RICHARD J. MIRON, DDS, MSC, PHD, is the lead educator and researcher at Advanced PRF Education and an adjunct visiting faculty member in the Department of Periodontology at Bern University in Bern, Switzerland. He has published more than 350 peer-reviewed articles and 8 textbooks, and he lectures internationally on many topics relating to growth factors, bone biomaterials, and guided bone regeneration.
Inside Dentistry (ID): How important is gingival tissue health and healing to the long-term success of an implant case?
Richard J. Miron, DDS, MSc, PhD (RJM): Generally speaking, it's extremely important to have proper soft-tissue integration to a dental implant to support faster soft-tissue attachment. The faster you can get proper attachment, the faster you can essentially prevent bacteria from the oral cavity from entering/attaching to the bony levels of the implant (ie, roughened surfaces). This was one of the main reasons why BioHorizons initially spent a lot of time in research developing Laser-Lok® surfaces. They realized early on that faster soft-tissue attachment to the coronal portion of their implants could lead to better long-term maintenance. In addition, biologic agents capable of speeding soft-tissue wound healing are also excellent options for tissue healing around implants. In particular, platelet-rich fibrin (PRF) has been shown to improve soft-tissue healing around both implants and teeth. Many years of research have been conducted, and many techniques have been developed to help clinicians optimize their outcomes in implant dentistry using PRF.
ID: When it comes to grafting, what are some of the most common mistakes or oversights that you see clinicians make?
(RJM): I would say that the most common oversight in clinical practice is in fully understanding the biologic features of biomaterials. We've spent a lot of time and energy to really understand the differences between the various classes of bone grafting materials, the different membrane types, and what each growth factor does. In 2019, I realized along with one of my colleagues, Yufeng Zhang, MD, DDS, PhD, that many clinicians had a very limited knowledge of biomaterials. Our laboratory had basically focused on this for 20 years, so we published a summary textbook on everything that we had studied over the past 2 decades titled, Next Generation Biomaterials for Bone & Periodontal Regeneration. It highlights the importance of truly understanding biomaterials. I would say that before getting started with any surgical techniques, such as how to perform guided bone regeneration, sinus grafting, implant placement etc, a clinician should also dedicate some time to completely understanding the biologic properties of the available biomaterials at their disposal.
ID: What role does PRF play in optimizing wound healing, and how has its use evolved in your practice?
(RJM): Over the years, we've learned that the body has an amazing intrinsic ability to heal itself. I always say to clinicians, or even to patients, that if you're in the kitchen cutting cucumbers and cut yourself, it's pretty amazing to think that your body is going to heal all by itself. How does that happen? Circulating blood has different types of growth factors and cells, and when these circulating proteins (eg, fibrinogen, thrombin) are exposed to air and oxygen, a clot will form. Once the clot forms, cells and growth factors get trapped in the clot, and then over the next 21 days or so, you're going to heal all by yourself. Your body is literally sending every cell in the right order, orchestrated by many signaling molecules, growth factors, and cytokines, all playing important roles in the healing process. The body naturally does this all by itself, which is quite amazing.
Based on these intrinsic abilities to heal, Robert Marx, DDS, a professor of oral and maxillofacial surgery at the University of Miami, questioned whether we could utilize this innate healing potential and super-concentrate these important growth factors and cells. He asked, "Could we literally draw blood, super-concentrate the growth factors in a centrifuge, and then use this new formulation in regenerative medicine and dentistry?" He then coined the term platelet-rich plasma (PRP), and many studies in medicine and dentistry have since been performed. As the years have progressed, research has demonstrated the exact clinical indications for which PRP and PRF show positive benefits. Furthermore, we have identified when we can use the technology alone versus when we should combine PRF with other biomaterials.
In a nutshell, studies have now indicated that PRF is much better for soft-tissue healing than bone healing. However, in the bone field, we know that PRF improves the vascularization of tissues. We also know that we can create a "sticky bone" matrix, which is PRF mixed with bone graft particles, to improve the handling of graft particles in clinical practice.
When it comes to how the use of PRF has evolved in our practice, we've done a lot of work in our research laboratory to determine the best way to optimize its production and superior ways to concentrate cells in the PRF matrix. Now, we only utilize horizontal centrifugation versus fixed-angle, understand the protocols much better, and utilize chemical-free tubes (many centrifuge tubes still have chemical additives inside). I would say that the most remarkable evolution in the practice has been the improvement in our understanding of how to produce the best quality PRF for our patients.
ID: Is there anything that clinicians commonly fail to understand about PRF?
(RJM): Many fail to understand that success is directly related to their understanding of the technology. It's about understanding the protocols, understanding the difference between G-force and RPM, and the number one issue that I see that leads to making mistakes-understanding the importance of using proper PRF tubes. It's interesting because you can buy a PRF centrifuge anywhere from $1,000 to more than $10,000, but that decision doesn't matter nearly as much as the decision you make regarding what tubes you buy. A lot of clinicians are using hospital tubes or tubes that are meant for different purposes. Many of those tubes actually have chemicals inside them. For example, some of them are laced with silica or silicone along their inner walls, and following the centrifugation cycle, these chemicals will end up in your PRF and, subsequently, into your patient at the site of surgery, potentially causing unnecessary additional inflammation. So, while these clinicians are trying to do something really positive for their patients by using PRF in their surgeries, they may actually be doing more harm by preparing PRF inappropriately.
ID: How does healing at a grafted implant site impact the risks of peri-implant disease?
(RJM): The incidence of peri-implantitis is growing year after year, and of course, for specialists that are in certain cities and areas, we're seeing more and more of these cases. It's becoming a disaster, quite honestly. Personally, I believe that the risk of peri-implantitis is exponentially increased in immediate implant dentistry. And the reason why is that when we place immediate implants, oftentimes, there are quite significantly sized open gaps where bacteria can infiltrate the area. Let's say, for example, that we're placing an implant in a lower first molar site. There will naturally be 1 to 2 mm of open space between the implant and the bony walls. Of course, we'll graft the area, typically with a bone allograft; we'll place a healing abutment, either a stock abutment or a custom healing abutment; and we'll try to proximate the tissues as best we can against the abutment. However, what I think clinicians are failing to comprehend is that bacteria are approximately 5 microns in size, which is extremely small, and they want to and do become invasive, which I'll further explain.
The opportunity for bacteria to squeeze in between the soft tissue and the healing abutment and go straight downwards toward the implant is very likely. And, as I tell clinicians that take our PRF courses, when this happens, those bacteria are very happy to colonize on the roughened portion of the implant surface and propagate. They colonize, they proliferate, and the implant is on its way to developing peri-implantitis. I always tell clinicians that "the day that you place a dental implant is the most important day of that implant's life, and this is further magnified when placing immediate implants."
A technique for using PRF in implant dentistry that is referred to as the "poncho technique" was developed whereby a small incision is made in a PRF membrane, through which the healing abutment is passed. In a nutshell, the space between the soft tissue and the healing abutment is filled with PRF. In randomized clinical trials, this technique has been shown to facilitate faster soft-tissue healing to the abutments at the coronal portion of the implant and also to prevent bacteria from entering and making their way downward to the roughened portion of the implant's surface. I would say that appropriately managing soft tissues via the use of PRF, especially during immediate implant placement, is going to be a pivotal and vital step in attempts to minimize peri-implantitis in the future.
ID: What is the most important thing for clinicians who are interested in incorporating PRF into their implant surgical procedures?
(RJM): The most important thing is that they acquire the appropriate knowledge/education to fully understand the protocols. I've done a lot of laboratory research with Professor Masako Fujioka-Kobayashi, DDS, PhD and Yufeng Zhang, MD, DDS, PhD, to really optimize platelet concentrates. When we used to teach PRF courses in Switzerland, Masako would always tell doctors, if you are going to go through all of the trouble of literally taking a needle, sticking your patient, and drawing 4 to 6 tubes of blood from his or her arm, etc, then you'd better know exactly how to spin the blood with the correct centrifugation protocols to optimize the PRF. In addition, you need to know exactly from which layers you should be drawing up the PRF or making membranes from. If you don't fully understand the science, then you won't fully achieve the desired results. Too often, we find that doctors will just go to eBay or Amazon, buy a centrifuge and hospital tubes, and then start drawing blood and spinning it in whatever way they want to spin it. Maybe they learned these protocols from Instagram or Facebook as opposed to peer-reviewed scientific publications. So, if you're new to PRF, I would say that the most important thing is to get properly educated, ideally before even starting. We have many publications that are available and free to download. Studies have shown you can end up harvesting about four times less cells and growth factors in the final PRF product with incorrect protocols. That could be decreasing the regenerative potential by up to 400%, and it's the biggest mistake that I see being made by clinicians who are new to PRF.
ID: From a clinical standpoint, what are the most critical steps to take preoperatively to maximize success with PRF in implant surgery?
(RJM): From a clinical standpoint, I would say that the most important thing is to ensure that your team is very well trained. One thing that I've seen over the last 10 years of following our PRF courses is that dentists are very busy. Their clinical time is very valuable. If dentists have to go into a room, do the blood draw themselves, take the blood and spin it themselves, process the PRF themselves, and then make the sticky bone themselves, that's going to add a lot of extra surgical time to procedures. We see such clinics drop off quickly from doing PRF. Instead, assistants with proper phlebotomy licensure should be used to draw the blood, spin it down, and perform any of these steps that would otherwise be done by the dentist. This saves the dentist a lot of valuable chair side time, and many assistants enjoy performing these steps. It makes them feel that they are an important part of the team. In my experience, practices that are doing PRF with highly skilled team members are a lot more successful. The team should be preparing everything step-by-step, and the doctor just walks into the room and has everything PRF-related ready for use.
ID: How do you decide if a case will benefit from the use of PRF?
(RJM): As a clinical researcher and scientist, I would say that the answer to that question is to read the literature regarding where it has been shown to lead to positive outcomes. There's been hundreds, if not thousands, of randomized clinical studies that have been performed on PRF, and from those randomized clinical studies, there's been systematic reviews with meta-analysis that have really highlighted precisely where there's benefit and where there isn't benefit. Typically, any time that we're doing large bone augmentations, we like to add PRF to help with the handling of the bone graft material and improve vascularization. Also, anywhere where an incision is made during surgery, we like to close with a PRF membrane underneath. We've also seen benefits with using it in gingival recession coverage procedures, and we've used it quite frequently in the treatment of intrabony/furcation defects (both surgically and nonsurgically following scaling and root planing), so it has benefits to treating periodontal disease as well. There are really a number of applications for PRF, and honestly, anytime that we are performing surgery is basically the answer to that question. The scientific literature dictates when it will be utilized alone or in combination with other biomaterials based on the indication. Generally speaking, all implant-related surgeries will benefit from using PRF, especially for soft-tissue
healing and mitigating postoperative pain.
ID: How do you explain PRF to patients, and what do they think about it once it's been explained?
(RJM): I always try to explain things as simply as possible. I love my cucumber example because people just get that. When a patient comes in, I tell them that the body is an amazing thing and that we have this amazing intrinsic ability to heal ourselves. If you look at every single step of the healing process-how many cells, pathways, growth factors and cytokines are involved in an exact precise order-the body is truly amazing. But then I tell patients that as the body ages, that ability to heal starts to deteriorate, and a lot of it is related to blood flow. They say that for every decade of life, your max heart rate goes down by 10 beats per minute, so if your max heart rate was 220 when you were in your 20s, by the time you're 60, 70, 80 years old, that may decrease to 150. The muscles of your heart are getting weaker with age as well, so you're not able to pump blood nearly as effectively. For these reasons, your wound healing ability begins to decrease as well.
Furthermore, if you have a disease that affects blood flow, and the classic example is diabetes, that's when things can deteriorate really quickly. So, another example that I give patients is, if a person with a normal metabolism plays tennis, they can get blisters on their feet and heal just fine. But for the diabetic person, they may not heal. Their blisters could develop into diabetic ulcers, and if an infection develops, they may require an amputation. All of that is related to blood flow because they can't effectively pump enough blood from their heart to the bottom of their feet, which is the area of the body that is furthest from the heart. This is typically why diabetics have issues healing at their extremities. Those are the hardest areas for the body to pump enough of the regenerative cells that are found in blood.
With respect to platelet concentrates, I explain to patients that there was a doctor by the name of Robert Marx who realized that diabetic healing issues were related to insufficient blood flow and that blood cells and regenerative cells could not get to the defects as efficiently in older diabetics. So, Professor Marx came up with the idea of drawing some tubes of blood from these patients, centrifuging those cells in order to super-concentrate the important wound healing growth factors and cells, and applying this formulation of PRP directly to their defects, or even injecting it around the periphery, to improve healing. Sure enough, these patients started to heal faster, and that was because he was bringing the cells, growth factors, and nutrients right to the defects themselves, which their bodies could not do on their own. Over the years, the anti-clotting factors were removed from PRP to form PRF. Since then, many uses for these technologies in regenerative medicine and dentistry have been developed.
ID: Where do you see the biggest opportunities for growth in the field of regenerative dentistry during the next 5 to 10 years?
(RJM): I would note two major opportunities for growth. The first is in the use of biologic agents. I'm writing an article right now regarding the use of enamel matrix derivative. Emdogain® has been on the market now for 3 decades. I think that the use of growth factors in general and being able to understand which small biomolecules can specifically improve regeneration outcomes is going to be very important for the future. Currently, there's a lot of work being done with exosomes, which are small extracellular vesicles that are very stable. The work of combining exosomes with PRF and other growth factors is probably the biggest opportunity for growth. We're not going to be able to improve bone allografts or xenografts that much further.
The second opportunity for growth, which I've noticed as a PRF educator, is the opportunity for dentists to use the PRF skill set they acquired in implant dentistry to apply very similar techniques in facial esthetics. Of course, the smile is so important for facial attractiveness, but nowadays, most states permit dentists to perform facial esthetic procedures, so we can offer combination therapies. For example, if we do a full-arch implant case, we can also treat the remainder of the face by microneedling with PRF and/or administering PRF bio-fillers via simple facial injections. This creates new and interesting opportunities for dentists because you can make someone look a lot younger with these technologies, and it's all natural and very safe.
Figures and Images
Richard J. Miron, DDS, MSc, PhD
