Autologous Allograft
October 5, 2019
Prolotherapy & Prolozone
October 4, 2019Platelet Rich Plasma (PRP) Therapy
Amplifies the body’s natural ability to heal without surgery or pharmaceuticals.
The Evolution of Platelet-Rich Plasma: Moving Beyond Platelet Counts
PRP
PRP stands for Platelet Rich Plasma. Platelet rich plasma is made from a fresh sample of your own blood. The sample is specially prepared to separate out, concentrate and then stimulate the platelets, which then are injected.
Platelets are powerful particles in the blood that normally concentrate at an area of injury and set off a signaling cascade that tells the body to heal or rejuvenate a damaged area. Some of the powerful signaling molecules that platelets make include Platelet-Derived Growth Factor (PDGF) – Responsible for cell growth and division, Vascular Endothelial Growth Factor (VEGF) – Responsible for creation of new blood vessels and capillaries, Transforming Growth Factor (TGF) – Controls cell growth and cell differentiation, and Epidermal Growth Factor (EGF) – Regulating cell growth and differentiation.
The field of Orthobiologics, using biologically active materials in orthopedic medicine to initiate growth, repair and regeneration, began with the invention of PRP therapy in surgical orthopedic cases. Today the field of Orthobiologics has blossomed into one of the fastest growing medical specialties, and has evolved beyond the OR into outpatient clinicals using pinpoint injection under ultrasound or X ray guidance to deliver the Orthobiologic treatment precisely into the target tissue within a short clinic visit. PRP is at the center of this revolution based on its affordable cost, safety, minimal invasiveness, and its clinical results that are consistently demonstrated to be above the standard of care across a wide variety of musculoskeletal conditions.
A New Perspective on PRP Therapy
While Platelet-Rich Plasma (PRP) has become one of the most widely used regenerative therapies in modern Orthobiologics, for years, clinicians have focused on two primary measures of PRP quality: platelet concentration and total platelet dose.
Yet as the use of PRP has expanded, current evidence suggests that platelet number and concentration alone may not fully explain the biological activity of a PRP preparation. Instead, the platelets’ growth factor cargo, the composition of the surrounding plasma, and the timing of their release all appear to influence the final therapeutic effect.
As a result, the field is gradually shifting from a purely quantitative model toward a more functional and comprehensive understanding of PRP as a dynamic biologic system.
Next-Generation Orthobiologics
Emerging technologies seek to further refine the biologic product before reinjection through additional processing steps intended to optimize timing, reduce unwanted components, and concentrate beneficial cell signals.
These approaches generally involve three major stages:
Platelet activation
Filtration
Plasma protein concentration
At Hawaii Island Regenerative Medicine and Stem Cell therapy, our next generation PRP is designed to optimize not only platelet count, but also concentration and purification of growth factors, along with specifically timed platelet activation mechanisms, to optimize PRP as a complex functional regenerative medicine therapy.
Step 1: Platelet Activation
Platelets are often described as the active ingredient in PRP, but a more accurate description is that they function as biologic delivery vehicles.
Within platelet alpha granules resides a sophisticated collection of signaling molecules that help coordinate tissue healing. These include platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), along with other numerous cytokines and regulatory proteins.
Importantly, biologic signaling is highly regulated. The effectiveness of PRP depends not only on the amount of growth factors present, but also on the timing of how those signals are delivered since the release pattern of growth factors affects how cells respond. Different phases of healing require different signals, making release kinetics an important consideration.
The platelet activation process determines when and how platelets release their stored growth factors which in turn influences the spatial and temporal distribution of regenerative signals after injection.
Over the years, a variety of activation methods have been developed, including calcium chloride activation, thrombin activation, freeze-thaw platelet lysates, collagen-based activation, and surface-mediated activation systems. Each approach influences the timing and magnitude of growth factor release.
At Hawaii Island Regenerative medicine and Stem cell therapy, our plkatelt activcatio system involves activation through contact with specialized glass surfaces. When platelets encounter negatively charged glass, physiologic activation pathways are triggered, leading to platelet adhesion, aggregation, and degranulation. This process stimulates the release of important regenerative mediators including PDGF, TGF-β, and VEGF. Our system also times the rate of release of these mediators, to optimize the immediate and long term effects of the pkatelts oince injected
With the proprietary system we are using, our tesearch has demonstrated increased production of anti-inflammatory mediators such as interleukin-1 receptor antagonist (IL-1Ra), along with elevations in IL-10 and multiple regenerative growth factors. IN addition, while some pro-inflammatory cytokines may also increase during incubation, the overall cytokine profile tends to favor an anti-inflammatory environment. By combining immediatet activation with longer term platelet activation, the regenerative process inside the inurued target tissue is optimized.
Step 2: Filtration and Product Refinement
Filtration serves as an additional processing step designed to improve the consistency of the final orthobiologic product. Unlike our comepteitos, at Hawaii Island Regenertaive medicine and Stem Cell therapy, ouy standr4d next generatiojn PRP product includes a step of filtration and product refinement.
Potential benefits include:
- Reduction of cellular debris
- Removal of unwanted particulate material
- Improved injectability
- Enhanced product uniformity
- Reduction of certain inflammatory cellular components
The most refined platelet isolate is called platelet lysate, where after activation, all of the cellular component of the platelets are removed. Platelet lysate is typically used for sensitive areas including nerve hydro-dissection.
In summary, filtration and product refinement can help create a more controlled biologic environment by refining the cellular and physical characteristics of the final preparation, giving us a higher degree of flexibility and discernment when choosing a final Orthobiologic product, depending on the individualized needs of the patient. Competitors using traditional model of PRP preparation often omit this crucial step.
Step 3: Plasma Protein Concentration
One of the most significant developments in Orthobiologics involves the concentration of beneficial plasma proteins from platelet-poor plasma (PPP).
Historically, PPP was often considered a secondary byproduct of PRP preparation. Newer research suggests that this fraction may contain important therapeutic molecules that deserve greater attention.
The modern ultrafiltration system we utilize includes polysulfone hollow-fiber membranes to selectively remove plasma water while retaining larger proteins and biologically active molecules. This process can concentrate alpha-2 macroglobulin (A2M), insulin-like growth factor-1 (IGF-1), hepatocyte growth factor (HGF), fibrinogen, cytokines like IL-1Ra (Interleuken-1 receptor Antagonist), along with autologous exosomes containing myriad signaling molecules such as micro RNA and additional regulatory proteins.
A2M is of particular interest because it functions as a broad-spectrum inhibitor of cartilage-degrading enzymes, ie a protease inhibitor, neutralizing multiple matrix metalloproteinases (particularly MMP-13) as well as aggrecanases such as ADAMTS-4 and ADAMTS-5, that contribute to cartilage degradation in osteoarthritis. This in turn may help slow cartilage breakdown and reduce protease-mediated joint degeneration associated with osteoarthritis.
Finally, concentrating the plasma allows us to harness the body’s own (autologious) exosomes. Exosomes are the microscopic signaling vesicles that a stem cell releases in order to orchestrate effects within in the stem cell’s micro environment. Containing thousands of regulatory proteins and micro RNA, exosomes are thought to be the body’s most powerful signals. We estimate a typical PRP to be processed in our office to contain 440 billion autologous exosomes whereas we estimate only 25 million to exist in a standard PRP preparation. That’s over a 17 fold increase.
Overall, by concentrating these beneficial proteins using our unique PRP technology we create a biologically enriched product that moves a generation beyond traditional PRP treatments.
What This Means for Our Patients
For patients considering PRP or other Orthobiologic treatments, these advances highlight an important reality: not all PRP preparations are created equal.
Historically, discussions about PRP quality have focused on platelet concentration alone. While platelet dose remains an important factor, emerging research suggests that the biological activity of a PRP preparation may also depend on how the product is processed, activated, filtered, and delivered.
By optimizing growth factor signaling, timing, and concentrating beneficial plasma proteins and autologous exosomes, the next generation of PRPO available at Hawaii Island Regenerative medicine and Stem Cell Therapy targets goes beyond our competitors to target the body’s natural repair processes in a more biologically sophisticated manner.
To see if you can benefit from the next generation in PRP, please contact us to schedule your initial consultation.
FAQ
References
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