Introduction

There is a saying that goes, "We are our own best doctors." This is because the human body has a natural and spontaneousself-healing system that allows us to maintain a state of health and avoid losing vitality from external factors such as physical, chemical, and microbial invasions. The self-healing system includes several subsystems such as the immune system, stress system, repair system, endocrine system, and others. When any of these subsystems experiences functional or coordination disorders or encounters external factors that cause damage, the self-healing ability produced by the self-healing system will inevitably decrease, resulting in pathological or sub-healthy states in the organism. Medicine usually cannot directly eliminate symptoms, but it can promote the function of the self-healing system by supplementing the missing elements in the body, thereby achieving the goal of curing the disease. Therefore, modern medicine exists to assist the body's self-healing system in treating diseases.

Hemostasis

There is a very intuitive example about the human body's self-healing ability: when we sustain injuries such as cuts and bleeding, we usually can heal ourselves automatically after a period. This is common knowledge that everyone has. However, the mechanisms underlying this process are not well understood by many. So how does this process actually work？

Step 1: When the human body is injured and the skin is broken, bleeding occurs, which also means that the blood vessels have been damaged. Damage to cells in the blood vessel wall releases chemicals that begin the process of blood clotting.

Step 2: The released chemicals initiate a chain reaction, causing platelets to adhere to the outer side of the cut blood vessel and change shape (activation), bridge to each other (aggregation), and ultimately form a platelet plug. Meanwhile, activated clotting factors convert prothrombin to thrombin, which then converts soluble fibrinogen to insoluble fibrin. Fibrin forms a mesh-like structure, which acts to stabilize the blood clot. The clotting mechanism interacts with other hemostatic mechanisms, especially those involved in the formation of platelet plug, to produce a clot.

Step 3: During the formation of the clot, new releases of the chemicals occur, leading to further acceleration of the clotting process. This is referred to as a "positive feedback loop of clotting acceleration." Ultimately, when enough clotting has occurred, the damaged blood vessel wall is repaired. This is the reason why wounds can be rapidly stopped from bleeding in a very short time

Regeneration

During this process, (a) after the wound stops bleeding, there will be the onset of (b) inflammation, which will naturally disappear as (c) cells proliferate. Eventually, with the production of collagen fiber cells, (d) the reshaping of cells is completed, which is the entire process of wound regeneration (self-healing).

Growth factors

There are several key points worth noting in the above-mentioned self-healing process. First, when bleeding occurs, platelets will aggregate and release growth factors. Growth factors are a type of protein molecule that stimulates cell proliferation and differentiation in the human body, serving as a signaling role. Once the signal is sent out by the growth factors, the human body automatically produces various types of fibroblasts. When these fibroblasts are produced, they not only begin to repair tissues, but also eliminate inflammation. When these fibroblasts are produced and functioning, the human body will continuously produce more fibroblasts to support the healing process in a positive feedback loop until the entire "regeneration" (self-healing) process is complete with the production of collagen fibers.

The utilization and research of human body regeneration mechanism

With the continuous improvement of the understanding and principles of the human body's self-healing mechanism, many medical experts have proposed questions like: whether we can use this natural mechanism to obtain a safe solution to the cell regeneration problems inside the body? Can we use the restoration of certain human tissues to treat diseases caused by the loss or decline of self-regeneration ability due to aging or other reasons?

The discussion range of these questions extends from solving painful (injury or inflammation) conditions in different parts of the body to postoperative repair, and to attempt to resist the signs of aging that were once considered irreversible in the human body, and further to the pathogenicity of some chronic diseases.

Currently, treatment methods that utilize the human body's regeneration mechanism have been successfully applied to various clinical cases worldwide, ranging from more intuitive technical applications such as dental and skin tissue repair after specialized surgeries, to discussions in various fields such as bone pain (osteomyelitis , cervical spondylosis, lumbar spondylosis, osteoarthritis, sports injuries), skin beauty (anti-aging, repair, spot removal, hair growth), and chronic skin diseases (diabetic foot, bedsores).

At the same time, the exploration of new fields has never stopped. For example, whether applying related treatments to human neural tissues can cure health problems caused by degenerative neural diseases, such as the increasing problem of insomnia that many people are facing.

PRP (Platelet - rich plasma)

The first generation of products inspired by the human body's regenerative (self-healing) mechanism at the end of the last century is called PRP. Its principle is to extract a super-physiological dose of growth factors from human blood and inject it at the site of the injury, using the signaling mechanism of the body's self-healing mechanism to stimulate the production of fibroblasts needed for tissue repair to induce faster wound healing

Since growth factors are mainly concentrated within platelets in human blood, the extraction process is not complicated. First, blood needs to be extracted from the patient and placed in a centrifuge. It is then spun at a certain angle and speed, and particles of different weights in the blood will sink or float under the influence of gravity, forming layers of different colors. Among them, the heavier red blood cells will sink, and the lightest serum will float to the top, while blood platelets, white blood cells, and fibrin, which are of similar weight, will aggregate in the middle layer, which is the part that needs to be extracted for PRP.

For a long time, the emergence of PRP technology as a new treatment method has promoted the healing of skin wounds on the body surface faster than other treatment methods, and has provided the possibility of using autologous blood cell therapy to directly target human body lesions. We already know that the first problem that the body's self-regeneration (self-healing) mechanism needs to solve is how to "send signals" to the body. Only when bleeding occurs and the concentration of platelets in the blood locally increases sharply, the body will produce signals. The reason why the lesions in the body cannot regenerate (self-heal) for a long time is precisely because the relevant lesions do not produce a large number of platelet aggregates, send signals, and produce "positive feedback". PRP technology solves this problem of "sending signals" with the simplest thinking, which is a very direct small step, but it opens the door to a new treatment concept. This treatment technology was once popular all over the world, especially in the treatment of sports injuries. Even today, due to its earlier discovery and use, there are quite a lot of literature and case contributions at home and abroad. After a lot of data accumulation and several upgrades and improvements, it has gradually been widely accepted and used by mainstream hospitals and medical institutions.

Currently, there are three main problems with PRP technology, mainly due to the complicated preparation process of PRP and the use of chemical additives during preparation.

The first problem is that during the preparation process of PRP, blood coagulates rapidly at normal temperature after leaving the human body, making it impossible to centrifuge and obtain PRP.

To solve this problem, the PRP commonly used in the market during the entire preparation process usually involves storing blood in tubes with added anticoagulants (such as sodium citrate and heparin). When separating platelets using a centrifuge, two centrifugation steps are required, and the total separation time takes approximately 30 minutes.

The second problem arises as clinical research deepens, due to the addition of anticoagulants during the preparation of PRP. After injecting PRP into the lesion, it is quickly diluted by the body. Although PRP is rich in high concentrations of platelets, the duration of stay is not long enough to sustain "signal release" to stimulate continuous cell regeneration, resulting in unsatisfactory effects. Therefore, a significant proportion of early PRP cases have been found to be ineffective after comparative observation. Scientists have analyzed and found that the PRP extract lacks fibrous protein adhesive agents necessary for the "positive feedback loop" during the human body's regeneration (self-healing) process.

To solve this problem, the upgraded generation of BRP technology adds thrombin and calcium to PRP after separation and before injection back into the human body. This technique is called Fibrin technologies in clinical surgery, and it is believed that the biochemical characteristics of surgical additives are a necessary condition to ensure the effectiveness of PRP treatment. Moreover, the "3-dimensional fibrin architecture" heavily relies on the clinically polymerized process after artificial intervention, such as the use of a large amount of bovine thrombin addition. The expected result after injection is to achieve a longer duration of stay and strengthen the treatment effect.

The third problem is that to solve the first and second problems, chemical additives such as anticoagulants and thrombin must be added to PRP during the entire preparation and injection process. As it enters the human body, some hidden risks exist, namely the body's "rejection" characteristics of non-endogenous substances. Rejection not only makes it impossible for PRP to achieve the expected effect in the body but also increases the possibility of postoperative allergic reactions and even the possibility of acquired coagulation disorders and other diseases caused by the added chemical additives. Due to the large individual differences in the human body, it is difficult to accurately predict and control these side effects.Academia has raised concerns about this risk: "Although fibrin glue has a good track record in many field-related schemes over the past 30 years, it remains controversial due to the complexity of production schemes (compared to autologous adhesives) or the risk of cross-infection (for commercial adhesives)." (Dohan et al., 2006)

In essence, although PRP is a groundbreaking technology that takes a crucial step in utilizing the human body's self-healing mechanism to help humans overcome pain and illness, it is not a perfect "safe" treatment technology in the eyes of scientists and medical professionals. There are still some areas where the treatment effect falls short of satisfying both medical professionals and patients.

PRF（Platelet-rich fibrin）：

As the new century arrived, the biggest weakness of PRP technology remained unsolved. In order to improve treatment safety, the medical community needed an upgraded treatment option that could obtain PRP or even better components without adding any "non-autologous" additives. With the efforts of scientists and medical professionals, a new technique called "second-generation platelet concentrate" was discovered and introduced into clinical practice.

In this new technique, Platelet-rich fibrin (PRF) was discovered as an upgraded version of Platelet-rich plasma (PRP) technology. The centrifuge parameters were updated and adjusted in the preparation process, allowing for a faster and shorter centrifugation and separation time without the use of any anticoagulants or other additives. At the same time, fibrin and white blood cells in the blood were effectively retained. Due to the lack of inhibition of the clotting process, the PRF extract quickly formed into a gel.

Compared to PRP, this new discovery has two significant advantages:

First, no chemical or other living additives are added during the preparation process, significantly reducing the risk.

Second, PRF contains more "fibrin" than PRP, making up for the deficiency of autologous adhesives in PRP. When PRF is injected into the body tissue, not only do the platelets obtain a scaffold to rely on, but the PRF, rich in fibrin, can stay and act in the affected area for a longer time, continuously sending healing signals to the body, promoting positive circulation. In comparative treatment effectiveness, PRP often has short-term and immediate effects, unable to release healing signals for a long time, resulting in limited therapeutic effects. PRF can extend the action time of signal factors to 5-10 days, significantly improving the therapeutic effect of this self-healing technique.

In the above figure, we can see the schematic diagram of the matrix and cellular structure of four types of platelet concentrates very intuitively. Two key parameters are important: white blood cell content (blue spheres), fibrin density (light brown fibrous lines), and platelet aggregates (light gray shapes) always attach to fibrin. In typical P-PRP and L-PRP preparations, the fibrin network is thin, fragile, and immature. Although composed of fibers, this fibrin network dissolves rapidly like fibrin glue due to simple fiber polymerization and small diameter (red arrows). Although this fibrin network supports platelet application during surgery, it is quickly dissolved. In P-PRF and L-PRF preparations, the fibrin is thicker and sturdier (black arrows) and constitutes a resistant matrix due to the assembly of multiple fibers, which can be considered as a fibrin biological material.

In clinical practice, the "safety" of PRF itself is beyond doubt. Because no non-human-derived additives are used in the preparation of the entire PRF technology, the possibility of rejection reactions or cross-infection during surgery is eliminated, and the postoperative efficacy has made greater progress compared to PRP.

However, PRF technology also has its limitations. First, the preparation time and surgery time must be very short after the blood leaves the body, otherwise, the PRF will turn into a gel within a limited time. This means several problems:

The first problem is that the clotting of blood into a gel means that PRF cannot be injected into deeper tissues, and the treatment range is limited to the surface of the skin. Although solid PRF has medical value in the treatment of postoperative dental repairs or other auxiliary treatments for surface wounds, its use is greatly discounted compared to PRP.

The second problem is that the poor injectability of PRF means that doctors need to use thicker needles to inject patients. Using thick needles may cause additional damage to human tissue when entering the body, bringing new risks, while patients will face greater pain. In some treatments, even anesthesia may be applied to the patient's injection site before PRF injection. This once again uses non-human-derived additives, which reduces the safety that has already been improved, creating a kind of reverse effect.

Summary:

With the efforts of medical researchers and advancements in technology, there has been significant progress in harnessing the human body's self-healing system. The evolution from the first-generation technique PRP to PRF has addressed concerns such as increased surgical risks due to anticoagulants and suboptimal treatment outcomes. However, PRF still has limitations, including the inability to prevent blood clotting, resulting in compressed surgical time. These limitations have restricted the application of PRF in certain areas. Therefore, UCHON aspires to address the unresolved challenges and difficulties in self-regeneration therapy, aiming to further enhance this beneficial treatment technique for humanity.

Reference:

Dohan, D. M., Choukroun, J., Diss, A., Dohan, S. L., Dohan, A. J., Mouhyi, J., & Gogly, B. (2006). Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 101(3), e37-e44.

Ehrenfest, D. M. D., Rasmusson, L., & Albrektsson, T. (2009). Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte-and platelet-rich fibrin (L-PRF). Trends in biotechnology, 27(3), 158-167.

Newest Generation Technology: PA-PRF (Physical Anticoagulant Platelet Rich Fibrin)

After nearly a decade of technological evolution and development, the broad PRP/PRF technology is increasingly being used by more medical experts in different treatment fields. Academic research and discussions have continuously optimized the clinical application of medical technology, while medical technology continues to iterate.

With the advent of the new generation PA-PRF technology, we no longer need to worry about the rapid coagulation of blood during the preparation process, which severely limits the surgical time. The patented technology of Physical Anticoagulant Platelet Rich Fibrin (PA-PRF) makes the entire process of PRF preparation from blood sample collection to the final surgery effortless. Traditional PRP technology has gradually lost its luster since the moment of finding a more advanced PRP preparation scheme that requires no chemical additives, non-autologous biological anticoagulants, and thrombin.

The Physical Anticoagulant Platelet Rich Fibrin (PA-PRF) system, personally developed and designed by Dr. Zhai Yue, the founder of UCHON, has obtained multiple national invention patents and utility model patents, filling several gaps in China's research on human self-healing therapies. The principle is not difficult to understand: research has shown that the key factor causing blood coagulation, thrombin, is most active at 37 degrees Celsius, and once the temperature drops below 10 degrees Celsius, its activity will be significantly reduced. In the PA-PRF technology, the process of blood extraction and centrifugation is strictly limited to a low-temperature environment, which reduces the activity of thrombin and delays the coagulation of blood. At the same time, the three-minute preset centrifugation setting can stably separate the extract under specific speed conditions. This technology not only retains the platelets in traditional PRP technology but also protects the fibrin that would be destroyed in traditional PRP preparation due to the addition of anticoagulants, as well as enriches the concentration of regenerative factors and white blood cells (concentration can reach more than twice that of normal blood). Meanwhile, the Physical Anticoagulant Platelet Rich Fibrin (PA-PRF) can maintain a liquid state without the addition of anticoagulants for more than 30 minutes, providing doctors with more abundant surgical time. From the perspective of maintaining liquid stability, the extract prepared by our Physical Anticoagulant Platelet Rich Fibrin (PA-PRF) system can guarantee a nearly 100% success rate of extraction and maintain an injectable liquid state for an extended period, allowing clinical doctors to use needles as fine as 34G, which is the thinnest needle, for treatment without preoperative anesthesia, minimizing the damage to human tissue and blood vessels during the surgical process. It is precisely because of these groundbreaking technological discoveries that experts can expand this technology to more unknown treatment fields for research and study.

In summary, the physical anticoagulation platelet-rich fibrin (PRF) technique has the following advantages:

Derived from autologous sources: PRF is prepared from the patient's own blood without the addition of potentially harmful additives (unlike traditional PRP, which requires anticoagulants and thrombin). This theoretically eliminates the risk of allergic reactions, infections, and rejection caused by non-autologous additives triggering the body's immune system, ensuring greater safety.

More effective components: Because no additives are used, the fibrin and growth factors in the blood are well-preserved during the extraction process, ensuring a low red blood cell count (compared to other non-patented extraction techniques).

Convenient operation: After collecting the blood, the PRF can be prepared with a one-button centrifuge within three minutes, ensuring stability of the extracted components.

Sufficient surgical time: The patented pure physical anticoagulation preparation technology ensures that up to 30 minutes of surgical time can be provided.

Low surgical risk: In addition to the improved safety mentioned in point 1, the physical anticoagulation PRF technique combines the advantages of traditional PRP and I-PRF. It can maintain liquidity for a longer period of time (>30 minutes) and supports the use of the finest 34-gauge needles for surgical treatment, minimizing the risk of damage to human tissues and blood vessels caused by medical devices and eliminating the use of anesthesia.

Long-lasting effects: PRF prepared by the UCHON patented physical anticoagulation device contains fibrin and various growth factors without adding any anticoagulants (during blood collection) or clotting agents (during injection), which can accurately target and promote repair. The natural coagulation reaction in the body activates repair signals, and the effect can last for 5 to 10 days, continuously promoting repair with more significant therapeutic effects than traditional PRP.

Broad prospects for development: Various plasma preparation techniques from autologous blood and their application in different medical scenarios have been globally recognized. However, traditional PRP and I-PRF techniques still have certain limitations, with relatively few indications beyond sports injuries, joint maintenance, and medical aesthetics. Physical anticoagulation PRF technology breaks through the limitations of traditional techniques and provides more research and clinical practice space for scientific and medical experts. More indications are waiting to be explored, and every new indication discovered will be a breakthrough in treatment options.

Overall, the physical anticoagulation PRF treatment technique has controllable costs in all aspects, from equipment to surgery. The various advantages based on our patented technology make us look forward to working with scientific and medical experts and institutions worldwide to provide a more cost-effective and better choice for overcoming disease and pain to the global population. We earnestly hope that more people with the same vision will join us in benefiting the public with this technology.

Comparative research of PA-PRF, PRP, PFR and I-PRF

The use of different blood-derived products to stimulate the healing and regeneration of soft tissues started more than 40 years ago. At present, the main medical techniques apply to Cosmetic Surgery, Hair Rejuvenation, Pain Management and Dentistry in China are PRP (Platelet-rich plasma), CGF (Concentrate Growth Factors), PRF (Platelet-rich Fibrin) and PA-PRF (Physical Anticoagulant-Platelet Rich Fibrin). PRP is the most common technique on the market due to it can be used for a range of conditions, yet anticoagulants and activators added during PRP operation make it a certain risk. PA-PRF is extracted from whole blood too but it’s autologous with no additives during the operation, which invented by Dr. Yuezhong Zhai in 2015. The following comparison table is showing the difference between PA-PRF & PRP in many aspects.

PRP vs. PA-PRF

PRP has been questioned internationally 22 years ago, owing to the anticoagulant can weaken the effect of the active ingredients in the body, and the activators can causeallergies, it may even cause irreversible coagulation disorder, it’s all the additional anticoagulants and activators to blame. In 2014, Dr. Choukron invented the I-PRF (injectable platelet-rich fibrin) which is an organic compound extracted from the whole blood processed by centrifugation, the use of additions like anticoagulant or activator is not required in the operation of I-PRF, it lows the risk and now widely adopted in Western developed countries, though it can’t leave much time for doctors to operate. Dr. Yuezhong Zhai upgraded the preparation of PRP to PA-PRF which additions are not necessary and offers more than 30 minutes procedure time due to its temperature being controlled under the coagulation point, Dr. Yuezhong Zhai designed a set of equipment and market launched in 2015, PA-PRF now is gradually accepted by hospitals and doctors in China, It not only solves the problem that PRP needs to use anticoagulants and activators that have certain risk, but also solves the problem that I-PRF can’t allow the doctors enough time to complete the procedure unhurriedly and cannot be injected with very fine needles, which is that PA-PRF can meet various clinical needs.

PA-PRF vs. PFR vs. I-PRF