Bone Grafting using Platelet Rich Fibrin (PRF)

Biological Bone Grafting Materials for Implants

The bone grafting materials that Dr. Yuriy May employs in the Natural Dentistry practice have been hand-selected through extensive clinical research and are, by design, considered the most effective and with the least amount of side effects.  Dental grafting material choices that are the most natural for the body are usually a mix of Platelet Rich Fibrin “PRF” and bone from the patient, referred to as “autologous” grafting. Autologous bone also known as “sticky bone” and PRF have infection-reducing properties, along with helping blood clotting in a bone graft, thus allowing the bone graft material to hold together and form healthy bone with improved density over other potential grafting options. Few conventional dentists or oral maxillofacial dental surgeons use materials that are limited to autologous grafting choices as they are harder to harvest and require spinning patients’ blood or retrieving patients’ own bone scrapings from surgical sites.

Dr. May’s choice of materials requires more time, effort and cost on the part of the dentist relative to the more conventional and widely used animal or synthetic bone graft material made of either animal material (bovine or porcine) or synthetic compounds, including various forms of PTCP (beta-tricalcium phosphate). Dr. May is an early adopter and key dentist in the country using autologous Platelet Rich Fibrin Therapy (PRF), working with leading researchers like Dr. Rick Miron to help provide real-time clinical feedback from healing sites and surgical results which has helped shape the field of PRF research in dentistry and medicine. Dr. May is an expert at creating and using all forms or PRF Therapy: i-PRF, A-PRF, L-PRF and horizontal PRF.

PRF is Dr. May’s primary bone graft material for maxillofacial surgery, bone growth and bone regeneration and is used in some of the following ways:

• Guided bone regeneration (GBR)
• Guided tissue regeneration (GTR)
• Bone Defects
• Extraction Sockets
• Sinus Lift & Sinus Perforation
• Jaw Ridge Augmentation & Grafting (Ridge Split)
• Palatal Defects
• Maxillary bone atrophy
• Mandibular bone atrophy

Platelet Rich Fibrin (PRF) Bone Grafting

Dr. May’s grafting material, PRF, is extremely effective, beneficial and safe because it is made from patients’ very own blood thus making it 100% natural, derived from patients’ own bodily tissue. PRF is 100% autogenous (meaning it comes from the patients’ own body) and is derived 100% from the patient’s blood.

In a simplified chairside procedure, the blood is taken from the patient virtually painlessly into several tubes, then spun down into serum with white blood cells and healing properties and used as the perfect grafting matrix instigating dense, healthy, and incredibly robust bone growth, which is the goal of a bone or any tissue graft. The centrifuge procedure results in the production of a thin, compressed layer of Fibrin that is strong, pliable and suitable for suturing. This natural fibrin network is rich in platelets, growth factors, cytokines that are all derived from the blood platelets and leukocytes.⁽¹⁾ The presence of these proteins has been reported to produce rapid healing, especially during the first seven (7) days after placement. ⁽²⁾ This network promotes more efficient cell migration and proliferation without chemical or bovine thrombin additives⁽³⁾

The materials described below have been very well studied and documented for many years. Dr. May’s patients experiencing the largest bone grafts in the case of sinus lifts and large ischemic bone disease grafts typically only need a mild pain reducer such as ibuprofen or acetaminophen afterwards if they have had a dental bone graft with any of the below materials. Dr. Yuriy may has an extremely high success rate in rebuilding and transplanting bone for dental implants and for full mouth reconstruction cases, including post-dental cavitation / IBD procedures.

Platelet Rich Fibrin (PRF)

Platelet Rich Fibrin has exploded in its adoption and usage in the last 5 years with the help of researchers like Dr. Rick Miron and Dr. Choukroun, and incredible clinicians like Dr. Yuriy May who were early adopters of this most novel and effective bone regeneration and bone grafting technique. PRF is 100% autogenous (meaning it comes form the patients’ own body) and is derived 100% from the patient’s blood. Outside of PRF, no other grafting material can govern and stimulate all 3 of the key processes involved in tissue and bone regeneration including angiogenesis, chemotaxis and cell proliferation. To this date, no exogenic agent can effectively govern all these processes, clearly highlighting PRF’s superior properties relative to traditional synthetic and allograft grafting materials.

It is estimated that less than 15% of dentists the USA use PRF for grafting and most instead choose to use allograft, xenograft or other non-autologous bone grafting materials. Dr. Yuriy May is one of the few dental implant specialists using predominantly autologous bone grafting and platelet-rich fibrin as the only ingredients for bone grafting for dental implant placement.

Why is Platelet Rich Therapy the Optimal in Bone Grafting & Tissue Regeneration?

Platelet rich therapy is the ultimate bioavailable therapy for stimulation and regeneration of cells in the body. While various growth factors are routinely used in reconstructive and regenerative therapies, the platelet rich fibrin therapy is the simplest and one of the most effective methods to extract growth factors from the blood’s platelets.

The Process of Platelet Rich Therapy and Blood work

Spinning to create PRP, PRF, i-PRF, A-PRF and L-PRF
In the office, Dr. May takes a blood draw from a patient and inserts the blood into a centrifuge to start the PRF procedures. The entire process takes approximately 20-30 minutes. Both PRP (platelet rich plasma), and PRF (platelet rich fibrin) can be extracted from the blood cells using the centrifuge. After the initial blood draw from the patient, a platelet concentrate technique is applied through use of the centrifuge to separate the blood’s components, with the goal of increasing and concentrating the platelet count. The most essential component is the clotting because the platelets release their growth factors only after clotting, and it is after the growth factors are created that their use can be determined.

PRF
In PRF, the white cells are in the bottom of the clot. If blood is spun a high G force, valuable cells can be destroyed and to preserve the cells, Dr. May spins the blood cells using a reduced RPM (revolutions per minute) and lower G force, to maximize the cell count and usage of the blood cells.

iPRF: Injectable-PRF (i-PRF) is the injectable version of PRF, which is liquid. i-PRF is made slightly differently, with an even lower G force, of 60 only (vs 200 for A-PRF) — followed by the same protocol, with no additive and no anticoagulant. The goal of i-PRF is to create a formation of a high concentration of white cells, plus fibrinogen, plasma protein have it clots spontaneously after the injection. Nothing additional needs to be added into the injection site to get the clot and to get the platelet to release growth factors. Injectable-PRF can be created by spinning for only three minutes. Spinning for four minutes will reduce the quality while increasing the liquid content and is generally suboptimal. The best concentration of the stem cells is spinning only for three minutes. More blood can be used to create more liquid.

A-PRF: Advanced PRF (A-PRF) forms a clot, creating a thicker, gel-like substance. With the A-PRF, the RCF (relative centrifugal force) is low: 200 G force — in order to get more white cells. An eight minute spin is needed to create A-PRF. Increasing the white cells, increases both vascularization and release of growth factors. By increasing vascularization, the vessel density and the percentage of vascularization can also be increased.

L-PRF: Leukocyte-Platelet Rich Fibrin is a mucous-like membrane formatted out of PRF and is rich in leukocytes, with higher volume of white cells than both i-PRF and A-PRF. In a study conducted with 26 patients and over 108 extractions among all the patients, outcome of the L-PRF extraction grafted sockets vs the non-grafted control sockets showed better healing and faster socket closure for the sockets treated with L-PRF, with differences statistically significant at days 3 and day 7.⁽⁴⁾ L-PRF tends to create the most properties among PRF membranes, which are effective in large scale grafting cases especially for periodontal therapy including superior tensile strength, stiffness, and toughness relative to PRGF Endoret.

Plasma Rich in Growth Factors (PRGF) / Platelet Derived Growth Factors (PDGF):
The purpose of PRGF is a higher concentration of human growth factors, derived from the platelets or thrombocytes. The growth factors ensure that the tissue regenerates itself after an injury or after surgery. The growth factors can be separated from the platelets or activate with the thrombocytes which are separated from the rest of the blood, and only brought to those locations where targeted growth and cell activation are to be stimulated. The highly effective and side effect free PRGF therapy was developed in 1999 under the name Endoret (R) Endogenous Regenerative Technology but the Spanish Research Group led by Dr. Eduardo Anitua. Overall, the wound healing period is shortened by the concentrated action of growth factors, and the risk of complication is significantly reduced. However, it is an open system in which calcium sulfate has to be added to produce the memberane, giving it its high tensile strength.

Difference in A-PRF and i-PRF
The main difference between Advanced PRF (A-PRF) and injectable PRF (i-PRF) is that A-PRF is a gel like substance used for bone and tissue grafting in the gingiva, while i-PRF is a liquid form used to regenerate tissue through injection.

Difference in Old School PRP and the Superior PRF
When comparing the white cells between PRP and i-PRF, i-PRF has over 20x (20 fold) more white blood cells also known as cytokines. However, the level of the platelets is the same in all three techniques (PRP, A-PRF, i-PRF); as the the difference in G force during centrifuging does not reduce the platelet enrichment.

How does the biology of Platelet Rich Therapy Work?

For PRP, the platelets are enriched 2x to 4x and few white cells remain.

For PRF, there is no anticoagulant added during the spin, the clotting is physiological and the spin creates a clot, which contains platelets, white cells and fibrin. In the PRF, there are all platelets, 50% of white cells and all the fibrin of the blood. The role of the fibrin is very specific, it’s a recipient of growth factors and this recipient will allow very specific release of growth factors, very slowly and continuously over a time period of more than one week. PRF can be prepared as aPRF (gel form) for gum grafting and bone grafting or iPRF (liquid form) for tissue shaping and stimulating collagen around the mouth and smile lines.

Natural Dentistry uses growth factors to not just for tissue stimulation for tissues undergoing regeneration, but to regenerate hard tissue – to regenerate and grow bone. While bone stimulation itself only needs the platelets, with or without leukocytes, the ultimate goal of regeneration requires fibrin. Regeneration requires a scaffold, which is created upon Dr. May adding in the fibrin matrix, in addition to platelets and leukocytes. The most critical element for the biological interaction of PRF to work optimally is the amount of growth factor released into the grafted site and not the concentration of growth factor in the actual substance, which needs to be released in a stable manner over the course of weeks for bone and/or soft tissue to regenerate.

To regenerate tissue we need a scaffold that the body can not provide without Dr. May’s manipulation of a patients blood, as fat is insufficient on its own to create a matrix. While fat can be used as a base, the most efficient scaffold in the body is fibrin.

How is PRF used outside of dentistry in medicine, dermatology, and cosmetic facial aesthetics?

By using PRF as a matrix, it can be used to promote healing in an infected wound. Examples include post-surgery infection and necrosis, for example in a diabetic foot, after amputation. The concept is to inject the fibrin with growth factor, and the fibrin will release over a few days. “By leaving the wound untouched for four to five days, a very fast vascularisation can be achieved without any anti-infectious threat. If vascularisation can be achieved on the surface, the healing is very easy, because the vessels are doing the job by slowly infusing the growth factors.”⁽¹⁰⁾

The healing in soft tissues always begins with formation of a provisional matrix. While all PRF components are active, the tissue needs platelets and the white cells most in the beginning. The objective is to create homeostasis and inflammation, to draw blood and vascularization to the area of treatment. After five – seven days granulation tissue begins to form and the matrix deposition becomes visible because the endothelial cells and the fibroblasts start to work, and after ten days collagen forms within the treated tissue. The provisional matrix is the most important, because when fibrin is introduced to into the site new vascularisation is immediately created.

Cell biology and the creation of collagen

Both plasma protein and white cells are necessary to create collagen synthesis, as white cells stimulate the inflammation response needed to draw fresh blood flow to the treatment area to create vascularization. At an injury site, the endothelial cells immediately separate themselves and then the white cells squeeze through the gaps and then by chemotaxis they move through the injury site, and begin to release the pro-inflammatory interleukins. This is the sort of inflammation that causes activation of monocytes into macrophages. The macrophages then dominate the inflammatory phase, and then they start to release growth factors and BNPS. Stem cells are necessary alongside white cells in order to achieve a smart blood concentrate and regenerate new tissue. White cells influence the quality of the PRP, so enriching the PRP with white cells creates greater tissue augmentation and a significantly higher proliferation of mesenchymal stem cells.(10)

Platelet Rich Plasma (PRP) – The Original “100% Natural Autogenous Grafting Material“

PRP, or platelet-rich plasma therapy is (not to be confused with newer, superior PRF or platelet rich-fibrin therapy) was used earlier in dentistry to accelerate bone and tissue growth and wound healing and help assure long-term success of dental implant placements. PRP was the premium grafting material for sinus lift bone grafts, onlay block bone grafts, bone and ridge expansion, extractions, nerve repositioning and most surgical dental procedures approximately 5-7 years ago. In addition to PRP’s amazing properties for accelerated healing of dental implant procedures and excellent bone growth regeneration, the all natural and highly effective bone grafting medium was quickly gaining acceptance in orthopedics and sports medicine as well. Various orthopedic physicians have been using PRP with success for painful and hard to treat injuries like tennis elbow, tendonitis and ligament damage. It is worth mentioning that PRP was used in 2009 pre-game Super Bowl treatment for two Pittsburgh Steelers players (Heinz Ward and Troy Polamalo), and both were instrumental in the team winning its 6th Super Bowl. James Rutkowski, DMD, PhD, and a prominent dental researcher and editor of the Journal of Oral Implantology reported at the recent annual scientific meeting of the American Academy of Implant Dentistry (AAID) that platelet-rich plasma therapy can accelerate bone and tissue growth and wound healing and help assure long-term success of dental implant placements.

In the last 5-7 years a new, a more superior form of PRP was discovered which is now known as PRF – Platelet Rich Fibrin, which is 10x the regenerative power and growth factors of PRP. The most prolific and progressive dentists and doctors all over the world, like Dr. Yuriy May, have long moved on to PRF instead of the outdated and inferior PRP.

“What could be better than using the body’s own regenerative powers to grow bone and soft tissue safely and quickly? For dental implant procedures, PRP treatments can jump start bone growth and implant adherence in just two weeks, which cuts down the time between implant placement and affixing the dental crown,” said Dr. Rutkowski.

Platelet-rich plasma is obtained from a small sample of the patient’s own blood. It is centrifuged to separate platelet growth factors from red blood cells. The concentration of platelets triggers intense, rapid growth of new bone and soft tissue.

“There is very little risk because we are accelerating the natural process in which the body heals itself,” says Dr. Rutkowski. “PRF speeds up the healing process at the cellular level, and there is virtually no risk for allergic reaction or rejection because we use the patient’s own blood.”

For dental surgery applications PRF is mixed as a gel that can be applied directly in tooth sockets and other sites within the oral cavity. It highly effective in cases when bone grafts are required to foster proper bone integration for dental implants, which is where Dr. May exclusively uses PRP. Growth factors in PRP preparations help the grafts bond faster with the patient’s own bone. Studies by Dr. Rutkowski have reported findings of increased radiographic bone density during the initial two weeks following PRP treatment when compared to dental implant sites that did not receive PRF treatment.

“Accelerated healing is a goal we’re constantly seeking in implant dentistry and we now have treatment that activates the natural healing process. It is a most promising development for implant dentistry,” explained Dr. Rutkowski.

Currently, only 10% of practicing implant dentists use PRP treatment due the higher level of effort and expertise required by the dental implant specialist, however, PRP is widely considered as setting the bar for best in class bone grafting material in the holistic and implant dentistry field.

Other Bone Grafting Materials

Traditional Non-Autologous Bone Grafting Materials

There are currently procedures to save or preserve bone, and there are a number of conventional bone graft materials available to be used with these procedures in dentistry today, all of which are suboptimal in holistic dentistry as they use foreign material to create a matrix to rebuild a dental patients’ oral and facial bone structure.

They include:

Autograft: Recipient’s Own Bone
Autograft is obtaining of bone from the patient’s own body and typically is the gold standard grafting procedure available now.
Concerns: Autograft has its limitations, which include potential problems such as second surgical site and patient discomfort in terms of harvesting of a graft from another part of the patients body. It’s also a painful, complex and costly procedure for the patient.

Allograft: Bone from another Human Being
Allograft is obtaining of bone graft materials from human cadavers.
Concerns: The disadvantage of allograft is that the bone graft materials may be rejected by the recipient’s immune system. Also there is chance of disease cross transmission.

Xenograft: Bone from animal, usually porcine or bovine origins
Xenograft is the obtaining of bone graft materials from tissue of animal origin, which includes bovine (cow’s bone) or porcine (pig’s bone)
Concerns: Similar to allograft, such bone graft materials may be rejected by the recipient’s immune system or pose concerns of potential disease transmission.

Alloplast: Synthetic grafting materials
Alloplast are synthetic grafting materials used for grafting.
Concerns: They have limitations in terms of biocompatibility, resorption timing, local tissue reaction, and bone regeneration.

Non-Autologous Biological Grafting Materials

Recombinant Human Bone Morphogenic Protein (rhBMP-2)

This is an additive known as recombinant human Bone Morphogenetic Protein-2 (rhBMP 2) made by Mectron.BMP is something that helps bone grow. BMP increases the price of dental implant bone grafts by $1,500 to $5,500, only for the BMP additive itself, not including the actual bone graft or dental implant and abutment or the restorative crown! But, interestingly, BMP is not something Dr. May considers necessary in all cases because it is possible to extract the natural Bone Morphogenetic Protein that each individual makes through the PRF (platelet-rich plasma therapy). Unlike PRP or PRF, the BMP available on the dental market is derived from other human beings instead of the 100% bio-identical PRF made from each patient’s very own plasma and blood.

Clinical Research & Studies

In recent research,  the objective was to try to extract stem cells from the blood. A flow cytometry was conducted to analyze the mesenchymal stem cells into the iPRF. Using information from the International Society for Cell Therapy, it was known researchers needed to find cells that are CD 34- and 45-, and CD44+, CD73+, CD90+ and CD105+ positive, since those are the characteristics of the mesenchymal stem cells. The scientists performed an elimination of all the cells, and found that in the iPRF they have a 1% to 3% of mesenchymal stem cell concentration – far outpacing current PRP stem cell concentrations. When researchers analyzed the iPRF they found the magical cells they’ve been looking for: a concentrated quantity of if stem cells that equaled 1%-3% of total Platelet Rich Fibrin cells.
At Natural Dentistry Center, it is possible to produce thousands of stem cells in just three minutes, by collecting patients’ blood into several small 100 ml tubes and spinning in a centrifuge with a low force. When comparing the concentration of the mesenchymal stem cells in the new iPRF to the older and more known PRP, the difference of concentrated stem cells and growth factors using a low spin speed in the centrifuge is evident. Dr. May only needs to draw a patient’s blood, spin it in the centrifuge for three minutes at 900 rpm in the iPRF tube, without any additive, without any anticoagulant. It’s that simple.

Summary of some Research Exemplifying the Power and Depth of Research of Platelet Rich Fibrin in Dentistry:

Regenerative Medicine: PRF Part 1

“The PACT (Platelet & Advanced Cell Therapies) Forum: fostering translational research, transdisciplinarity and international collaboration in tissue engineering and regenerative medicine”

Gilberto Sammartino, Marco Del Corso, Lidia M. Wisniewska, Tomasz Bielecki, Isabel Andia, Nelson R. Pinto, Chang-Qing Zhang, De-Rong Zou, and David M. Dohan Ehrenfest. POSEIDO, Volume 2, Issue 2, June 2014, Pages 105-115

Abstract: The PACT (Platelet & Advanced Cell therapies) Forum Civitatis of the POSEIDO was created to offer a multidisciplinary platform of research, publication, debates and eventually consensus for researchers in the fields of Tissue Engineering and Regenerative Medicine (TERM). In this review, the issues, endeavors and perspectives of this considerable research field are discussed and illustrated, particularly (but not only) through the example of the history, failures and success of probably the oldest method developed in regenerative medicine, the topical use of autologous platelet concentrates (commonly known as Platelet- Rich Plasma – PRP or Platelet-Rich Fibrin – PRF). The History of this domain illustrates very well that the greatest enemy of knowledge is not ignorance; it is an illusion of knowledge. Fighting against illusions in Sciences is a very complex and tricky task, requiring continuing efforts and time. This PACT for a transdisciplinary, translational and international approach in regenerative medicine is an important step in this endeavor.

Keywords: Blood platelet, fibrin, growth factors, regenerative medicine, tissue engineering.

Regenerative Medicine: PRF Part 2

“The impact of the centrifuge characteristics and centrifugation protocols on the cells, growth factors and fibrin architecture of a Leukocyte- and Platelet-Rich Fibrin (L-PRF) clot and membrane. Part 1: evaluation of the vibration shocks of 4 models of table centrifuges for L-PRF.”

David M. Dohan Ehrenfest, Byung-Soo Kang, Marco Del Corso, Mauricio Nally, Marc Quirynen, Hom-Lay Wang, and Nelson R. Pinto. POSEIDO, Volume 2, Issue 2, June 2014, Pages 129-39.

Abstract: Each centrifuge, profile of vibrations, RPMs of rotational speed and time may significantly impact the characteristics of PRF, a surgical adjuvant used to improve healing and promote tissue regeneration in maxillofacial regenerative therapies in dentistry.

Background and Objectives: Platelet concentrates for surgical use (Platelet-Rich Plasma PRP or Platelet-rich fibrin PRF) are surgical adjuvants to improve healing and promote tissue regeneration. L-PRF (Leukocyte- and Platelet-Rich Fibrin) is one of the 4 families of platelet concentrates for surgical use and is widely used in oral and maxillofacial regenerative therapies. The objective of this first article was to evaluate the mechanical vibrations appearing during centrifugation in 4 models of commercially available table centrifuges frequently used to produce L-PRF.

Results: Very significant differences in the level of vibrations at each rotational speed were observed between the 4 tested machines. .

Discussion and Conclusion: Each centrifuge has its clear own profile of vibrations depending on the rotational speed, and this may impact significantly the characteristics of the PRP or PRF produced with these devices.

Regenerative Medicine: PRF Part 3

“Immediate implantation and peri-implant Natural Bone Regeneration (NBR) in the severely resorbed posterior mandible using Leukocyte- and Platelet-Rich Fibrin (L-PRF): a 4-year follow-up”

Marco Del Corso and David M. Dohan Ehrenfest POSEIDO. 2013;1(2):109-16 Natural Bone Regeneration (NBR) with L-PRF

Abstract: In the severely resorbed posterior mandible, the placement of dental implants in ideal position is often compromised by the significant post-extraction centrifuge alveolar bone resorption. The shape of the residual alveolar ridges and the residual bone height above the inferior alveolar nerve often make the area not suitable for direct implantation. Even if the use of short implants offers excellent results when the residual bone volumes are high and wide enough to receive these implants [1], there is no other solution than bone regeneration surgery prior to implant placement when the alveolar ridges are very thin [2]. However bone regeneration itself remains a challenge in this area, as the mandibular posterior residual alveolar ridges are always very cortical with a low vascularization and therefore not really adapted to the integration of bone grafting material or regeneration of bone cavities. Finally, the posterior mandible is a place of significant mechanical constraints applied on the bone and gingival tissues during the mastication function, and this can compromise the healing of a bone regeneration chamber, particularly through the risk of soft tissue dehiscence after the regeneration surgery.

Regenerative Medicine: PRF Part 4

Other Applications of i-PRF

Several dermatologists and osteopaths have treated patients with arthritis in the knee and hip, with the discovery that iPRF has the capability to regenerate cartilage and reduce pain. Several of Dr. May’s physician partners, including Dr. Paul Tortland of Valley Sports Physicians in Avon Connecticut, have improved pain relief by injecting iPRF into arthritic joints. Multiple studies and patient testomonials have documented the results of iPRF Therapy, including regeneration of the cartilage with the stem cells from the iPRF, reduced inflammation, and reduced pain. Applying iPRF to the scalp with microneedling can improve the hair growth when the patient has alopecia or undergoes hair restorative procedures. iPRF may also be used in the lips to regenerate collagen and improve fullness, plumpness and overall appearance.

References:

1. Dohan Ehrenfest DM, Del Corso M. Diss A., et al. Three Dimensional Architecture and cell composition of a Choukroun’s platelet-rich fibrin clot and membrane. J Periodontal. 2010 Apr;81(4)546:55.
2. Dohan Ehrenfest, David M.; de Peppo, Guiseppe; Doglioli Pierre; Sammartino Gilberto. Slow Release of Growth factors and thrombospondin-1 ub Choukroun’s platelet-rich fibrin (PRF); a gold standard to achieve for all surgical platelet concentrates technologies. Growth Factors. Volume 27, Number 1, February 2009, pp.64-69(7)
3. Dohan DM., Diss A, Dohan SL, Dohan AJ, et al. Platelet-rich fibrin (PRF); a second generation platelet concentrate. Part III: leucocyte activation: a new feature for platelet concentrates? Oral Surg Oral Med Oral Pathol Oral Radiol Endo. 2006 Mar;101(3):e51-5.
4. Marenzi G, Riccitiello F, Tia M, di Lauro A, Sammartino G. Influence of Leukocyte- and Platelet-Rich Fibrin (L-PRF) in the Healing of Simple Postextraction Sockets: A Split-Mouth Study. BioMed Research International. 2015;2015:369273. doi:10.1155/2015/369273.
10. “Stimulation and regeneration” by Dr. Joseph Choukroun, 3/31/2016
11. HA injections paired with iPRF increase collagen formation and reduce the amount of Hydrolauronic Acid needed to be used due to iPRF’s property of generating far more collagen and acting as the perfect cellular framework to generate HA stability