Gingival recession can compromise esthetics and function of dental treatment. This article reviews the current evidence on the role of platelet-rich plasma. Clinical evidence on the use of PRP in root-coverage procedures is extremely limited.
Gingival recession can compromise esthetics and function of dental treatment. This article reviews the current evidence on the role of platelet-rich plasma. Clinical evidence on the use of PRP in root-coverage procedures is extremely limited.
Gingival recession can compromise esthetics and function of dental treatment. This article reviews the current evidence on the role of platelet-rich plasma. Clinical evidence on the use of PRP in root-coverage procedures is extremely limited.
Patients are placing increasing value on esthetic and functional outcomes of dental treatment. Gingival recession can compro- mise both esthetics and function and is a common condition, with reported prevalence as high as 50% to 88% in adults. 1 Traditional root-coverage procedures include the sub- epithelial connective tissue graft, 2 coronally advanced flap, 3 semilunar flap, 4 laterally posi- tioned flap, 5 double papilla flap, 6 and the epithelialized gingival graft. 7 Recently, dermal allografts 8,9 and guided tissue regeneration (GTR) 1012 have been introduced as alternative treatment options. Today, the subepithelial connective tissue graft procedure is still considered the gold standard for root coverage with mean per- cent root coverage varying between 65% and 98% and complete root coverage achieved in 0% to 90% of cases. 13,14 The Role of platelet-rich plasma in soft tissue root-coverage procedures: A review Jill D. Bashutski, DDS 1 /Hom-Lay Wang, DDS, MSD 2 The aim of this article was to review the current evidence on the role of platelet-rich plasma (PRP) in enhancing root-coverage techniques and discuss the rationale for its use in these applications. Sound biologic rationale and a multitude of basic science research support the use of PRP to promote soft tissue healing, although evidence of its role in enhancing periodontal applications, especially root coverage, is limited. Current scientific research has yet to elucidate all of the mechanisms by which PRP can affect soft tissue healing and assess its capacity to stimulate regeneration. Furthermore, clinical evidence on the use of PRP in root-coverage procedures is extremely limited, with only 2 randomized controlled trials published as of May 2007. A pertinent review of medical and dental literature relating to PRP and its role in wound healing and enhancement of root-coverage procedures was performed. Preliminary reports in this area suggest that the potential benefits of PRP in root-coverage procedures may be improved esthetics, decreased patient morbidity, and accelerated wound healing. An appropriate assessment of the effects of PRP and its pos- sible use in enhancing root-coverage procedures cannot be made at this time because of inadequate clinical evidence. (Quintessence Int 2008;39:473483) Key words: platelet-rich plasma, regeneration, root coverage, soft tissue grafts 1 Resident, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan. 2 Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan. Correspondence: Dr Hom-Lay Wang, Professor and Director of Graduate Periodontics, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Avenue, Ann Arbor, MI 48109-1078. Fax: 734- 936-0374. E-mail: homlay@umich.edu Bashutski.qxd 4/15/08 2:13 PM Page 473 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER 474 VOLUME 39 NUMBER 6 JUNE 2008 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang disadvantages of this technique include the need for a donor site and occasional unsatis- factory tissue contour and esthetics. 1315 In addition, complications that may arise using this technique include excessive bleeding at the donor site and infection and/or slough- ing at the receptor site. 1315 The coronally advanced flap procedure has a wide range of clinical success, with an average root coverage of 75% to 99% and complete root coverage in 23% to 95% of cases. 1619 The coronally advanced flap proce- dure has an advantage over the subepithelial connective tissue graft in that it does not require a second surgical site; however, this is at the expense of gaining tissue thickness. Similarly, root-coverage procedures utilizing GTR can achieve an average of 74% reces- sion depth coverage, with complete coverage in 41% of cases. 20 Providing soft tissue coverage of denuded root surfaces presents a unique challenge in that these surfaces are avascular, which com- plicates the healing process. Also, if soft tis- sue grafting is employed, it can be difficult to stabilize the graft against the tooth surface, resulting in sloughing and even occasional failure of the graft. 15 While traditional root- coverage procedures have adequately addressed the challenge of covering exposed roots, other factors such as esthetic accept- ability, patient morbidity, and postsurgical healing time for these grafts are sometimes suboptimal. More important, root coverage using these techniques primarily results in tis- sue repair, not regeneration. 21 As a result, new approaches to root coverage currently involve incorporating growth factors into previously employed techniques to enhance the healing response and possibly promote regeneration. Most recently, enamel matrix derivative, platelet-derived growth factor, and platelet-rich plasma (PRP) have been studied for these purposes. Although data are emerging on the ability of these factors to affect wound healing and root coverage, more long-term research is needed to fully evaluate their clinical utility. This article reviews current information on the use of PRP in soft tissue healing and root-cov- erage procedures, focusing on the biologic rationale behind its use and summarizing per- tinent studies on the subject. The search strategy included an electronic search of the Medline (PubMed) database for medical and dental literature published in the English language through May 2007. Key search terms included root coverage, coronal- ly advanced flap, connective tissue graft, gin- gival recession, platelet-rich plasma, and PRP. In addition, the bibliographies of several key papers 2224 were also reviewed and pertinent references included. The search resulted in a total of 4 clinical studies, all of which are pre- sented in the body of this article. PLATELET-RICH PLASMA Platelet-rich plasma is essentially an increased concentration of autologous platelets sus- pended in a small amount of plasma after centrifugation. Several systems have been developed to isolate PRP, all with varying platelet and growth factor yields (for a detailed review, see Roukis et al 25 ). Briefly, a small vol- ume (about 50 mL) of the patients blood is obtained and centrifuged at varying speeds until it separates into 3 layers: platelet-poor plasma, platelet-rich plasma, and red blood cells. The PRP is isolated and stored with a cit- rate-based anticoagulant until the end of the surgical procedure. Immediately before appli- cation, topical bovine thrombin and 10% cal- cium chloride are added to activate the clot- ting cascade, producing a platelet gel. The whole process takes approximately 12 min- utes 26 and produces a platelet concentration of 3 to 5 times that of native plasma. 26,27 Because the platelets are autologous, they are able to secrete bioactive growth factors upon activation and subsequent degranulation of their alpha granules. These growth factors are also present at increased concentrations in PRP and are involved in key stages of wound healing and regenerative processes including chemotaxis, proliferation, differentiation, and angiogenesis. 28 In addition to growth factors, platelets release numerous other substances that are important in wound healing. Table 1 summarizes these substances and describes the specific role of each in wound healing. Bashutski.qxd 4/15/08 2:13 PM Page 474 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER VOLUME 39 NUMBER 6 JUNE 2008 475 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang BIOLOGIC RATIONALE PRP contains a plethora of substances involved in the wound healing process that have the potential to greatly enhance soft tis- sue healing. Table 2 summarizes these mechanisms. In addition, Table 3 and Fig 1 list proposed advantages and disadvantages for the use of PRP in root-coverage applica- tions, which are elucidated forthwith. VASCULARITY Because PRP contains many growth factors that stimulate angiogenesis and increase granulation tissue formation, using PRP in combination with root-coverage procedures may be particularly advantageous (see Table 1). Vascular endothelial growth factor and platelet-derived growth factor are perhaps the most widely characterized growth factors Secreted factor Function Platelet-derived growth factor (PDGF) Accelerates deposition of wound matrix (-AA, -BB, -AB) Promotes chemotaxis of polymorphonuclear leukocytes, macrophages, fibroblasts, and smooth muscle cells Increases fibroblast and endothelial cell differentiation Enhances angiogenesis 16,39,72,73 Transforming growth factor (TGF) (-1, -2) Accelerates deposition and maturation of collagen Promotes hemotaxis of fibroblasts Stimulates collagen and fibronectin production Inhibits collagen degradation 16,39,72 Vascular endothelial growth factor (VEGF) Enhances angiogenesis 16,39,73 Fibroblast growth factor (FGF) Enhances angiogenesis 73 Epithelial cell growth factor (ECGF) Stimulates endothelial chemotaxis and promotes angiogenesis 16,39 Platelet-derived angiogenic factor (PDAF) Promotes mitogenesis of endothelial cells Enhances angiogenesis 39 Platelet factor 4 (PF4) Promotes chemotaxis for fibroblasts and monocytes Inhibits collagenase 39 Platelet-derived endothelial growth factor Stimulates mitogenesis of endothelial cells and keratinocytes 39 (PDEGF) Hepatocyte growth factor (HGF) Enhances angiogenesis Inhibits fibrosis 73 Insulin-like growth factor (IGF) Stimulates osteoblast proliferation Enhances matrix synthesis 39,72 Fibrin Cell adhesion Fibronectin Thrombus formation Vitronectin Mitogenesis Thrombospondin-1 (TSP-1) Hemostasis 39,74 Osteocalcin (Oc) Mineralization 39 Osteonectin (On) Interleukin-1 (IL-1) Activates growth factor expression in macrophages, fibroblasts, and keratinocytes 24,31 Complement Antimicrobial 74 Serotonin Primary hemostasis 74 Fibrinogen Catecholamines Adenosine Diphosphate (ADP) Adenosine Triphosphate (ATP) Factor V Von Willebrand factor VIII Thromboxane A2 Calcium Tabl e 1 Growth factors and other components of platelet-rich plasma that contribute to wound healing Bashutski.qxd 4/15/08 2:13 PM Page 475 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang secreted by platelets. Both play key roles in angiogenesis and fibroblast cell differentia- tion and are consequently very important in the wound healing process. Optimizing the blood supply to the newly covered root sur- face could theoretically allow for a greater percentage of root coverage and better soft tissue graft acceptance rates. Attaining an adequate blood supply could be particularly useful in gaining coverage of deep and wide recession defects or in minimizing sloughing where a large soft tissue graft is being placed. 15 GRAFT ACCEPTANCE AND WOUND STABILITY PRP may play a particularly important role in soft tissue grafting procedures. Compellingly, the addition of PRP improves graft adhesion and minimizes micromovement, providing the most advantageous environment for graft acceptance. 36,37 PRP also increases early wound strength 34,35 through a variety of mecha- nisms, which would help stabilize the posi- tion of a coronally advanced flap or ensure 476 VOLUME 39 NUMBER 6 JUNE 2008 Promote angiogenesis 32 Stimulate granulation tissue formation 33 Decrease inflammatory phase of wound healing 34 Increase collagen content 34,32 Increase early glycosaminoglycan (GAG) and fibronectin deposition 34 Increase early wound strength 34,35 Enhance initial epithelial migration 15 Improve hemostasis 36,37 Tabl e 2 Mechanisms by which PRP may enhance soft tissue healing Increased time of procedure Increased cost for equipment Knowledge of phlebotomy required Technique sensitive 38 A platelet count within a narrow range must be achieved for optimal results 39 Lack of long-term data and controlled trials to support efficacy Tabl e 3 Disadvantages of PRP in root-coverage procedures Platelet-rich plasma Increased vascularity Increased wound stability Increased esthetics 42 Increased regeneration potiential 40,43,45 Decreased patient morbidity Reduced tissue sloughing 26 Improved healing 26,40 Improved wound closure 15,34,36,41 Enhanced graft adhesion 37 Reduced micro- movement of graft 36 Increased tissue thickness 26 Reduced scarring 22,40,43,44 Increased healing rate 27,40,46,47 Improved hemostasis 36,37 Minimized immune response 26,49 Decreased infections Fig 1 Advantages of PRP in root-coverage procedures. Bashutski.qxd 4/15/08 2:13 PM Page 476 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER VOLUME 39 NUMBER 6 JUNE 2008 477 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang soft tissue graft acceptance. This early wound strength results from the ability of PRP to decrease the inflammatory phase of wound healing and to increase collagen con- tent and early deposition of glycosaminoglycan and fibronectin. 34 ESTHETIC OUTCOMES Increased graft acceptance rates, a greater percentage of root coverage, decreased healing time, and less sloughing of grafts would all contribute to better esthetics, both short term and long term. It has been sug- gested that PRP can also increase tissue thickness after root coverage, 15,38 thereby improving esthetics and preventing relapse of the recession since increased flap thick- ness has been correlated with better out- comes in root-coverage procedures. 50 One study comparing a coronally advanced flap to a coronally advanced flap with PRP showed a trend toward greater tissue thick- ness in the presence of PRP, although the study lacked sufficient power to detect a sig- nificant difference (P = .1). 38 To date, the abil- ity of PRP to enhance tissue thickness in soft tissue grafting procedures has not been eval- uated, nor has any mechanism been pro- posed for the observed increase in tissue thickness in the above study. This potential benefit of PRP in root-coverage procedures requires further investigation, although it shows promise. The present authors have experienced and shown 38 that PRP can enhance vascularity (due to release of vascu- lar endothelial growth factors 24 ) and promote graft adhesion and wound stability. Nonetheless, these clinical effects do not translate in enhancing percentage of root coverage or in promoting esthetic outcome when compared to sites treated without PRP. If vertical incisions are used during root- coverage procedures, potential scarring of the mucosa can be an esthetic concern, especially in patients with a high lip line. PRP may contribute to improved esthetics by min- imizing this scar formation. 22,4244 Monteleone assessed the ability of PRP to accelerate soft tissue wound healing and epithelialization of a split-thickness skin graft donor site. 44 In this study, 20 patients with side-by-side split-thick- ness graft donor sites were treated with either topical bovine thrombin or PRP in addition to an occlusive dressing. Wounds were eval- uated by direct observation, photographic morphometry, and some histopathology specimens; patient pain was also evaluated using a discomfort scale. Accelerated wound maturity and epithelialization and decreased scar formation were noted in the PRP group compared to the control group. Furthermore, patients in the PRP group reported less pain and annoyance. The possible mechanism behind de- creased scarring may be twofold. First, accel- erated wound maturation minimizes the amount of time granulation tissue is present in the surgical site. Granulation tissue forma- tion occurs in the proliferative stage of wound healing and contains collagen that is less organized and thinner than uninjured tis- sue. 51 It is necessary for wound healing, but unless the collagen reorganizes, an unsightly scar will form. Platelet-derived growth factor and epidermal growth factor, which are both present in PRP, are the main growth factors involved in fibroblast migration, proliferation, and collagen synthesis. Increased concen- trations of these growth factors are likely the reason for the accelerated wound healing, which is suggested to be at least 2 to 3 times faster than that of normal healing. 27 Second, PRP contains hepatocyte growth factor, which has powerful antifibrotic effects. Hepatocyte growth factor has been shown to reduce scar formation in various animal and human studies. 5256 Furthermore, 1 study suggested that hepatocyte growth factor may even enhance dermal regeneration in addi- tion to decreasing scar formation. 52 PRP con- tains a higher concentration of all these growth factors, which would explain the increased rate of maturation and antifibrotic effects leading to decreased scar formation. Although the biologic rationale for decreas- ing scar formation in root-coverage proce- dures exists, this has yet to be proven in stud- ies on gingival tissue. Bashutski.qxd 4/15/08 2:13 PM Page 477 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER 478 VOLUME 39 NUMBER 6 JUNE 2008 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang PATIENT MORBIDITY Patient morbidity is also an important issue to consider with root-coverage procedures. There are several reports of PRP increasing healing rates and decreasing postoperative bleeding and pain. 23,27,42,44,46,47,48 Many of the growth factors present in PRP enhance initial epithelial migration, creating a more pre- dictable soft tissue seal than with primary clo- sure alone. 15,36 One author suggests that the wound-healing process is accelerated with the use of PRP, minimizing postoperative healing time for patients and decreasing their morbid- ity. 27 However, studies utilizing PRP for other applications have revealed that PRP could not enhance wound healing, bone remodeling, or sinus augmentation. 57,58 Given that PRP has failed to show promise in other applications, the initially promising results reported in soft tissue healing during root-coverage proce- dures should be interpreted with caution until more rigorous trials are conducted. PRP has a pH of 6.5 to 6.7, which is low compared to the pH of a mature blood clot (7.0 to 7.2). 23 This lowered pH may inhibit bacterial growth and therefore decrease infection rates. Furthermore, several growth factors present in PRP are chemotactic for neutrophils, which would enhance the bodys ability to combat a developing infec- tion. However, Marx reported from his experi- ence that there was no difference in infection rates of PRP-treated bone grafts and skin wounds compared with controls. 23 The inci- dence of infection ranged between 2.0% and 3.5% for both groups. Since PRP is autologous, there is a rela- tively low risk of a negative immune reaction and disease transmission in patients who receive this product. 23,49 The only potential concern with PRP is the bovine thrombin that is frequently used to activate it. Several reports of bleeding coagulopathies exist in the litera- ture that were attributed to interactions with bovine and human factor Va, a clotting factor that binds activated platelets and is critical for prothrombin activation, after PRP applica- tion. 5961 However, within the past 10 years, the amount of bovine factor Va has been signifi- cantly reduced from 50.0 mg/mL to less than 0.2 mg/mL, thus reducing this complication. 61 REGENERATION In the field of periodontics, tissue regenera- tion is much preferred over tissue repair. While PRP has been shown to accelerate the wound-healing process and hasten repair, lit- tle is known about its ability to regenerate the soft tissues of the periodontium, although some authors suggest that it may have this potential. 27,28 Unfortunately, studies evaluat- ing the ability of PRP to promote regenera- tion in bone have shown that PRP actually has a low regenerative potential. 62,63 A signif- icant amount of data exists for the potential of growth factors found in PRP to promote regeneration. 40,6469 However, most of these studies were performed using the growth factors in isolation or in pairs, so it remains unclear what modifying effects these factors will have on each other. Some evidence of synergistic effects of different components of PRP has already been reported in the literature. 70 One recent study evaluated the effect of PRP itself on human cell lines. 71 In this in vitro study, PRP caused a marked increase in periodontal lig- ament cell proliferation, a minor increase in gingival fibroblast growth, and inhibition of keratinocyte proliferation. Also, collagen and alkaline phosphatase activity levels increased in the presence of PRP, leading the authors to conclude that PRP may promote regener- ation by differentially regulating the cell types of the periodontium. It is also important to note that platelets may secrete many other as-yet-unknown growth factors, which have an unknown effect on the regenerative potential of cells in the periodontium. An advantage of using PRP is that numer- ous growth factors are available in one product. However, this also creates a disadvantage in that the concentration of each growth factor cannot be individually customized. In addi- tion, the maximum concentration of growth factors that can be obtained in a PRP prepa- ration is not necessarily the most optimal concentration. One recent study found that fibroblast and osteoblast proliferation was optimized using a 2.5 concentration of PRP, but that further increases in concentra- tion actually reduced this proliferative effect. 39 Similar observations were found by Weibrich Bashutski.qxd 4/15/08 2:13 PM Page 478 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER VOLUME 39 NUMBER 6 JUNE 2008 479 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang and coworkers, who found that regeneration of bone around implants placed into rabbit femurs occurred only within a narrow, inter- mediate range of PRP concentration. 72 Thus, while further studies are still needed to assess the ability of PRP to stimulate regen- eration, it is already acknowledged that the inherent nature of PRP may present chal- lenges in this area because of the inability to achieve optimal levels of each growth factor with a single PRP concentration. HUMAN ROOT-COVERAGE STUDIES Evaluation of PRP and its role in augmenting root-coverage procedures is limited to 4 pub- lished reports to date (Table 4). The first case report using this technique was published in 2001, when Petrungaro used PRP as an adjunct to traditional treatment of gingival recession in 3 patients. 15 Two patients were treated using connective tissue grafts, and 1 patient was treated using a barrier mem- brane. Although complete root coverage was only obtained in 1 case, the author acknowl- edged that the gingival recession defects were difficult to treat and that complete root coverage was not an intended goal. Based on the authors clinical observations, PRP provided additional benefit to root-coverage procedures by decreasing pain and bleed- ing, increasing tissue thickness, enhancing stabilization of the graft, decreasing infection and graft sloughing, decreasing healing time, and promoting revascularization. However, it is important to note that this publication is a case report and that the clinical observations were subjective and nonquantitative. There- fore, the evidence-based conclusions that can be obtained from this study are limited since no quantitative data was presented. Griffin and Cheung used platelet-concen- trate gel in a collagen sponge carrier as an adjunct to a coronally advanced flap in the treatment of gingival recession in 2 patients. 43 Author and year Study design Results Critique Petrungaro, 2001 15 3 patients with multiple recession defects: 1/3 complete coverage, faster healing, Case report 2 PRP + SCTG less bleeding/pain, increased KG 1 PRP + GTR Griffin and 2 patients PRP + CAF Complete root coverage at 6 m, faster Case report Cheung, 2004 43 Platelet concentrate gel in sponge carrier healing, decreased inflammation, KG gain Cheung and Randomized controlled trial 80% root coverage (60% CRC) in test 2/3 examiners were Griffin, 2004 42 Miller Class I or II buccal recession in compared to 95% (65.5% CRC ) in inconsistent in 15 patients control color match test Split-mouth design SCTG or PCG 8-m follow-up Huang et al, 2005 38 Randomized controlled trial 81.0% root coverage in CAF + PRP Only Miller Class 1 23 Miller Class I buccal recession defects group (63.6% CRC) compared to recessions used CAF + PRP or CAF alone 83.5% (58.3% CRC) in the control Insufficient power to 24-w follow-up Trend toward lower WHI and GI scores detect a difference in PRP group (PRP) Platelet-rich plasma; (SCTG) subepithelial connective tissue graft; (GTR) guided tissue regeneration; (KG) keratinized gingiva; (CAF) coronally advanced flap; (PCG) platelet-concentrate grafts; (CRC) complete root coverage; (WHI) Wound Healing Index; (GI) Gingival Index. Tabl e 4 Publications evaluating the effects of PRP in root-coverage procedures Bashutski.qxd 4/15/08 2:13 PM Page 479 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER 480 VOLUME 39 NUMBER 6 JUNE 2008 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang The authors reported strikingly mature soft tissue healing at 1 week, and decreased inflammation, excellent tissue contour and color, and complete root coverage at 6 months. In 1 patient, there was a 1.5-mm gain in keratinized tissue. A lack of scar for- mation was reported, despite vertical releas- ing incisions in both cases. Again, the major drawback to this publication is that it is a case report where many of the observations were not quantified. A randomized controlled trial compared the use of platelet-concentrate grafts (PCGs) with subepithelial connective tissue grafts (SCTGs) in Miller Class I or II buccal reces- sion defects in 15 patients. 42 At 8 months, 80% root coverage (60% complete root coverage) was achieved in the PCG group compared to 95% (65.5% complete root cov- erage) in the SCTG group, although this dif- ference was not statistically significant. Notably, the control group outperformed the PCG group by 15%. In contrast, the PCG group resulted in significantly shallower probing depths (1.05 mm versus 1.79 mm). Postsurgical discomfort levels were evaluat- ed using a visual analog scale from 0 (no pain) to 10 (most pain). The group treated using PCGs had significantly less pain at 3 weeks, with a pain rating of 0.15 0.34 com- pared to 0.59 0.78 in the SCTG group, although it is questionable whether this dif- ference is clinically significant. Finally, the PCG group exhibited significant improve- ments in soft tissue contour and texture com- pared to controls. These findings were based on the observations of 3 blinded examiners who reviewed slides of the cases and scored them twice using a subjective esthetic rating of 1 (most favorable esthetics) to 4 (least favorable esthetics). Another study evaluated the effect of PRP on the coronally advanced flap procedure. 38 In this randomized controlled trial, 23 patients with Miller Class I buccal recession defects were treated with either PRP plus coronally advanced flap or coronally advanced flap alone and followed for 24 weeks postsurgery. Mean root coverage was 81.0% (63.6% complete root coverage) in the coronally advanced flap plus PRP group compared to 83.5% (58.3% complete root coverage) in the control group, which was not significantly different. PRP-treated recession defects resulted in lower Gingival Index 73 scores, although this was not statistically sig- nificant. A Wound Healing Index 38 was devel- oped for this study, which scored the tissue healing on a scale from 1 (uneventful healing) to 3 (poor wound healing). At 2 weeks, the PRP group had lower Wound Healing Index scores than did controls, although this also was not statistically significant and this effect was no longer seen at 1 month. However, the authors suggested that this lack of signifi- cance may be due to small sample sizes and the fact that only Miller Class I recession defects were studied and these respond well to most root-coverage techniques. CONCLUSION Using PRP as an adjunct to root-coverage pro- cedures is a relatively new phenomenon, although PRP has been used to promote wound healing and hemostasis in medical and dental applications for many years. Specifically, PRP has been used most com- monly in sinus augmentation procedures, 74 esthetic plastic surgery, 75 and spinal surgery. 76 Preliminary reports suggest that the potential benefits of PRP in root-coverage procedures may be improved esthetics, decreased patient morbidity, and accelerated wound healing. Further investigation of this technique is war- ranted with larger sample sizes, more chal- lenging defects, and histologic data to better determine the value of PRP as an adjunct to traditional root-coverage procedures. At this point, sufficient long-term evidence and rigor- ous clinical studies to support the use of PRP for this purpose are lacking. Although PRP may show promise in this area, there is insuffi- cient evidence to support its use at this time. ACKNOWLEDGMENT This work was partially supported by the University of Michigan Periodontal Graduate Student Research Fund. Bashutski.qxd 4/15/08 2:13 PM Page 480 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER VOLUME 39 NUMBER 6 JUNE 2008 481 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang REFERENCES 1. Kassab MM, Cohen RE. The etiology and prevalence of gingival recession. J Am Dent Assoc 2003;134: 220225. 2. Langer B, Langer L. Subepithelial connective tissue graft technique for root coverage. J Periodontol 1985;56:715720. 3. Restrepo OJ. Coronally repositioned flap: Report of four cases. J Periodontol 1973;44:564567. 4. Tarnow DP. Semilunar coronally repositioned flap. J Clin Periodontol 1986;13:182185. 5. Grupe H, Warren R. Repair of gingival defects by a sliding flap operation. J Periodontol 1956;27: 290295. 6. Cohen DW, Ross SE. The double papillae reposi- tioned flap in periodontal therapy. J Periodontol 1968;39:6570. 7. Nabers JM. Free gingival grafts. Periodontics 1966; 4:243245. 8. Mahn DH. Esthetic correction of gingival recession using a modified tunnel technique and an acellular dermal connective tissue allograft. J Esthet Restor Dent 2002;14:1823. 9. Harris RJ. Cellular dermal matrix used for root cov- erage: 18-month follow-up observation. Int J Periodontics Restorative Dent 2002;22:156163. 10. Pini Prato G, Clauser C, Cortellini P,Tinti C, Vincenzi G, Pagliaro U. Guided tissue regeneration versus mucogingival surgery in the treatment of human buccal recessions. A 4-year follow-up study. J Periodontol 1996;67:12161223. 11. Tinti C, Vincenzi G, Cortellini P, Pini Prato G, Clauser C. Guided tissue regeneration in the treatment of human facial recession. A 12-case report. J Periodontol 1992;63:554560. 12. Wang HL, Pappert TD, Castelli WA, Chiego DJ Jr, Shyr Y, Smith BA. The effect of platelet-derived growth factor on the cellular response of the periodontium: An autoradiographic study on dogs. J Periodontol 1994;65:429436. 13. Roccuzzo M, Bunino M, Needleman I, Sanz M. Periodontal plastic surgery for treatment of local- ized gingival recessions: A systematic review. J Clin Periodontol 2002;29(suppl 3):178194. 14. Clauser C, Nieri M, Franceschi D, Pagliaro U, Pini- Prato G. Evidence-based mucogingival therapy. Part 2: Ordinary and individual patient data meta-analy- ses of surgical treatment of recession using com- plete root coverage as the outcome variable. J Periodontol 2003;74:741756. 15. Petrungaro PS. Using platelet-rich plasma to accel- erate soft tissue maturation in esthetic periodontal surgery. Compend Contin Educ Dent 2001;22: 729732, 734, 736 passim. 16. de Sanctis M, Zucchelli G. Coronally advanced flap: A modified surgical approach for isolated reces- sion-type defects: Three-year results. J Clin Periodontol 2007;34:262268. 17. Spahr A, Haegewald S, Tsoulfidou F, et al. Coverage of Miller class I and II recession defects using enam- el matrix proteins versus coronally advanced flap technique: A 2-year report. J Periodontol 2005;76: 18711880. 18. Wennstrom JL. Mucogingival therapy. Ann Perio- dontol 1996;1:671701. 19. Greenwell H, Bissada NF, Henderson RD, Dodge JR. The deceptive nature of root coverage results. J Periodontol 2000;71:13271337. 20. Al-Hamdan K, Eber R, Sarment D, Kowalski C, Wang HL. Guided tissue regeneration-based root coverage: Meta-analysis. J Periodontol 2003;74:15201533. 21. Trombelli L. Periodontal regeneration in gingival recession defects. Periodontol 2000 1999;19: 138150. 22. Anitua E, Sanchez M, Nurden AT, Nurden P, Orive G, Andia I. New insights into and novel applications for platelet-rich fibrin therapies. Trends Biotechnol 2006;24:227234. 23. Marx RE. Platelet-rich plasma: Evidence to support its use. J Oral Maxillofac Surg 2004;62:489496. 24. Pietrzak WS, Eppley BL. Platelet rich plasma: Biology and new technology. J Craniofac Surg 2005;16: 10431054. 25. Roukis TS, Zgonis T, Tiernan B. Autologous platelet- rich plasma for wound and osseous healing: A review of the literature and commercially available products. Adv Ther 2006;23:218237. 26. Petrungaro P. Platelet-rich plasma for dental implants and soft-tissue grafting. Interview by Arun K. Garg. Dent Implantol Update 2001;12:4146. 27. Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:638646. 28. Cochran DL, Wozney JM. Biological mediators for periodontal regeneration. Periodontol 2000 1999; 19:4058. 29. Grageda E. Platelet-rich plasma and bone graft materials: A review and a standardized research protocol. Implant Dent 2004;13:301309. 30. Distler JH, Hirth A, Kurowska-Stolarska M, Gay RE, Gay S, Distler O. Angiogenic and angiostatic factors in the molecular control of angiogenesis. Q J Nucl Med 2003;47:149161. 31. Broughton G 2nd, Janis JE, Attinger CE. Wound heal- ing: An overview. Plast Reconstr Surg 2006;117 (suppl):1e-S32e-S. 32. Green DM, Klink B. Platelet gel as an intraoperative- ly procured platelet-based alternative to fibrin glue. Plast Reconstr Surg 1998;101:11611162. 33. Mustoe TA, Pierce GF, Morishima C, Deuel TF. Growth factorinduced acceleration of tissue repair through direct and inductive activities in a rabbit dermal ulcer model. J Clin Invest 1991;87:694703. Bashutski.qxd 4/15/08 2:13 PM Page 481 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER 482 VOLUME 39 NUMBER 6 JUNE 2008 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang 34. Pierce GF, Tarpley JE, Yanagihara D, Mustoe TA, Fox GM,Thomason A. Platelet-derived growth factor (BB homodimer), transforming growth factor-beta 1, and basic fibroblast growth factor in dermal wound healing. Neovessel and matrix formation and cessa- tion of repair. Am J Pathol 1992;140:13751388. 35. Murray MM, Spindler KP, Devin C, et al. Use of a col- lagenplatelet rich plasma scaffold to stimulate healing of a central defect in the canine ACL. J Orthop Res 2006;24:820830. 36. Whitman DH, Berry RL, Green DM. Platelet gel: An autologous alternative to fibrin glue with applica- tions in oral and maxillofacial surgery. J Oral Maxillofac Surg 1997;55:12941299. 37. Carlson NE, Roach RB Jr. Platelet-rich plasma: Clinical applications in dentistry. J Am Dent Assoc 2002; 133:13831386. 38. Huang LH, Neiva RE, Soehren SE, Giannobile WV, Wang HL. The effect of platelet-rich plasma on the coronally advanced flap root coverage procedure: A pilot human trial. J Periodontol 2005;76:17681777. 39. Graziani F, Ivanovski S, Cei S, Ducci F, Tonetti M, Gabriele M. The in vitro effect of different PRP con- centrations on osteoblasts and fibroblasts. Clin Oral Implants Res 2006;17:212219. 40. Park JB, Matsuura M, Han KY, et al. Periodontal regeneration in class III furcation defects of beagle dogs using guided tissue regenerative therapy with platelet-derived growth factor. J Periodontol 1995; 66:462477. 41. Anitua E. Plasma rich in growth factors: Preliminary results of use in the preparation of future sites for implants. Int J Oral Maxillofac Implants 1999;14: 529535. 42. Cheung WS, Griffin TJ. A comparative study of root coverage with connective tissue and platelet con- centrate grafts: 8-month results. J Periodontol 2004; 75:16781687. 43. Griffin TJ, Cheung WS. Treatment of gingival reces- sion with a platelet concentrate graft: A report of two cases. Int J Periodontics Restorative Dent 2004; 24:589595. 44. Monteleone K, Marx RE, Ghurani R. Wound repair/Cosmetic surgery healing enhancement of skin graft donor sites with platelet-rich plasma (PRP). Presented at the 82nd Annual American Academy of Oral and Maxillofacial Surgery Meeting, San Francisco, 2000. 45. Anitua E, Sanchez M, Nurden AT, et al. Autologous fibrin matrices: A potential source of biological mediators that modulate tendon cell activities. J Biomed Mater Res A 2006;77:285293. 46. Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 2004;91:415. 47. Garg AK. The use of platelet-rich plasma to enhance the success of bone grafts around dental implants. Dent Implantol Update 2000;11:1721. 48. Mancuso JD, Bennion JW, Hull MJ, Winterholler BW. Platelet-rich plasma: A preliminary report in routine impacted mandibular third molar surgery and the prevention of alveolar osteitis. J Oral Maxillofac Surg 2003;61:40. 49. Ogino Y, Ayukawa Y, Tsukiyama Y, Koyano K. The effect of platelet-rich plasma on the cellular response of rat bone marrow cells in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;100: 302307. 50. Hwang D, Wang HL. Flap thickness as a predictor of root coverage: A systematic review. J Periodontol 2006;77:16251634. 51. Forrest L. Current concepts in soft connective tissue wound healing. Br J Surg 1983;70:133140. 52. Ono I, Yamashita T, Hida T, et al. Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds. J Surg Res 2004;120:4755. 53. Ha X, Li Y, Lao M, Yuan B, Wu CT. Effect of human hepatocyte growth factor on promoting wound healing and preventing scar formation by aden- ovirus-mediated gene transfer. Chin Med J (Engl) 2003;116:10291033. 54. Herrero-Fresneda I, Torras J, Franquesa M, et al. HGF gene therapy attenuates renal allograft scarring by preventing the profibrotic inflammatory-induced mechanisms. Kidney Int 2006;70:265274. 55. Tarnawski AS. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 2005;50 (suppl 1):S2433. 56. Tarnawski A. Molecular mechanisms of ulcer heal- ing. Drug News Perspect 2000;13:158168. 57. Thor A, Wannfors K, Sennerby L, Rasmusson L. Reconstruction of the severely resorbed maxilla with autogenous bone, platelet-rich plasma, and implants: 1-year results of a controlled prospective 5-year study. Clin Implant Dent Relat Res 2005; 7:209220. 58. Raghoebar GM, Schortinghuis J, Liem RS, Ruben JL, van der Wal JE, Vissink A. Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor? Clin Oral Implants Res 2005;16:349356. 59. Cmolik BL, Spero JA, Magovern GJ, Clark RE. Redo cardiac surgery: Late bleeding complications from topical thrombin-induced factor V deficiency. J Thorac Cardiovasc Surg 1993;105:222227. 60. Muntean W, Zenz W, Finding K, Zobel G, Beitzke A. Inhibitor to factor V after exposure to fibrin sealant during cardiac surgery in a two-year-old child. Acta Paediatr 1994;83:8487. 61. Christie RJ, Carrington L, Alving B. Postoperative bleeding induced by topical bovine thrombin: Report of two cases. Surgery 1997;121:708710. 62. Sanchez AR, Sheridan PJ, Eckert SE, Weaver AL. Regenerative potential of platelet-rich plasma added to xenogenic bone grafts in peri-implant defects: A histomorphometric analysis in dogs. J Periodontol 2005;76:16371644. Bashutski.qxd 4/15/08 2:13 PM Page 482 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER VOLUME 39 NUMBER 6 JUNE 2008 483 QUI NTESSENCE I NTERNATI ONAL Bashut ski /Wang 63. Casati MZ, de Vasconcelos Gurgel BC, Goncalves PF, et al. Platelet-rich plasma does not improve bone regeneration around peri-implant bone defectsA pilot study in dogs. Int J Oral Maxillofac Surg 2007;36:132136. 64. Lynch SE, Buser D, Hernandez RA, et al. Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs. J Periodontol 1991;62:710716. 65. Lynch SE, Williams RC, Polson AM, et al. A combina- tion of platelet-derived and insulin-like growth fac- tors enhances periodontal regeneration. J Clin Periodontol 1989;16:545548. 66. Rutherford RB, Niekrash CE, Kennedy JE, Charette MF. Platelet-derived and insulin-like growth factors stimulate regeneration of periodontal attachment in monkeys. J Periodontal Res 1992;27:285290. 67. Cho MI, Lin WL, Genco RJ. Platelet-derived growth factormodulated guided tissue regenerative ther- apy. J Periodontol 1995;66:522530. 68. Giannobile WV, Hernandez RA, Finkelman RD, et al. Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individu- ally and in combination, on periodontal regenera- tion in Macaca fascicularis. J Periodontal Res 1996; 31:301312. 69. Giannobile WV, Finkelman RD, Lynch SE. Comparison of canine and non-human primate ani- mal models for periodontal regenerative therapy: Results following a single administration of PDGF/ IGF-I. J Periodontol 1994;65:11581168. 70. Strayhorn CL, Garrett JS, Dunn RL, Benedict JJ, Somerman MJ. Growth factors regulate expression of osteoblast-associated genes. J Periodontol 1999; 70:13451354. 71. Annunziata M, Oliva A, Buonaiuto C, et al. In vitro cell-type specific biological response of human periodontally related cells to platelet-rich plasma. J Periodontal Res 2005;40:489495. 72. Weibrich G, Hansen T, Kleis W, Buch R, Hitzler WE. Effect of platelet concentration in platelet-rich plas- ma on peri-implant bone regeneration. Bone 2004;34:665671. 73. Loe H. The Gingival Index, the Plaque Index and the Retention Index Systems. J Periodontol 1967;38 (suppl):610616. 74. Boyapati L, Wang HL. The role of platelet-rich plas- ma in sinus augmentation: A critical review. Implant Dent 2006;15:160170. 75. Bhanot S, Alex JC. Current applications of platelet gels in facial plastic surgery. Facial Plast Surg 2002;18:2733. 76. Bose B, Balzarini MA. Bone graft gel: Autologous growth factors used with autograft bone for lumbar spine fusions. Adv Ther 2002;19:170175. Bashutski.qxd 4/15/08 2:13 PM Page 483 COPYRIGHT 2008 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER