Socket Preservation Technique Research Articles

Socket-shield Technique and immediate implant placement for ridge preservation in the aesthetic region: a 1-year clinical and tomographic follow-up

Objective: To describe the clinical, radiographic and tomographic aspects, as well as complications, success, aesthetic and functional results of an implant placed using the “socket shield” technique. Case Details: Represents a 46-year-old patient, with increased mobility of the crown in the bucco-palatal direction, with indication for extraction replaced by immediate implant. Atraumatic extraction, socket preservation technique and immediate implant placement were performed. The socket-shield technique was designed for placing implants to protect the oral bone and achieve adequate aesthetics. The buccal fragment of the tooth was kept fixed and the implant was placed in contact with the tooth fragment. Cone Bean computed tomography showed bone formation in the buccal aspect 1 year later, and demonstrated stability of the peri-implant bone tissue and replacement of the root remnant by bone. The clinical appearance demonstrated maintenance of peri-implant soft tissues and good aesthetics without gingival retraction. Final considerations: One-year follow-up shows adequate healing and healthy peri-implant tissue, suggesting that the socket-shield technique with immediate implant placement can be an excellent alternative for preserving the vestibular cortex and implant placement, especially in the aesthetic area.

Cone-Beam Computed Tomography and Histological Findings for Socket Preservation Techniques Using Different Grafting Materials: A Systematic Review

Socket preservation techniques have been used to maintain the ridge dimension following tooth extraction. The materials used influence the quality and quantity of newly formed bone. Therefore, the aim of this article was to systematically review the literature reporting both histological and radiographic outcomes of socket preservation techniques after tooth extraction in human subjects. A systematic electronic search was performed in the electronic databases. English language clinical studies that were published between 2017 and 2022 and included both histological and radiographic findings for the test and control groups. Our primary search produced 848 articles, and of these, 215 were duplicate studies. A total of 72 articles were then eligible for full-text reading. The review included eight studies that met its inclusion criteria. Three outcomes were compared in the included studies. The percentage of newly formed bone ranged from 21.34 ± 9.14% to more than 50% of new bone formation. The materials that showed more than 50% of newly formed bone formation were demineralized dentin graft, platelet-rich fibrin, freeze-dried bone allograft, corticocancellous porcine, and autogenous bone. Four Studies did not report the percentage of the residual graft materials, while those who reported showed a variable range of a minimum 1.5% to more than 25%. One study did not report the changes in horizontal width at the follow-up period, while other studies ranged from 0.6 mm to 10 mm. Socket preservation represents an efficient technique to preserve the ridge contour with satisfactory newly formed bone in the augmented site and maintaining the vertical and horizontal dimensions of the ridge.

Healing of particulate allografts mixed with platelet concentrates in ridge preservation and sinus lift: a prospective histomorphometric study

The objective of the present study was to evaluate the bone quality of sinus and alveolar grafts following filling with particulate allogenous bone (DFDBA 300-500μm) and platelet concentrate (platelet-rich fibrin, PRF). A prospective interventional clinical study was carried out. A total of 40 bone cores, 2mm in diameter, were taken from 21 patients: 22 from grafted alveoli, 7 from grafted sinus sites, and 11 from native bone used as a control. Fixed, paraffin-embedded samples were subjected to histological staining with hematoxylin-eosin and Masson's trichrome. Bone maturity of the samples was evaluated by two independent operators using histomorphometric analysis. There existed a greater proportion of lamellar neoformed bone than woven neoformed bone as the healing time increased. Moreover, there was also an increasing proportion of newly formed bone in the grafted sockets as a function of healing time (average: 41.22%≤5 months, 55.89%˃5 months). Resorption of DFDBA particles also appears to be correlated with healing time in the grafted socket (average: 15.43≤5 months, 13.72%˃5 months). In conclusion, performing sinus lift and alveolar socket preservation techniques using DFDBA and PRF results in high quality, mature bone tissue according to histological criteria.

Different extra-coronal restoration options of hemisected teeth on structurally compromised mandibular molar: Report of two cases

Structurally compromised teeth tend to be extracted due to its their poor prognosis, however, hemisection may serve as an alternative option in selected cases. This case report is aimed to discuss two cases of hemisected mandibular molars with two different approaches for post-hemisection restoration. Case 1 presents with terminal tooth 37 diagnosed with a cracked tooth involving severe bone loss on the mesial root. The tooth was hemisected and restored with a mesially cantilevered full ceramic crown. Case 2 presents with root caries on an endodontically treated tooth 46 on a patient with bruxism, with an inadequate ferrule on the distal segment. The tooth was hemisected utilizing the socket preservation technique, and the tooth was restored with a conventional fixed-fixed bridge with a second abutment on tooth 47.

Techniques for Extraction Socket Regeneration for Alveolar Ridge Preservation

Alveolar bone undergoes volumetric changes after extraction due to physiologic bone remodeling. The amount of alveolar bone available during prosthodontic treatment can affect the esthetic outcome of the treatment and make implant placement challenging. Socket preservation techniques are advocated postextraction to maintain the bone's vertical and horizontal alveolar bone dimensions and prevent its atrophy. This review is oriented toward a clinician, describing the different materials and techniques in practice today for socket preservation. A variety of methods have been studied as a means to stop alveolar ridge resorption. While immediate implant placement was recommended as a socket preservation technique, clinical trials have not demonstrated favorable results. The main techniques favored by clinicians today involve bone grafts, bone substitutes, barrier membranes, and combinations thereof. As with periodontal defects, these materials show favorable outcomes in alveolar bone regeneration and ridge preservation. Tooth bone grafts, both autogenous and allogenous, have been recommended recently for ridge preservation as they are chemically similar to bone and can induce osteogenesis. The use of autologous platelet concentrates has yielded contradictory results in studies. Cutting-edge approaches entail using growth factors and tissue engineering concepts. While these strategies are still in the development stages, it has peerless potential in preserving and regenerating alveolar bone. Alveolar ridge resorption is an unavoidable physiological process after extraction and leads to severe bone deficiencies, affecting esthetics. These changes in alveolar ridge dimensions make implant placement difficult and affect the longevity of the implant. Clinical intervention can prevent alveolar bone resorption and preserve the ridge. Bone grafts and substitutes including concentrates remain the best choices in ride preservation. The use of growth factors and tissue engineering concepts requires further clinical trials before widespread use in clinical practice.

Socket Preservation Using Bovine Bone Graft and Pericardium Membrane: A Case Report

Background: Tooth extraction is followed by a resorption of the bone in the buccal or facial portion, up to 50% in the first six months after the extraction. Bone loss mainly results from damage to the periodontal bone ligament complex. Socket preservation is a surgical procedure aimed to maintain an alveolar ridge after extraction, eliminating or minimizing the need for future augmentation in implant-prosthetic rehabilitation. Socket preservation techniques use some regenerative material such as bone graft and membrane.
 Objective: To discuss socket preservation procedures using bovine bone graft and pericardium membrane.
 Method: A 48-year-old woman presented to the Dental and Oral Hospital of Hasanuddin University to have tooth 47, which was mobile and extruded, extracted. Patient had no systemic disease and did not use any drugs. Clinical and radiograph examinations showed bone resorption in the surrounding edentulous area. The patient wanted to wear prosthesis but the bone resorption showed that socket preservation was needed to maintain the alveolar ridge high. The case was diagnosed as chronic periodontitis. Atraumatic extraction was done and bovine bone graft was placed in the socket, followed by the placement of pericardium membrane. Soft tissue healing was clinically evaluated.
 Results: Control period after one week showed apparent uneventful clinical healing in the socket. Patient was satisfied with the treatment.
 Conclusion: The socket preservation procedure is an effective treatment for maintaining the alveolar ridge high from excessive resorption, especially for prosthesis treatment.
 Keywords: alveolar ridge, bone bovine, pericardium membrane, socket preservation

Socket preservation techniques: An overview with literature review

Background: Alveolar bone undergoes residual ridge resorption after tooth extraction and eventually results in inadequate soft tissue and alveolus for dental implant rehabilitation. Therefore, to overcome this, socket preservation is performed immediately after tooth extraction to maximize bone formation within the socket. Aim: This review is aimed to give a brief overview of rationale, indications, surgical techniques, decision tree, and recent literature evidence regarding different techniques of socket preservation. Methods: An electronic search was performed in databases such as PubMed, Scopus, and Google Scholar with the key words socket preservation, particulate bone grafts, membranes, and platelet-rich fibrin. The articles published from August 2008 to February 2022 were included for the search. Results: A total of 18 articles were considered for the review which included 8 meta-analysis, 7 systematic review, and 3 randomized control trial. The outcome parameters such as clinical, radiographical, and histomorphometrical ridge dimensions were analyzed. Conclusion: Socket preservation is one of the effective treatment options to prevent bone resorption following an atraumatic extraction with the use of appropriate biomaterials and membranes. The reliability and power of evidence is strong for the combined technique of using bone graft and membrane.

Double Layer Socket Preservation Technique Associated with Xenogenous Bone Graft and Polypropylene Membrane: A Case Report

With the demand for tooth/gum aesthetics in implant-supported rehabilitations, the surgeon, whether an implant specialist or not, increasingly needs to be mindful of proper care for socket preservation following extraction. The paper presented here reports the case of a male patient who manifested dental impairment of the Upper Left First Molar (tooth #26) (in FDI notation); following tomographic analysis and after reaching a consensus with the patient, the decision was made to extract said tooth and preserve the socket for subsequent implant placement. The aim of the case report is to present a clinical case of alveolar ridge preservation through the “Double Layer Socket Preservation” technique, a technique created by Barry Barthee, whereby a xenogenous graft under an xenogenous type III collagen membrane was combined with a polypropylene barrier. Following research and study results on the subject, it was concluded that by applying this technique, the alveolar ridge is greatly preserved and bone volume is maintained, both of which are very important factors for good health of the tissues surrounding the implant and consequent increase in the survival of the implant itself.

Double Layer Socket Preservation Technique Associated with Xenogenous Bone Graft and Polypropylene Membrane: A Case Report

With the demand for tooth/gum aesthetics in implant-supported rehabilitations, the surgeon, whether an implant specialist or not, increasingly needs to be mindful of proper care for socket preservation following extraction. The paper presented here reports the case of a male patient who manifested dental impairment of the Upper Left First Molar (tooth #26) [in FDI notation]; following tomographic analysis and after reaching a consensus with the patient, the decision was made to extract said tooth and preserve the socket for subsequent implant placement. The aim of the case report is to present a clinical case of alveolar ridge preservation through the “Double Layer Socket Preservation” technique, a technique created by Barry Barthee, whereby a xenogenous graft under an xenogenous type III collagen membrane was combined with a polypropylene barrier. Following research and study results on the subject, it was concluded that by applying this technique, the alveolar ridge is greatly preserved and bone volume is maintained, both of which are very important factors for good health of the tissues surrounding the implant and consequent increase in the survival of the implant itself.

Diente autógeno de extracción inmediata como material de injerto para la conservación de alvéolos frescos: Una revisión sistemática.

Objectives: To evaluate the use of extracted autogenous teeth for socket preservation after tooth extraction. Material and Methods: Cochrane, Scopus, and PubMed databases search was conducted to identify human clinical studies reporting the clinical, radiographic and/or histological outcomes of socket preservation techniques with autogenous extracted tooth Only studies published in English language in the last 10 years were included in the study. Results: In total, 82 articles were identified. Five articles were included in the review. They included 58 teeth that were prepared as a graft for socket preservation. The grafts derived from autogenous teeth were presented in three forms: particles, blocks and powder. The mean bone loss ranged from 0.28 mm to 0.41mm in height and 0.15 mm in width.Conclusion: Immediate autogenous extracted tooth as a grafting material for fresh socket preservation is promising for future daily clinical practice. More clinical comparative studies are needed.

A 15-year unique observational study of intraligamentary local anaesthesia for posterior mandibular extractions.

Introduction Intraligamentary local anaesthesia (ILA) with articaine is described as an effective alternative to inferior alveolar nerve block (IANB) for extraction of posterior teeth in the mandible, with reduced risk of complications.Aim To investigate ILA with 4% articaine and conventional syringe as a unique method for providing tooth extractions in the posterior mandible.Materials and methods All consecutive teeth to be extracted in the posterior mandible were recruited to the study, within exclusion criteria, between 2002 and 2017 in one London NHS and private dental practice. Four percent articaine was given by ILA with a conventional syringe slowly at two points lingual and two points buccal adjacent to each tooth. Extraction procedures were all performed flapless. Heavily broken-down teeth (n = 43) were extracted by sectioning of roots, guttering and elevation with luxators using socket preservation techniques. Demographic, quantitative and qualitative data were collected at initial appointments and up to 15 years at review.Results The median age was 64 years (interquartile range 17). Teeth extracted included 272 mandibular molars and second premolars, due to periodontal disease (34%), irreversible pulpitis (29%) or posterior tooth fracture (27%). The majority of extractions were second molars (44%), followed by first molars (29%), second premolars (17%) and third molars (10%). Sufficient anaesthesia was achieved within five minutes for all extractions. Procedures lasted less than 30 minutes. Patient feedback reported that the extraction using ILA was quicker than expected and painless, with limited anaesthesia of tissues other than the teeth to be extracted. Numeric rating scale (NRS) scores for pain (0-10) were all less than 3. No complications were recorded.Conclusion The ILA anaesthetic technique is effective for the purpose of a broad range of posterior tooth extractions in the mandible and within certain clinical parameters. It mitigates risks, including nerve injury and cardiovascular disturbances, associated with repeated IANB. This is the largest study of its kind and is conducted in primary care.

Hemisection with socket preservation using Platelet Rich Fibrin [PRF] - A case report with one year follow up

With advances in dentistry as well as the increased patients' desire to retain their natural teeth, there is a paradigm shift from extraction to the preservation of teeth. Mandibular first molars are the primary occlusal load-bearing teeth, commonly extracted teeth due to dental caries and periodontal disease. Hemisection is a conservative alternative to retain a hopeless tooth. Following endodontic treatment and selective root removal, the remaining portion of the tooth is splinted to the adjacent teeth with a fixed partial denture prosthesis. The resorption of the alveolar ridge surrounding the extraction socket may complicate the subsequent prosthetic procedure. Hence, socket preservation technique evolved, which prevents such untoward changes in the extraction socket. This case report shows hemisection procedure in a grossly carious first mandibular right molar with furcation involvement of a healthy 40-year-old female patient followed by autologous platelet-rich fibrin placement in the extraction socket. One year follow-up showed little alveolar resorptive changes with better healing and function clinically.

Impact of Socket Preservation Technique Using Autogenous Dentin Graft and Hydroxyapatite Crystals on Primary Stability of Dental Implants in Same Individuals: A Pilot Study

A pilot study was conducted to analyze and compare the stability of dental implants using 2 different graft materials (autologous dentin graft and an alloplastic hydroxyapatite [HA] crystal) in the same patient. As far as we know, this study is first of its kind where socket preservation has been done using 2 different grafts in the same patient. Ten patients undergoing extraction of at least 2 teeth were selected. Atraumatic extractions were performed. Out of the 2 extraction sockets, 1 was grafted with autogenous tooth graft and other with HA crystals. Computed tomography scan was performed 3 months after grafting to evaluate bone mineral density. Primary implant stability was measured using resonance frequency analysis. It was observed that among both sites, autogenous tooth grafted sites showed better results.

Microbiological and FE-SEM Assessment of d-PTFE Membrane Exposed to Oral Environment after Alveolar Socket Preservation Managed with Granular nc-HA

The aim of this study was to analyze, by the aid of microbiological analysis and the field emission scanning electron microscopical (FE-SEM) analysis, the role of high-density polytetrafluoroethylene (d-PTFE) membranes in avoiding the microbial colonization of a nanocrystalline hydroxyapatite (nc-HA) bone graft and the involvement of this colonization in the healing process. Six patients underwent extraction of unrecoverable teeth, and a socket preservation technique was carried out with nc-HA synthetic bone graft and then covered with a d-PTFE membrane. After 28 days from surgery, FE-SEM analysis and BioTimer assay technique to assess the microbiological count of streptococci species were carried out. Data were collected and analyzed by the Student's t test (confidence interval: 95%). The mean amount of bacteria measured on the upper side of the membrane was 6.52 ± 0.50 CFU, while on the lower side, it was 6.59 ± 0.40 CFU. Significant differences were not found between the two sides of the membrane or between the different sectors (p > 0.05). The FE-SEM analysis revealed structured biofilms on both sides of the membrane: species of cocci, bacilli, and fusobacteria were recognizable in occasional settled vegetations. Since the amount of bacteria found was low, the improved impermeability of the d-PTFE membrane permitted the healing process to proceed uneventful and without signs of infection or inflammation. The infection of the graft site could lead to a failure of the socket preservation technique which could delay or compromise the rehabilitation following procedures. The use of d-PTFE can improve the bone regeneration thanks to its antimicrobial properties.

Application of the technique of preserving the volume of the alveolar bone by using a fragment of the extracted tooth to cover the alveola in comparison with the alveolas of the extracted teeth healing under the blood clot

Удаление зуба неизбежно влечет за собой процессы перестройки альвеолярного гребня и уменьшение объема его твердых и мягких тканей. Цель — определение эффективности сохранения объема мягких тканей после удаления зуба при использовании методики сохранения фрагмента корня удаленного зуба. Материалы и методы. У пациентов двух групп измеряли толщину вестибулярной слизистой оболочки в проекции зенита коронки до удаления зуба и спустя 6 месяцев после фиксации постоянной реставрации. Также исследовали структурные особенности мягких тканей в области фрагмента корня удаленного зуба. Через 3 месяца заживления фрагмент корня удаляли, проводили забор мягких тканей, располагающихся под ним, с дальнейшим проведением гистоморфологического исследования. Результаты. В контрольной группе (20 человек) средняя толщина вестибулярной слизистой оболочки в проекции зенита коронки до удаления зуба составила 1,44 мм, после удаления зуба заживление лунки происходило классически, под сгустком крови. В исследуемой группе (20 пациентов) средняя толщина слизистой оболочки составила 1,52 мм, после удаления зуба использовалась техника презервации лунки с помощью фрагмента корня удаленного зуба. Через 6 месяцев после установки постоянной коронки средняя толщина слизистой оболочки в проекции зенита у пациентов I группы составила 0,89 мм, у пациентов II группы — 1,5 мм. По результатам гистоморфологического исследования мягкие ткани, находящиеся под фрагментом удаленного зуба после заживления лунки, представляют собой незрелую соединительную ткань с некоторым количеством пролиферирующих клеточных элементов и не являются патологическими. Выводы. Использование фрагментов удаленных зубов для закрытия лунки после удаления зуба позволяет сохранить больший вестибулярный объем мягких тканей, чем при заживлении лунки классическим образом, под сгустком крови. Использование фрагментов удаленных зубов для закрытия лунки удаленного зуба позволяет сохранить достаточный вестибулярный объем мягких тканей, что является преимуществом для дальнейшего имплантологического лечения.

Modified Procedure in a Socket-Shield technique in the aesthetic zone - Case report

Purposes: After tooth extraction alveolar socket bone undergoes a remodelling process. The horizontal and the vertical bone losses complicate dental rehabilitation with implants. Socket-Shield technique maintain the periodontal attachment including cementum, periodontal ligament and bundle bone. In this report this technique was indicated to replace the lost teeth. Case report: A socket shield technique was used for immediate implant placement on a non-restorable teeth by failure of crowns in teeth 12, 11 and 21. Through a osteotomy and manipulation of soft tissues with provisionals it was possible to correct the gingival contours and zeniths. Conclusions: Atraumatic extraction and socket preservation technique decreases the alveolar bone resorption by maintaining the hard and the soft tissue volume. Provisionalization allows management of the soft tissues around the implants. This treatment offers a predictable aesthetic and functional result .

Extraction Socket Preservation Using Growth Factors and Stem Cells: a Systematic Review

ABSTRACTObjectivesTo evaluate the reported literature on the use of stem cells or growth factors for post extraction treatment of the alveolar bone.Material and MethodsA NCBI PubMed and PubMed Central databases search was conducted between September 2010 and August 2018, to identify animal or clinical studies reporting the clinical, radiographical and/or histological outcomes of socket preservation techniques after applying mesenchymal stem cells or growth factors. Only studies published in English language in the last 10 years were included in the study.ResultsEleven studies were identified fulfilling the inclusion criteria. They evaluate a total of 386 post extraction sockets. The main tested materials identified in the current review were bone morphogenetic protein-2 - 3 studies and mesenchymal stem cells - 3 studies. Other comparators were bone morphogenetic protein-9, platelet-derived growth factor-BB homodimers and bone marrow. Overall evaluation indicate positive results for all test groups showing differences in final socket width between 0.64 and 1.28 mm favouring the test groups. Histologically, no particular differences are detected between test and control groups. Most of the studies present low risk of bias.ConclusionsIn general, the use of mesenchymal stem cells or bioactive osteogenic molecules favours bone regeneration after tooth extraction, as evaluated clinically, radiographically and histologically. However, specific differences that support particular recommendations are still unclear in light of the current published evidence. Future studies should include the standardization of the mesenchymal stem cells selection and purification as well as dosage and delivery methods of bioactive molecules.

Section Plane Effects on Morphometric Values of Microcomputed Tomography.

Objectives Histomorphometry is the established gold standard for inspection of trabecular microstructures in biomaterial research. However, microcomputed tomography can provide images from the perspective of various section planes. The aim of the present study was to evaluate the effects of different section planes, which may cause bias in two-dimensional morphometry, on the morphometric values of microcomputed tomography. Methods A socket preservation technique was performed on the extracted premolar area of 4 beagle dogs. After an 8-week healing period, a total of 16 specimens were obtained and analyzed with conventional histomorphometry and microtomographic morphometry. Using the original images of the histologic specimens for comparison, the most similar tomographic image was selected by trial and error. Then, the section plane was then moved with ±79 μm parallel offsets and rotated ±10° around the center from the occlusal view. The images were compared in terms of bone, graft, and noncalcified area, and the concordance correlation coefficient (CCC) was calculated. Results There was a high CCC in the comparison between histomorphometric images and the most similar microtomographic images. However, the CCC value was low in the comparisons with both parallel movement and rotation. Our results demonstrate that the sectioning plane has a significant effect on measurements. Conclusion Two-dimensional morphometric values for biomaterial research should be interpreted with caution, and the simultaneous use of complementary 3-dimensional tools is recommended.

New technique for alveolar preservation – the anodized titanium foil concept

Background The socket preservation techniques are used to minimize bone loss and maintain gingival tissues volume after tooth extraction. However, the volume preservation rate of the alveolar process is not predictable, and most of the guided bone regeneration techniques change the mucogingival line by coronally positioning the flap to cover a membrane, what may impair implant aesthetics and function. Aim/Hypothesis The aim of this clinical prospective study was to evaluate a new alveolar preservation technique using an anodized titanium membrane (ATM), which remain exposed to the oral cavity, analyzing tomographical bone measurements pre-surgically and 6 months after surgery. Material and Methods Eighteen healthy patients having one hopeless tooth were selected to receive the new socket preservation technique. The teeth were carefully extracted, then a small flap was raised to allow the ATM insertion. The alveolus was filled with anorganic bovine bone graft and the ATM was trimmed and adapted over the crestal bone and below the gingival margin. Nylon sutures were used to hold the ATM in position. Proper post-operatory medications were prescribed (Amoxicylin 500 mg, Ibuprofen 200 mg and PerioGard rinse). Fifteen days after surgery the ATMs were removed with pliers. The measurements of the alveolus thickness were recorded in the baseline and 6 months after the surgeries, using cone beam tomographies, evaluating the distance between buccal and palatal bone plates, and were performed in the center of the alveolus, 1 mm above the palatal crestal bone. The data was statistically analyzed by Student´s t-test (P < 0.05 was considered). Results The results are presented in percentage, to minimize the influence of the different alveolus sizes. After 6 months, the mean volume maintenance was 97.66% (P = 0.07) for all the 18 patients. In cases with vestibular bone plate loss (7 patients), the average of volume maintenance was 112.89%, with some volume gain (P = 0.07). When there was no vestibular bone plate loss (11 cases) the result was 87.97% (P = 0.002). Evaluation the type of teeth, for molar teeth (7 cases), mean volume maintenance was 89.55% (P = 0.014), and for no molar teeth (11 cases), the average of volume maintenance was 102.82% (P = 0.46). Conclusions and Clinical Implications The use of ATM in this prospective case series presented superior tomographic results for tissue volume maintenance after 6 months, when compared to the scientific literature addressing GBR procedures using collagen membranes and connective tissue grafts. Future randomized controlled clinical studies are suggested to investigate the regenerative potential of this new alveolar preservation technique.

Comparison of buccal bone plate resorption between different extraction socket preservation techniques‐ use of allograft, xenograft and PRGF

Comparison of buccal bone plate resorption between different extraction socket preservation techniques‐ use of allograft, xenograft and PRGF