Platelet-rich plasma: a promising innovation in dentistry

The goal of periodontal therapy is to protect and maintain the patient's natural dentition for his or her lifetime. More specifically, after periodontal regenerative surgery, the aim is to achieve complete wound healing and regeneration of the periodontal unit. A recent innovation in dentistry is the preparation and use of platelet-rich plasma (PRP), a concentrated suspension of the growth factors found in platelets. These growth factors are involved in wound healing and are postulated as promoters of tissue regeneration. This clinical update outlines the specific effects of these growth factors, both in vitro and in vivo, on periodontal wound healing. The review focuses on current animal and human trials using PRP to promote tissue regeneration and alveolar bone repair. The article goes on to describe the clinical benefits of PRP and the step-by-step preparation of PRP in the dental office.     

Growth factor modulation of fibroblasts in simulated wound healing

Growth factors are potent bioactive molecules responsible for the co-ordination of many cell functions and interactions. Of these agents PDGF and IGF have shown particular promise as agents which may be used to stimulate periodontal regeneration. In order to further understand the mechanisms by which growth factors may work, a simple model of in vitro wound healing has been utilized to assess the effects of PDGF on human periodontal ligament fibroblasts and its potential to stimulate wound healing. Human periodontal ligament fibroblasts were plated into 24-well plates and upon reaching confluence were wounded by creating uniform discoid lesions stripped of cells. The influence of various concentrations of PDGF on cell proliferation, cell migration and extracellular matrix synthesis was monitored. The results of this study indicated that in the presence of 10 ng/ml PDGF and 0.2% fetal calf serum, both cell proliferation and cell migration were significantly stimulated. In the wounded cultures, PDGF appeared to cause a moderate stimulation of proteoglycan synthesis compared to unwounded cultures. In conclusion, the model system tested appears to be useful for studying fundamental cellular and biochemical events associated with wound healing. The effects of PDGF in this system confirm that it is capable of modulating fibroblasts in a manner compatible with the events associated with wound repair.     

Autogenous platelet-rich plasma in combination with bovine-derived hydroxyapatite xenograft for treatment of a cystic lesion of the jaw

In the last 5 years, many studies about autogenous platelet-rich plasma have been undertaken pointing out its regenerative and reparative properties on tissues. The features of this product are an attribute of platelet cells, which, after cellular interactions, release growth factors. These molecules promote tissue healing and also induce cellular regeneration. Bone is a dynamic tissue subject to balanced processes of bony formation and reabsorption; autologous platelet gel or concentrate (PRP) can be used alone or in association with bony graft for the treatment of bony defect, cystic lesions, alveolar bone defects, and periodontal pockets. Its application fields are oral and maxillofacial surgery, plastic surgery, and general surgery, and it can be applied particularly in patients with coagulation diseases. In our experience, a giant cystic lesion of the jaw was treated with PRP and granules of bovine-derived hydroxyapatite xenograft to enhance bony regeneration and promote tissue healing.     

Effect of platelet-rich plasma on bone regeneration in dentistry: a systematic review

Objective: To review systematically the reported effects of platelet‐rich plasma (PRP) on bone regeneration. Material and methods: Up to June 2006, MEDLINE and Cochrane databases were explored with different combinations of three search terms: ‘PRP’, ‘bone regeneration’, ‘dentistry’ and their synonyms. Inclusion criteria: human controlled clinical trials designed to treat maxillofacial bony defects with application of PRP (test) or without PRP (control), including at least five patients with a follow‐up period of more than 3 months and using clinical assessment, radiography, histology and/or histomorphometry for evaluation. Literature search, selection of eligible articles and data extraction were carried out independently by two readers. Results: The literature search revealed 108 references, of which 17 were selected for further analysis. Finally, nine articles fulfilling the inclusion criteria were selected for systematically review. Owing the substantial heterogeneity of the studies it was not possible to analyze the data statistically. An attempt was made to compare results from studies that used similar outcome measures by calculating and adding confidence intervals to the data presented in the original papers. Differences in treatment effects for periodontal defects in terms of clinical attachment level (CAL) were significant (ranging from 0.8 to 3.2 mm). The reported effects of PRP in sinus elevation (compared with their controls) were <10%. Conclusion: We found evidence for beneficial effects of PRP in the treatment of periodontal defects. Evidence for beneficial effects of PRP in sinus elevation appeared to be weak. No conclusions can be drawn about other applications of PRP in dentistry.     

Lysophosphatidic acid modulates the regenerative responses of human gingival fibroblasts and enhances the actions of platelet-derived growth factor

BACKGROUND: Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF is known to interact extensively with another platelet mediator, lysophosphatidic acid (LPA), to enhance regenerative responses in non-oral systems. PDGF and LPA are both liberated by platelets in the blood clot, which is known to be critical in stabilizing early periodontal wound healing. The purpose of this study was to evaluate the basic interactions of LPA with primary human gingival fibroblasts (GF) alone and with PDGF-BB for promoting GF growth and migration, as well as their effects in an in vitro oral wound-healing model. METHODS: GF regenerative responses were measured using 1 and 10 microM LPA in the absence or presence of 1 or 10 ng/ml PDGF-BB. Cell growth was determined using [3H]thymidine incorporation and cell counting. Migration responses were measured using a microchemotaxis chamber. For the in vitro wound-healing experiments, GF were grown to confluence on glass slides, and a 3 mm wide wound was mechanically inflicted. Percent wound fill on days 4, 6, and 9 was analyzed using computer-assisted histomorphometry. RESULTS: GF exhibited proliferative and chemotactic responses to LPA. These responses were synergistic when LPA and PDGF-BB were present together. LPA on its own did not stimulate statistically significant wound fill, but when combined with PDGF-BB, wound fill was equivalent to the 10% serum positive control group by day 6 (5.5-fold of negative control, [P<0.001]) and again on day 9 (6-fold of negative control, [P<0.001]). CONCLUSIONS: These studies provide the first evidence that LPA stimulates human GF regenerative responses and that it interacts positively with PDGF-BB to regulate these actions. The results suggest that LPA needs to be further investigated in the oral system as a factor that should be considered for incorporation when designing new periodontal wound-healing therapies using PDGF.     

Bone growth factors in maxillofacial skeletal reconstruction

A literature review was performed to survey the available information on the potential of bone growth factors in skeletal reconstruction in the maxillofacial area. The aim of this review was to characterize the biological and developmental nature of the growth factors considered, their molecular level of activity and their osteogenic potential in craniofacial bone repair and reconstruction. A total of 231 references were selected for evaluation by the content of the abstracts. All growth factors considered have a fundamental role in growth and development. In postnatal skeletal regeneration, PDGF plays an important role in inducing proliferation of undifferentiated mesenchymal cells. It is an important mediator for bone healing and remodelling during trauma and infection. It can enhance bone regeneration in conjunction with other growth factors but is unlikely to provide entirely osteogenic properties itself. IGFs have an important role in general growth and maintenance of the body skeleton. The effect of local application of IGFs alone in craniofacial skeletal defects has not yet shown a clear potential for enhancement of bone regeneration in the reported dosages. The combination of IGF-I with PDGF has been effective in promoting bone regeneration in dentoalveolar defects around implants or after periodontal bone loss. TGFbeta alone in skeletal reconstruction appears to be associated with uncertain results. The presence of committed cells is required for enhancement of bone formation by TGFbeta. It has a biphasic effect, which suppresses proliferation and osteoblastic differentiation at high concentrations. BMPs, BMP2, BMP4 and BMP7 in particular, appear to be the most effective growth factors in terms of osteogenesis and osseous defect repair. Efficacy of BMPs for defect repair is strongly dependent on the type of carrier and has been subject to unknown factors in clinical feasibility trials resulting in ambiguous results. The current lack of clinical data may prolong the period until this factor is introduced into routine clinical application. PRP is supposed to increase proliferation of undifferentiated mesenchymal cells and to enhance angiogenesis. There is little scientific evidence about the benefit of PRP in skeletal reconstructive and preprosthetic surgery yet and it is unlikely that peri-implant bone healing or regeneration of local bone into alloplastic material by the application of PRP alone will be significantly enhanced.     

Chlorhexidine in Dentistry: Pharmacology,Uses, and Adverse Effects

ObjectivesThe aim of this work was to review the current uses of chlorhexidine (CHX) in dentistry based on its mechanism of action, whilst highlighting the most effective protocols that render the highest clinical efficacy whilst limiting adverse drug reactions.MethodsA literature search was conducted using the key words chlorhexidine, mechanism of action, adverse effects, and dentistry using databases in the University of Toronto library system. The titles and abstracts were read, and relevant articles were selected.ResultsA total of 1100 publications were identified, 100 were investigated, and 67 of them were used. Out of the 67 selected articles, 12 were reviews on CHX; 5 articles focussed on CHX gels; 13 focussed on CHX mouthwashes; 8 focussed on CHX products; 13 discussed adverse effects associated with CHX; 13 focussed on periodontal pathology and treatment; 6 focussed on implant periodontal and dental surgeries; 7 evaluated effects on caries; 6 looked at the mechanisms of action; and 12 focussed on the antibacterial and antimicrobial impact on the oral biome. There were multiple areas of overlap amongst the articles, and results showed that CHX provides different uses, but mainly as an adjunct to various treatments. Mouthwash was the most superior medium when used in short time spans when mechanical prophylaxis was not possible for the prevention of gingivitis and maintenance of oral hygiene. CHX products are often used in periodontics, post–oral surgical procedures, and as a prophylaxis for multiple invasive procedures with minimal adverse effects. Tooth staining was the most negative adverse effect reported by patients.ConclusionsCHX's antimicrobial properties make it an ideal prophylactic when mechanical debridement is not possible. CHX mouthwash appears to be more effective compared to gels. Concentrations of 0.12% to 0.2% are recommended; any mouthwash with concentrations above 0.2% will unnecessarily increase the unwanted side effects. CHX is useful amongst various areas of dentistry including oral surgery, periodontics, and even general dentistry. For long-term treatments, especially in periodontitis patients (stage I-III) undergoing nonsurgical treatments, CHX chips are recommended. CHX chips are also recommended as an adjunct to implant debridement in patients with peri-implant mucositis and peri-implantitis over CHX mouthwash and gels.     

Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet-derived growth factor

BACKGROUND: Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF interacts extensively with lysophosphatidic acid (LPA). We recently showed that LPA modulates the responses of human gingival fibroblasts to PDGF. The objectives of this study were as follows: 1) to evaluate the basic interactions of LPA with primary human periodontal ligament fibroblasts (PDLFs) alone and with PDGF-BB for promoting PDLF growth and migration; 2) to determine the effects in an in vitro oral wound-healing model; and 3) to identify the LPA receptors (LPARs) expressed by PDLF. METHODS: PDLF regenerative responses were measured using 1 and 10 microM LPA in the absence or presence of 1 or 10 ng/ml PDGF. Cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and by cell counting. Migration responses were measured using a microchemotaxis chamber. PDLFs were grown to confluence on glass slides, a 3-mm-wide wound was mechanically inflicted, and wound fill on days 4, 6, and 9 was reported. PDLF LPAR expression was determined using Western blotting. RESULTS: PDLFs exhibited proliferative and chemotactic responses to LPA; these responses were enhanced when LPA and PDGF were present together. LPA plus PDGF elicited complete wound fill. PDLFs express the LPARs LPA(1), LPA(2), and LPA(3). CONCLUSIONS: To our knowledge, this study provides the first evidence that LPA stimulates human PDLF wound healing responses and interacts positively with PDGF to regulate these actions. These results suggest that LPA and its receptors play important modulatory roles in PDLF regenerative biology.     

Suturing for optimal soft tissue management

For optimal postsurgical wound healing, non-tension primary wound closure of various soft tissue flaps must be established. Surgical procedures that require clinical flap manipulation (such as those used with traditional periodontal therapy, periodontal plastic cosmetic surgery, hard and soft tissue regeneration, and the excision of pathologic tissue) also require excellent execution and a thorough understanding of the various techniques of surgery, suturing, and the materials currently available for the desired clinical results. This article discusses the rationale behind specific suturing techniques and suture materials to aid the clinician with optimal wound closure.     

A review of dental suturing for optimal soft-tissue management

Establishing nontension primary wound closure of various soft-tissue flaps is paramount for optimal postsurgical wound healing. Surgical procedures that require clinical flap manipulation such as those used with traditional periodontal therapy, periodontal plastic cosmetic surgery, hard- and soft-tissue regeneration, and the excision of pathologic tissue also require excellence in execution and thorough understanding of the various techniques of surgery, suturing, and the materials currently available to ensure the desired clinical results. This article will discuss the rationale of specific suturing techniques and suture materials to aid the clinician in obtaining optimal wound closure.     

Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitro

Bertrand‐Duchesne M‐P, Grenier D, Gagnon G. Epidermal growth factor released from platelet‐rich plasma promotes endothelial cell proliferation in vitro. J Periodont Res 2009; doi: 10.1111/j.1600‐0765.2009.01205.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective: The therapeutic benefits of platelet‐rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. Material and Methods: The levels of vascular endothelial growth factor (VEGF), platelet‐derived growth factor BB (PDGF‐BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium‐ and thrombin‐activated PRP samples from five donors were quantified by enzyme‐linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody‐coated beads on HUVEC proliferation was also tested. Results: Average concentrations of VEGF, PDGF‐BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody‐coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose‐dependent manner. Conclusion: This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds.     

Platelet-rich plasma-derived fibrin clot formation stimulates collagen synthesis in periodontal ligament and osteoblastic cells in vitro

BACKGROUND: Platelet-rich plasma (PRP) contains several growth factors, including platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), at high levels. We have demonstrated the PRP functions like TGF-beta to modulate cell proliferation in a cell-type specific manner. In addition, PRP forms gel-like materials in several, but not all, cell cultures tested. This study was designed to investigate PRP's action on extracellular matrix production in periodontal ligament (PDL) and osteoblastic MG63 cell cultures. METHODS: PRP was prepared from the plasma obtained from autologous blood of healthy volunteers and stored at -20 degrees C until used. Cells treated with PRP (0.5% to 2%) were immunocytochemically stained for type I collagen and fibrin and the viscosity of the culture media was visually evaluated. Fibrinogen in PRP was detected by immunodot-blotting while endogenous thrombin expression in cells was detected by a modified enzyme-linked immunosorbent assay. RESULTS: Gel-like material rapidly (< 30 minutes) formed in cultures of either PDL or osteoblastic MG63 cell cultures after addition of PRP (> or = 0.5%). PRP changed cell shape and up-regulated type I collagen at 24 hours. Fibrinogen was detected in the PRP preparations and insoluble fibrin networks were found in the newly formed gel-like material. PRP's action on collagen synthesis was mimicked by purified fibrinogen and blocked by thrombin inhibitor. Thrombin was expressed both in PDL and MG63 cells. CONCLUSIONS: These findings demonstrated that the gel-like material formed in cell cultures of either PDL or MG63 cells is fibrin clot that is capable of up-regulating collagen synthesis in the extracellular matrix. Our data suggest the possibility that fibrinogen, converted to fibrin, in combination with growth factors present in PRP might effectively promote wound healing at sites of injury in periodontal tissue.     

国内外口腔颌面外科教育培训体系对比

口腔颌面外科的范围除了基础的牙及牙槽外科之外,还包括各种复杂的颅颌面手术,因此对口腔颌面外科医生的知识背景要求就不仅限于牙科。虽然其在世界范围的很多地方被归为牙科专业,但也有许多国家会要求从业者获得临床医学和牙科学的双重学位。不同国家和地区的口腔颌面外科教育培训路径各有不同,文章将进行对比分析,并浅谈对于口腔颌面外科医师培养的一些思考。     

2001-2006年国内循证口腔医学文献分析

目的:对2001-2006年国内专业期刊发表的循证口腔医学文献进行分析。方法:利用清华同方知网技术产业集团出版的CNKI数据库为主要检索工具,以关键词和主题词检索出2001-2006年国内期刊发表的有关循证口腔医学论文,应用文献计量学方法对其进行分析。结果:检出论文74篇,文献基本呈逐年增长趋势。循证口腔医学研究热点为口腔黏膜病及口腔颌面外科疾病等,国内刊登循证医学文献的主要期刊是《中国循证医学杂志》、《中华口腔医学杂志》、《中国口腔颌面外科杂志》。结论:迄今为止,相当一部分为重复性的循证医学介绍,创新性不强,深入研究不够,采用Meta分析的文献极为少见。     

Treatment of periapical inflammatory lesion with the combination of platelet-rich plasma and tricalcium phosphate: a case report

Periapical surgery is an important treatment alternative in the presence of a periapical inflammatory lesion. To achieve optimal healing and regeneration of the bone, different bone substitutes or barrier membranes can be used after degranulation of the lesion. Tricalcium phosphate (TCP) graft material is one of these substitutes. Platelet Rich Plasma (PRP) preparation is a new biotechnology and can be used in many different surgical procedures. It consists of thrombocyte concentrates and high amounts of growth factors (GFs), especially platelet derived growth factor (PDGF), insulin-like growth factor (IGF-I) and transforming growth factor (TGF-beta), which are important in wound healing and regeneration. In this case report, use of platelet gel in conjunction with TCP in the treatment of periapical inflammatory lesion and the results of 12 months has been reported.     

Platelet Concentrates: Past,Present and Future

Platelets play a crucial role in hemostasis and wound healing, platelet growth factors are well known source of healing cytokines. Numerous techniques of autologous platelet concentrates have been developed and applied in oral and maxillofacial surgery. This review describes the evolution of the first and second generation of platelet concentrates (platelet rich plasma and platelet rich fibrin respectively) from their fore runner-fibrin sealants.     

Immunolocalization of platelet-derived growth factor A and B chains and PDGF-α and β receptors in human gingival wounds

Platelet-derived growth factor (PDGF) is a polypeptide growth factor which has been implicated as a major mitogen involved in wound healing. The PDGF appears to promote periodontal regeneration; however, its distribution in gingival tissues is not known and how it participates in gingival wound healing is unclear. Using highly specific antibodies we have studied the distribution of PDGF A and B chains and α- and β-PDGF receptors in healing human gingival wounds. Wounds were created by making a 0.75 mm deep incision in the papilla of healthy human gingiva and biopsies were obtained from the same site after 8 h and 1, 3, 7, 14 and 21 d. Frozen sections were immunostained with affinity purified antibodies. The results showed that both epithelium and fibrin clot manifested positive immunostaining for anti-PDGF-A and B-chain antibodies. Staining was present in unwounded and wounded epithelia, and in the fibrin clot it appeared to be more intense for the PDGF-A chain. Blood vessels in connective tissue were also positive while other areas were largely negative. No significant staining was detectable in healthy tissues for anti-PDGF-α or -β receptor antibodies. However, the wound site began to manifest positive immunostaining for anti-β-receptor antibody after 3 d of healing, became maximal at 7d, and then decreased. Our data indicate, but do not prove, that gingival epithelium may be a source of PDGF A and B chains and that the A chain may have a more prominent role to play during early stages of healing. Expression of PDGF β-receptor appears later at the wound site, indicating that the PDGF B isomer may regulate later wound healing events.     

Platelet rich plasma (PRP): potentialities and techniques of extraction

This paper describes the various techniques of platelet-rich plasma (PRP) extraction codified in recent years and their use potential is evaluated. PRP is one of the techniques with which at the moment it is attempted to modulate and facilitate the cure of a wound. The use of PRP is based on the theoretical premise that by concentrating platelets the effects of the growth factors (PDGF, TGF-beta, IGF-I and -II) so released will be increased. Marx's original technique is described above all. This prescribes the sampling of a unit of blood (450-500 ml) and the use of a cell separator. We then analysed the technique of Marx and Hannon in which the quantity of blood sampled is reduced to 150 ml, and the two simplified techniques of the Sacchi and Bellanda group. Finally, a new PRP extraction technique is described. We conclude that platelet gel allows access to autologous growth factors which by definition are neither toxic nor immunogenic and are capable of accelerating the normal processes of bone regeneration. PRP can thus be considered a useful instrument for increasing the quality and final quantity of regenerated bone in oral and maxillo-facial surgery operations.     

Growth factors in periodontal regeneration

Abstract:  Inflammatory periodontal disease is an almost ubiquitous disorder in the adult population. Cases or sites with moderate to advanced disease often continue to show signs of inflammation after non-surgical approach. Our current understanding of periodontal healing is based on a hypothesis by Melcher who proposed that the cell type that repopulates the exposed root surface at the periodontal repair site will define the nature of the attachment/repair that take place. If mesenchymal cells from periodontal ligament/perivascular region of the bone proliferate and colonize the root surface, regeneration occurs. Growth factors are natural cell products that are released or activated when cell division is needed. This action typically occurs during such events as wound healing or tissue regeneration. Activated platelets at the wound margins release several growth factors such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-α, epidermal growth factor etc. Cells adjacent to the injured site also are induced to release growth factors such as insulin-like growth factor-I, PDGF, TGF-α and TGF-α within a few hours after injury. In periodontal regeneration, the coronal re-establishment of the periodontal ligament (PDL) is required together with corresponding cementum and supporting alveolar bone. Thus, agents which promote periodontal ligament fibroblast (PLF) proliferation and migration as well as collagen biosynthesis would appear to be mediators for enhancing new PDL formation. When combinations or cocktails of different factors are used, greater repair is achieved than when individual factors are applied.     

Evaluation of platelet-rich plasma in combination with freeze-dried bone in the rabbit cranium. A pilot study

Platelet-rich plasma (PRP) offers a new and potentially useful adjunct to allograft materials in oral and maxillofacial bone and implant reconstructive surgery. This study compares bone healing in four cranial defects in the rabbit grafted with freeze-dried mineralized bone (FMB) alone, FMB+PRP, freeze-dried demineralized bone (FDDB) alone, and FDDB+PRP. Fifteen New Zealand white rabbits were included in this randomized, blind, prospective pilot study. Four equal 8 mm diameter defects were created in each rabbit cranium and immediately grafted with the above materials. Five rabbits were evaluated at 1, 2, and 4 months. Radiographically, FMB+PRP showed a tendency toward increased bone density over FMB alone, but was not statistically significant (P>0.05), and FDDB+PRP showed a tendency toward increased bone density over FDDB alone, but was not statistically significant (P>0.05). Histomorphometrically, FMB+PRP showed a tendency toward increased bone area over FMB alone at 1 and 4 months, but was not statistically significant (P>0.05), and FDDB+PRP showed a tendency toward increased bone area over FDDB alone, at 1 and 2 months, but was not statistically significant (P>0.05). This study failed to show a radiographic or histomorphometric increase in bone formation with the addition of PRP to either FMB or FDDB in non-critical-sized defects in the rabbit cranium.