The Leukocyte Platelet Rich Fibrin Technique

New techniques in dental treatment are constantly being developed. Oral health professionals need to remain aware of these advances to promote the best possible patient outcomes.

Today, treatment modalities can assist with the stimulation of tissue formation after dental surgical procedures. The placement of Leukocyte Platelet Rich Fibrin (L-PRF), taken from the patient’s own tissue, provides enhanced healing following specific dental procedures. Acting as a biologic modifier, L-PRF mimics and prolongs the effects of typical physiologic wound healing. By releasing the cytokines and platelets necessary for healing over an extended period, healing begins more rapidly and is accomplished at a faster rate. This is especially important in dentistry because many procedures require multiple steps before completion, with each step building and relying on the success of the previous one. For instance, in order for an implant to be placed, a patient must have an adequate amount of bone present for the implant to be stable and successful. If a tooth has been extracted or gingival tissue/bone has been lost, the patient must endure subsequent procedures to prepare the site before a dental implant can be placed. It can take as long as 6 months to 1 year before the patient completes treatment.

The L-PRF technique was first described by Choukroun in France in 2001.¹ It is an inexpensive technique using the patient’s blood to create a leukocyte fibrin-rich substrate that can be placed in areas of the surgical site in conjunction with supplemental tissue to stimulate bone and soft tissue formation as a biological modifier.² The use of L-PRF can provide the patient with enhanced healing, possibly fewer appointments, and a faster end result. As the procedure poses minimal risk of infection and complications, it is a valuable approach that has a variety of applications.

BONE/TISSUE GRAFTS

There are many circumstances when a patient may require a bone/tissue graft or other treatment to induce new bone/tissue growth. Several types of bone grafting procedures are available to patients, each with its own limitations. These constraints encourage the continual development of new alternatives. Various disciplines have used L-PRF as a biological modifier in many types of surgery including periodontology, implantology, and maxillofacial surgery.³

Weinberg et al³ define a graft as “any tissue or organ used for implantation or transplantation.” Grafts can use human, animal, or synthetic substitutes to stimulate growth. They are divided into four categories based on the origin of the donor material: autografts, allografts, alloplasts, and xenografts.³

Autografts and allografts are associated with human donors. An autograft is tissue taken from and placed in the same individual. These have the highest potential for success because the tissue is obtained from the recipient. Unfortunately, this is not always an option for patients, leaving an allograft as the next option. Allografts are retrieved from one individual and placed in a different individual of the same species. They typically consist of tissue that is taken from a cadaver. Similar to the autograft, allograft studies have shown high success rates and enhanced tissue growth.³

Alloplasts are synthetic tissue substitutes, meaning they are made of nonvital materials. They offer more of a support system for surrounding structures and are present for tissue to grow around, but do not have the factors for cells to induce bone, unlike a tissue-derived graft. Alloplasts carry no risk of disease transmission and the patient does not have to undergo any additional procedures to collect donor tissue. Xenografts are tissue substitutes taken from a different species, such as bovine.³

Because these modalities are sometimes limited in their results, dentistry needs to continue evolving and discovering new treatment approaches. L-PRF is an autologous biologic modifier that is obtained from the patient’s blood. This provides a condensed network of fibrin that is saturated with cytokines, growth factors, and platelets.⁴ L-PRF speeds up the initial healing process of tissue repair. It is capable of generating both soft tissue and bone and is used in conjunction with a bone substitute or alone. There are many circumstances where tissue growth needs to be implemented for the success of a procedure.

PROCEDURE

The L-PRF procedure is relatively simple and begins with a blood draw. Approximately 9 ml to 10 ml of blood is drawn with a 24 gauge butterfly needle and then placed in a glass tube.² The glass tube is needed to achieve clot polymerization.⁵ Correct handling of the blood is a significant factor in L-PRF treatment success. The blood must be immediately transferred to a centrifuge, which is activated for approximately 12 minutes, without the addition of an anticoagulant.^6,7 During the centrifuge process, the blood coagulates and separates into three distinct layers. The bottom layer is composed of red blood cells; it is discarded. The top layer is cell-free and is also discarded. The middle layer is a mesh network that contains the majority of the platelets and fibrin. Within this middle layer, platelets lead to synthesizing growth factors in response to clotting.⁸ The fibrous middle layer also acts as a scaffold when placed for surgical dental treatment, leading to the initiation of tissue response.⁹ This layer can be compressed into a membrane or shaped into a plug depending on what treatment is needed. This clot can be converted into a membrane by compression between two sterile gauzes or by using a specific tool for collection.¹ The fibrin is easily manipulated and placed, allowing it to be used with many dental treatment options.

Once placed, the L-PRF continues to release growth factors for up to 7 days, which speeds up healing time. The cost for this procedure is lower than other options for patients because fewer materials are needed because the patient is supplying his or her own tissue (blood) for the procedure. Additionally, because the tissue is taken from the patient, its use removes the risk of infection and disease transmission, which greatly diminishes the chance of rejection.

CLINICAL APPLICATIONS

L-PRF has many clinical applications, such as soft tissue and bone regeneration, extraction socket and alveolar ridge preservation,⁶horizontal and vertical ridge augmentation, improvement of three wall infrabony defects,¹⁰ sinus lift procedures for implant placement,² periodontal tissue regeneration,¹¹ improvement of furcation defects,¹² assisting with repair of mandibular fracture sites,⁸and stimulation of enhanced repair when used in combination with bone substitute or autologous bone.^13–15

RESEARCH

Timmerman et al⁶ conducted a case study to determine the success of placing L-PRF in an extraction site to aid in alveolar ridge preservation. The study included 22 subjects who were monitored after extractions. It utilized a split-mouth randomized controlled clinical approach that compared a control group using no membrane in the extraction sites with sites undergoing the L-PRF membrane. Alveolar ridge levels of the extraction sites were compared using cone-beam computed tomography (CBCT). Each tooth was extracted and blood drawn to be centrifuged. The L-PRF membrane was isolated, compressed, and then placed in the extraction sites with subsequent suturing. Patients were prescribed a 0.12% chlorhexidine spray for use twice a day and seen 1 week later to monitor healing and remove sutures.⁶

At the follow-up appointment, patients reported discomfort following the procedure. The majority of extraction sites revealed a healing site that showed no signs of abnormality. CBCT images were taken immediately after the extraction and 3 months after treatment to track the progress. These images were then superimposed to analyze the measurement of alveolar ridge present immediately after the extraction and at the 3-month follow-up visit. Data showed that the sites where L-PRF was placed had a statistically higher success rate than those sites without. The researchers found a strong statistical correlation associated with the placement of L-PRF in extractions sites with improved healing when compared to those without.⁶ 

El Kenawy et al¹⁶ conducted a study with 15 patients that analyzed the placement of L-PRF in an extraction site while simultaneously placing an implant. Similar to other studies, each patient rinsed with chlorhexidine gluconate prior to the procedure. A flap was reflected and the tooth extracted. The socket was then irrigated and curetted thoroughly. Each site for implant insertion was continuously irrigated while being drilled to necessary dimensions based on implant size. Implants were inserted 2 mm to 3 mm beyond the original apex level to aid in stability. Following this, the space left between the socket wall and implant was packed with deproteinized bovine bone material and an L-PRF membrane positioned and sutured into place.¹⁶ 

Following treatment, each patient was prescribed 500 mg of amoxicillin for 5 days to 7 days. Oral hygiene instructions were demonstrated and a soft food diet was recommended for the next 1 week to 2 weeks. Sutures were removed 7 days post treatment and exams were scheduled every week for the following 3 weeks. At 4 months to 6 months, patients returned for healing cap placement, then 2 weeks later for abutment delivery. The implants were re-assessed every 3 months over a 1-year period. Implant success was evaluated based on stability, sulcular bleeding, peri-implant pocket depth, and radiographic findings. Results of this study revealed a 100% success rate with ideal osseointegration and a reduction in post-operative problems.¹⁶ While implant therapy is highly successful with the conventional approach, L-PRF—when used as a biological modifier—can improve wound healing and decrease discomfort post-surgery.

Sharma and Pradeep¹⁰ conducted a study on the effects of placing L-PRF in three walled bony defects in patients with chronic periodontitis. During the study, 56 defects were treated by adding L-PRF while conducting open flap de­bridement or performing open flap debridement with no addition of L-PRF. Both periodontal at­tachment levels and probing depths were documented with measurements at baseline and 9 months post-treatment. Periodontal dressing and sutures were removed after 2 weeks. A regimen of 0.12% chlorhexidine rinse was also im­plemented during this time. After 2 weeks, self-care was performed using a soft toothbrush and gentle brushing. No subgingival instrumentation occurred during the 9 months. Post-treatment values showed probing depths improved for the test group (approximately 4.55 mm vs 3.21 mm for the control group). Periodontal attachment levels also im­proved when L-PRF was added (value for the test group was 3.31 mm vs 2.77 mm in the control group). Additionally, test sites showed an approximate 48.26% greater bone production for filling the site vs 1.8% for those sites where L-PRF was not placed. When comparing the two methods of treatment, it was found that when L-PRF was used probing depths decreased, periodontal attachment level increased, and more bone was generated than when performing conventional open flap debridement.¹⁰

Sharma and Pradeep¹² evaluated the ef­fects of placing L-PRF in Class II furcation defects when conducting open flap debridement in comparison to open flap debridement alone. Thirty-six defects were treated with one of these approaches. Plaque index, sulcus bleeding index, probing depth, clinical attachment level, gingival marginal level, and radiographic bone analysis were compared using baseline and 9 month post-operative measurements. Periodontal dressing and sutures were removed after 2 weeks while using 0.12% chlorhexidine rinse during this time. Self-care was also performed using a soft toothbrush and gentle brushing. No subgingival instrumentation occurred for 9 months. The data indicated a greater reduction of probing depth was found for the L-PRF clinical group with a difference of 2.17 mm as compared with the non L-PRF control group. The test group also showed a significantly greater vertical defect fill (50.8 +/- 6.24) when compared with the control sites (16.7 +/- 6.42) at the 9-month recare appointment. Upon evaluation, both clinical and radiographic parameters indicated drastic improvement observed at those areas treated with L-PRF and open flap debridement when compared with only open flap debridement.¹²

A study by Al-Khawlani et al⁸ examined the benefits of L-PRF when placed at sites of mandibular fracture. When L-PRF was placed in close proximity to bone, enhanced bone development occurred. A group of patients ranging in age from 20 to 42 with mandibular fractures participated as subjects. The L-PRF was applied along the fracture line of the mandible, as plates were used to stabilize it. Patients were evaluated over 6 months post-surgery. The results indicated that L-PRF placement enhanced osteoblast and bone formation leading to improved healing. This autologous procedure led to a more stable bone regeneration.⁸

Sinus lifts are most commonly done so there is enough bone available to place an implant. A study by Mazor et al¹ determined the success of using L-PRF in a simultaneous sinus lift and implant placement procedure.¹ Sinus lifts are necessary when a natural tooth has been lost and the maxillary sinus, covered by the Schneiderian membrane, pneumatizes—preventing bone formation. A sinus lift is performed to lift this membrane to allow more space for bone. Additionally, bone or bone grafting material is placed to encourage bone growth in the area to stabilize the site for a future implant.¹ Typically, the graft must be placed 4 months to 6 months prior to implant placement; however, new methods are improving the success of completing both procedures at the same time.

L-PRF is useful during sinus lift procedures, especially when bone is needed for implant placement. Data were collected from 20 subjects via 25 sinus elevations and the placement of 14 implants.¹ There was no control group, but participants had to be in general good health and meet certain criteria. All implants were similar in length as well as width and there was approximately 2.9 mm of bone height remaining in each edentulous area. A full tissue flap was elevated and an ultrasonic lancet used to open a bony window. The Schneiderian membrane was delicately lifted and the bony window left attached to support the new sinus floor. This protects the sinus membrane and promotes space maintenance. Several vials of blood (72 ml) were taken from each subject and centrifuged. The PRF clots were removed and membranes compressed to be placed in each sinus. One to two PRF membranes were placed on the Schneiderian membrane in case there were any undetectable perforations created during the procedure. The implants were placed with the tips acting in a manner to hold the new sinus floor in place. One to two more PRF membranes were placed over the window before the flap was replaced to prevent invagination of the gingival mucosa. Patients were put on a 14-day chlorhexidine gluconate rinse regimen, 6 days of amoxicillin, and instructed to take ibuprofen as needed.¹

As expected, 8 days to 10 days following the procedure, a panoramic radiograph revealed no obvious change in bone density; however, 6 months later, the treated sites were filled with a dense bone-like tissue. Participants described minimal discomfort and all implants presented as stable. Six months after treatment, the procedure was deemed 100% successful by Mazor et al.¹ While some studies show that the use of implants to “tent up” the sinus membrane through elevation without L-PRF can be successful in stimulating resulting bone to fill the area, the authors concluded L-PRF was an optimal addition to this procedure to improve the natural bone regeneration around the implants.¹

Clinical results demonstrate the efficacy of L-PRF in a variety of common dental procedures. The use of L-PRF as a biological modifier stimulates tissue and leads to the im­provement of tooth support and maintenance. It is an added treatment modality to make the surgical and healing process easier on the patient. Using the patient’s own tissue greatly aids in a quicker healing time and minimal-to-no risk of infection.

CONCLUSION

As a biologic modifier, L-PRF seems to have limitless possibilities when it comes to bone and soft tissue regeneration and overall healing. Studies with control and test groups show that implant placement, as well as various other dental treatments, can still be consistently successful without the use of L-PRF, but the improved results when L-PRF is used are statistically significant. Areas for future research should investigate its use in various other bone grafting procedures such as cleft palate repair, distraction osteogenesis, and treatment of osteonecrosis of the jaw. Additionally, further research may find that this technique could be used to stimulate gingival growth and aid in the repair and/or regeneration of attachment loss caused by periodontal diseases.

One of oral health professionals’ primary objectives is to educate patients and discuss all treatment options. As such, clinicians should remain aware of viable treatment alternatives that could encourage improved outcomes. L-PRF is an advantageous technique that provides optimal results when used in conjunction with many dental procedures and is truly an asset to the dental profession.

REFERENCES

1. Mazor Z, Horowitz R, Del Corso M, Prasad H, Rohrer M, Ehrenfest D. Sinus floor augmentation with simultaneous implant placement using Choukroun’s platelet-rich fibrin as the sole grafting material: A radiologic and histologic study at 6 months. J Periodontol. 2009;80:2056–2064.
2. Castro AB, Meschi N, Temmerman A, et al. Regenerative potential of leucocyte- and platelet-rich fibrin. Part B: sinus floor elevation, alveolar ridge preservation, and implant therapy. A systematic review. J Clin Periodontol. 2017;44:225–234.
3. Weinberg, M, Westphal, C, Froum, S, et al. Comprehensive Periodontics For the Dental Hygienist. 3rd ed. New York: Julie Levin Alexander; 2010:74,398.
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6. Temmerman A, Vandessel J, Castro A, et al. The use of leucocyte and platelet-rich fibrin in socket management and ridge preservation: a split-mouth, randomized, controlled clinical trial. J Clin Periodontol. 2016;43:990–999.
7. Retna Kumar K, Genmorgan K, Abdul Rahman SM, Alaguvel Rajan M, Arul Kumar T, Srinivas Prasad V. Role of plasma-rich fibrin in oral surgery. J Pharm Bioallied Sci. 2016;8:S36–S38.
8. Al-Khawlani E, Adly O, Ahmed A, El-din El-Desouky G, Abass A, Abdelmabood A. Evaluation of platelet-rich fibrin versus platelet-rich plasma on the outcome of mandibular fracture: a comparative study. Egypt J Oral Maxillofac Surg. 2014;5:96–102.
9. Li Q, Reed D, Min L, et al. Lyophilized platelet-rich fibrin promotes craniofacial bone regeneration through runx2. Int J Mol Sci. 2014;15:8509–8525.
10. Sharma A, Pradeep AR. Treatment of 3-wall intrabony defects in patients with chronic periodontitis with autologous platelet-rich fibrin: a randomized controlled clinical trial. J Periodontol. 2011;82:1705–1712.
11. Kawase T, Okuda K, Wolff L, Yoshie H. Platelet-rich plasma-derived fibrin clot formation stimulates collagen synthesis in periodontal ligament and osteoblastic cells in vitro. J Periodontol. 2003;74:858–864.
12. Sharma A, Pradeep AR. Autologous platelet-rich fibrin in the treatment of mandibular degree II furcation defects: A randomized clinical trial. J Periodontol. 2011;82:1396–1403.
13. Reddy S, Prasad MGS, Bhowmik N, Singh S, Pandit H, Vimal SK. Vestibular incision subperiosteal tunnel access (VISTA) with platelet rich fibrin (PRF) and connective tissue graft (CTG) in the management of multiple gingival recession-a case series. Int J Appl Dent Sci. 2016;2:34–37.
14. Gupta V, Bains V, Singh GP, Mathur A, Bains R. Regenerative potential of platelet rich fibrin in dentistry: literature review. Asian J Oral Health Allied Sci. 2011;1:22–28.
15. Peck M, Marnewick J, Stephen L. Alveolar ridge preservation using leukocyte and platelet-rich fibrin: a report of a case. Case Reports in Dentistry. 2011;2011:345048.
16. EL Kenawy M, EL Shinnawi U, Salem A, et al. Efficacy of platelet rich fibrin (PRF) membrane in immediate dental implant. Mansoura Journal of Dentistry. 2014;1:78–84.

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Featured photo by MEDIAPHOTOS/ISTOCK/GETTY IMAGES PLUS 

From Dimensions of Dental Hygiene. November 2017;15(11):50-53.