelet rich plasma in facial aesthetics and platelet rich plasma at supra-physiologic concentrations showing more benefit in bone regeneration.
Why Platelet Dosing Matters in Regenerative Medicine
There is clinical significance in the number of platelets in platelet rich plasma and not all applications have an optimal platelet dose. Moreover, age can decline platelet numbers, but platelets still work in regenerative therapies in these populations. There are many discrepancies in the field and understanding platelet concentrations can and does improve therapeutic outcomes.
The Misconception of “Higher is Better”
The use of autologous platelet derived products in regenerative medicine has surged over the last decade but the science in platelet concentration is still in active debate. A common misguided concept is that a higher concentration of platelets should yield superior results, yet studies suggest a bell-shaped curve where an optimal middle ground achieves the best results. This becomes a delicate balancing act.
Growth Factor Release and the Bell-Shaped Curve
Platelets release growth factors such as platelet derived growth factor, transforming growth factor-beta and vascular endothelial growth factor, however their effectiveness is concentration dependent. The bell-shaped curve in platelet concentration demonstrates the following;
Low platelet concentrations (Platelet Poor Plasma) still offers regenerative potential in superficial applications and may actually be advantageous as they are low in inflammatory potential.
Moderate platelet concentrations (seen in 3-5 times baseline) show optimal results in soft tissue repair and musculoskeletal applications.
High platelet concentrations (beyond 6-8 times baseline) are beneficial in bone repair but paradoxically inhibit angiogenesis and fibroblastic activity due to excessive growth factor saturation.
Optimal Platelet Rich Plasma Concentration
Current research suggests that the ideal PRP concentration for the majority of regenerative applications lies within the range of 1 million to 1.5 million platelets. This equates to 3 to 5 times the average baseline number in a typical blood sample. This range optimizes growth factor release while avoiding the inhibitory effects associated with excessively high platelet counts. Studies have demonstrated, concentrations within this range enhance cellular proliferation, collagen synthesis and tissue repair making it the optimal ‘sweet spot” for musculoskeletal healing, skin rejuvenation and soft tissue regeneration.
Does PRP Work for Patients with Lower Platelet Counts?
The normal platelet count is 150,000 to 400,000.
Patients with lower platelet counts at baseline such as those around 150,000 can still benefit from PRP therapy as the concentration process increases platelet numbers 3-5 times levels allowing sufficient growth factor release to promote tissue regeneration and healing. Even at lower baseline levels, the proper PRP processing ensures adequate platelet enrichment for therapeutic efficacy. The efficacy is further enhanced with activation, which is a critical step to release growth factors, cytokines and bioactive proteins from the platelets.
The processing devices are paramount in platelet rich plasma therapy to achieve the desired therapeutic outcomes.
The Risk of Over-Concentration in PRP Therapy
Conversely, PRP concentrations exceeding 1.5 million may cause tissue damage due to excessive growth factor saturation, leading to paradoxical effects such as inhibition of angiogenesis, excessive fibrosis and cellular senescence. Over concentration disrupts the natural regenerative balance, emphasizing the importance of achieving the optimal therapeutic range.
What About the Aged Population?
As we age, the platelet counts and function decline. However, platelets still work and do their job in regenerative treatments. Regenerative medicine leverages the platelets to achieve the regenerative potential. Older patients may experience diminished platelet responsiveness, but concentration techniques and activation methods restore the regenerative potential. Despite a natural decrease in platelet efficacy, even aged platelets retain growth factor activity and properly concentrated and activated, the regenerative capability is still efficacious as proven in studies.
Factors Influencing the Bell-Shaped Curve in Platelet Concentrations
Age of the Patient – Older individuals require optimized activation techniques to compensate for a lower baseline platelet count.
Methods of Concentration – Centrifugation and processing methods affect yield and growth factor release.
Number of Treatments and Timing of Applications – Repeated treatments enhance regenerative outcomes depending on tissue exposure. Research has shown the best outcomes come from three applications and not to be treated sooner than 3 weeks apart, so not to cause a hyper-inflammatory state in the tissue.
Kits and Processing Techniques – Commercial PRP kits have many variables such as single or double spin, number of leukocytes in the final product, gel separation or not, anticoagulant used, activation method etc.
Studies
Systematic Review – The Potential Implications of Different Platelet Rich Plasma Concentrations in Regenerative Medicine for Tissue Repair
Int J Mol Sci 2020 Aug 9;21(16):5702 PMID 32784862
This article reviewed 965 articles with 30 of those focusing on PRP concentration.
Conclusion: A PRP concentration of 1 million appears to be optimal, thanks to the constant and plentiful capillary nutrition supply and rapid diffusion of growth factors.
Optimization of Platelet Rich Plasma Concentration for Mesenchymal Stem Cell Applications
Tissue Engineering 17 April 2019 doi.org/10.1089/ten.tes.2018.0091
Conclusion: PRP with 1.5 million was most effective for MSC osteogenic differentiation.
The Optimal Platelet Concentration in Platelet Rich Plasma for Proliferation of Human Cells in Vitro – Diversity, Biases and Possible Basic Experimental Principles for Further Research in the Field: A Review
The Aesthetic and Regenerative Medicine Hub Nov 13, 2020 doi:10.7717/peerj.10303
Conclusion: Optimal PRP concentration for regeneration of tissues is 1 million platelets.
Author’s note: This review was interesting in that it was found that cell type is important in the effect of the PRP concentrations. Fibroblasts from the skin did not respond equally to PRP and PPP, while the same concentration of PRP significantly stimulated the proliferation of fibroblasts from the synovium. The authors concluded cells respond in a dose dependent manner with PRP.
Juventix Regenerative Medical: Leading PRP Innovation
Juventix Regenerative Medical 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 produce a platelet concentrate, devoid of red blood cells with a minimum number of leukocytes that are critical to the regenerative process. Our thixotropic gel separator permits approximately 9% leukocytes to be included in the final concentrate. This amount of white blood cells does not cause a hyper-inflammatory state and has been proven efficacious in thousands of cases.
Although no manufacturer can guarantee the number of platelets in a platelet rich plasma concentrate, Juventix has been lab tested to produce a concentrate that is 4 to 5 times the baseline consistently. Therefore, at average platelet levels, the final platelet amount should be in the middle or surpass the therapeutic regenerative range and fall within the bell-shaped curve for optimal regeneration.
LED Activation and Platelet Rich Fibrin Innovation
Juventix Regenerative Medical offers a patented LED activator to activate the platelets and begin the regenerative process. This activation is a critical step in the release of growth factors, cytokines and bioactive proteins from the alpha granules on the platelets and is accomplished with LED light. This negates the use of chemical additives such as Calcium Chloride, Thrombin or Collagen. This mode of activation by LED light provides sustained growth factor release versus older methods of activation while adhering to the minimal manipulation standards of the FDA. This activation should always be accomplished after the gentle swirl of the centrifuged product to maximize the number of captured platelets.
Juventix Regenerative Medical supplies a patented Bio-Incubator to transform the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The Platelet Rich Fibrin, commonly called the “second generation of platelet products” has different cytokines and growth factors than the original PRP. These different cytokines provide an anti-inflammatory microenvironment and can be used confidently in inflammatory conditions.
Our Commitment to Regenerative Professionals
Juventix Regenerative Medical has a vast array of products, devices and services tailored for the regenerative professional. From Platelet Rich Plasma Kits and processing devices, to our newest additions of microneedling systems to needleless aesthetic treatment devices, Juventix offers the newest “cutting edge” products for our regenerative collaborators. The regenerative marketplace is exploding with technological advancements being added daily for both men and women. With our premier line of products and experienced staff, Juventix will aid and guide any regenerative professional in providing enhanced outcomes and increased patient satisfaction.
RESTORE, REVIVE, REGENERATE – JUVENTIX REGENERATIVE MEDICAL
Regenerative Regards,
Dr. Robert McGrath
