A new animal model for molecular biological analysis of the implant-tissue interface: spatial expression of type XII collagen mRNA around a titanium oral implant

The objective of this study was to develop an animal model to investigate the molecular biological healing events at the tissue-implant surface occurring in the alveolar bone. Newly designed mini-titanium implants (2mm in length and 1 mm in diameter) were placed in the maxilla of retired-breeder male Sprague-Dawley rats. The implants were placed in freshly drilled holes in the maxillary bone, or in an area close to the roots of the maxillary first molar. The healing phase in each group was studied histologically at 28 days and at 56 days by means of non-decalcified polymethylmethacrylate-embedded sections and decalcified paraffin-embedded sections. Initial osseointegration was observed at 28 days, with mature osseointegration seen at 56 days. Specimens with implants placed immediately adjacent to the root showed fibrous healing at the implant-tissue surface. As a pilot study, the expression of type XII collagen, a molecular marker specific to the mature periodontal ligament (PDL), was studied by in situ hybridization. There was an absence of type XII expression close to the implant surface, whereas there was a zone of type XII collagen expression closest to the bony wall. Our preliminary results indicated a significant molecular variation in the fibrous-implant interface. This model will be useful in studies of the wound-healing patterns of the extracellular matrix around oral implants specifically relevant to alveolar bone osseointegration and potential formation of PDL.     

Ligature-induced marginal inflammation around osseointegrated implants and ankylosed teeth: stereologic and histologic observations in cynomolgus monkeys (Macaca fascicularis)

The aim of the investigation was to provide quantitative and qualitative histologic data on marginal inflammation around osseointegrated implants. The significance of the lack of a periodontal ligament in the initial breakdown phase of supporting tissues in implants was examined by comparing stereologic and histologic manifestations of ligature-induced marginal inflammation around osseointegrated implants with those around ankylosed and normal control teeth in 8 cynomolgus monkeys (Macaca fascicularis). Clinical and radiographic findings have been reported elsewhere. The marginal connective tissue around ligated implants was infiltrated by a significantly increased total number of lymphocytes, plasma cells, and neutrophils compared to non-ligated implants and teeth. The total number of lymphocytes around ligated implants was significantly higher than around ligated ankylosed and normal control teeth. There were, however, no significant differences in the total number of plasma cells and neutrophils within the ligated group. Osteoclasts were exclusively observed around ligated implants and ankylosed teeth. Although variations in microbiota and susceptibility of different jaw positions to periodontal break-down may influence the results of the present study, the results seem to substantiate the theory that marginal inflammation around implants and ankylosed teeth may have more serious implications than does marginal inflammation around teeth with a periodontal ligament. Since presence of osteoclasts was not related to the absence of cervical cementum with inserting gingival fibers around ligated ankylosed teeth, the increased susceptibility of bone loss of implants is probably not caused by the absence of these tissue components. In contrast, the histologic observations seem to support that the increased susceptibility for bone loss around implants may be related to the absence of a periodontal ligament.     

Experimental peri-implantitis in consecutively placed, loaded root-form and plate-form implants in adult Macaca mulatta monkeys

This study is part of an on-going project describing the character of round- and plate-form implants placed in a primate model. In this paper 20 loaded plate-form and 23 root-form implants were connected to prostheses and experimental peri-implantitis was induced by ceasing scaling procedures and placing braided silk ligature around the implants. Twenty-four prostheses utilizing natural teeth were studied for comparison. Clinical measurements were carried out monthly for 6 months and radiographic measurements at 3 and 6 months post-ligature placement and cessation of scaling. Both root-form implants and plate-form implants showed a significant loss of crestal bone height at 3 and 6 months after ligature placement (P < .001 after 6 months). The difference in bone loss between plate- and root-form implants, however, was not significant.     

Parental awareness of dental caries in toddlers

Endodontic endosseous implants stabilize teeth that have crown-root ratios compromised by periodontal disease, trauma, or apical resorption. By increasing the crown-root ratio, the implant improves the prognosis of the tooth, thus increasing its longevity. The purpose of this study was to evaluate, in vivo, the healing response to a newly introduced titanium endodontic implant. Eight implants were placed in the maxillary incisors and mandibular premolars of two adult beagle dogs after completion of root canal and osseous preparation. Peri-implant tissues were examined radiographically and histologically at 6 months postinsertion. Radiographically, the periapical area and tissue surrounding the implants seemed normal. Histologically, fibrous connective tissue and healthy bone intimately surrounded the implant. Epithelium or chronic inflammatory cells were not observed along the length of the implant. These findings suggest that titanium is a biocompatible metal when used as an endodontic endosseous implant.     

Effects of guided bone regeneration around commercially pure titanium and hydroxyapatite-coated dental implants. II. Histologic analysis

The purpose of this study was to determine which treatment of a large osseous defect adjacent to an endosseous dental implant would produce the greatest regeneration of bone and degree of osseointegration: barrier membrane therapy plus demineralized freeze-dried bone allograft (DFDBA), membrane therapy alone, or no treatment. The current study histologically assessed changes in bone within the healed peri-implant osseous defect. In a split-mouth design, 6 implants were placed in edentulous mandibular ridges of 10 mongrel dogs after preparation of 6 cylindrical mid-crestal defects, 5 mm in depth, and 9.525 mm in diameter. An implant site was then prepared in the center of each defect to a depth of 5 mm beyond the apical extent of the defect. One mandibular quadrant received three commercially pure titanium (Ti) screw implants (3.75 x 10 mm), while the contralateral side received three hydroxyapatite (HA) coated root-form implants (3.3 x 10 mm). Consequently, the coronal 5 mm of each implant was surrounded by a circumferential defect approximately 3 mm wide and 5 mm deep. The three dental implants in each quadrant received either DFDBA (canine source) and an expanded polytetrafluoroethylene membrane (ePTFE), ePTFE membrane alone, or no treatment which served as the control. Clinically, the greatest increase in ridge height and width was seen with DFDBA/ePTFE. Histologically, statistically significant differences in defect osseointegration were seen between treatment groups (P < 0.0001: DFDBA/ePTFE > ePTFE alone > control). HA-coated implants had significantly greater osseointegration within the defect than Ti implants (P < 0.0001). Average trabeculation of newly formed bone in the defect after healing was significantly greater for HA-coated implants than for titanium (P < 0.0001), while the effect on trabeculation between treatments was not significantly different (P = 0.14). Finally, there were significantly less residual allograft particles in defect areas adjacent to HA-coated implants than Ti implants (P = 0.0355). The use of HA-coated implants in large size defects with DFDBA and ePTFE membranes produced significantly more osseointegration histologically than other treatment options and more than Ti implants with the same treatment combinations. The results of this study indicate that, although the implants appeared osseointegrated clinically after 4 months of healing, histologic data suggest that selection of both the implant type and the treatment modality is important in obtaining optimum osseointegration in large size defects.     

A comparative study of osseointegration of titanium implants in autogenous and freeze-dried bone grafts

PURPOSE: This study was undertaken to compare the rate and degree of osseointegration of dental implants when placed into either autogenous corticocancellous chip or freeze-dried corticocancellous chip bone grafts. MATERIALS AND METHODS: The canine ilium was used as the model site. Thirty experimental and 15 control implants were placed in 15 dogs: autogenous versus freeze-dried corticocancellous chip bone grafts around the exposed implant surfaces. In addition to the placement of control implants, the apical portion of the grafted implants acted as their own control. The implants were harvested at 1, 2, and 3 months. The evaluation of the integration process was performed by means of light microscopy, microradiography, and histomorphometry. RESULTS: Using this model, the results indicate that at 1 month there was no statistical difference in the degree of osseointegration in the two bone grafts. At 2 months, there was a statistically greater degree of osseointegration noted in the autogenous corticocancellous chip sites than in the freeze-dried bone grafts. At 3 months, the degree of osseointegration in the two groups was 70% and 33%, respectively. At 3 months, there was virtually 100% integration with trabecular bone at the control implant sites. CONCLUSION: The results indicate that at 2 months postoperatively implants placed in an autogenous bone chip graft osseointegrate to a significantly greater degree than implants placed in a freeze-dried bone chip graft, and this difference remains at 3 months.     

Effects of partial ventriculectomy on left ventricular mechanical properties, shape, and geometry in patients with dilated cardiomyopathy

This study evaluated the 6-month clinical response to sustained-release tetracycline fibers used alone or with scaling and root planing in 25 adult periodontal maintenance patients. All subjects had at least one pocket > or = 4.0 mm that bled on probing and required therapy. Thirty-six teeth were treated with tetracycline fibers for 7 to 12 days; twelve of the 36 teeth also received scaling and root planing. The selection of teeth for scaling and root planing was based on the condition of the teeth. Therapeutic results were evaluated by changes in probing depth and frequency of bleeding on probing. Use of tetracycline fibers and fibers with scaling produced 1.8- and 1.7-mm reductions in probing depth, respectively, 1 month after treatment; reductions declined to 1.3 and 0.8 mm at 3 months, but rebounded to 1.5 and 1.3 mm at 6 months. The percentage of teeth exhibiting bleeding on probing decreased from 100% at baseline to 68% and 50% in the fiber and fiber plus scaling groups, respectively, at 6 months. None of the differences was statistically significant. Tetracycline fibers clearly decreased clinical signs of periodontal inflammation. Addition of scaling and root planing at the time of fiber placement further decreased, although not significantly, the degree of inflammation.     

Schizophrenia in twins

Attempts to save natural teeth have created numerous restorative, endodontic, and periodontal techniques it has always been considered the treatment of choice to save teeth whenever possible, and extreme efforts to save teeth are often considered because of the poor treatment alternatives for replacing them. Today osseointegration provides a predictable means of replacing teeth; therefore, retaining questionable teeth may not be as necessary as in the past. This article reviews situations in which the selective extraction of compromised natural teeth or even healthy natural teeth is considered because of alternative treatment options utilizing osseointegrated implants.     

Biomechanical considerations when combining tooth-supported and implant-supported prostheses

The force distribution of multiple tooth-supported and implant-supported prostheses is completely different. A direct correlation exists between the degree of flexion at the site of loading and the amount of force distribution to other members of the prosthesis. Micromovement produced by the periodontal fibers facilitates force distribution to all the root surfaces of the natural tooth abutments. The rigidity of the implant/abutment/prosthesis configuration concentrates the force at the crestal bone at the site of loading with limited distribution to the remaining implants. Differential mobility concentrates the force distribution to the bone support of the most rigid members of splinted natural teeth or to the implants when they are united with natural teeth in a combined prosthesis. Implants always support the natural teeth and never the other way around. Therefore a nonrigid attachment is recommended between a tooth-supported prosthesis and an implant-supported prosthesis when they are combined. However, when implants are interspersed with natural teeth in the same prosthesis, the restoration will be implant borne. This requires special force distribution analysis to prevent implant overload.     

Differential expression of the keratinocyte growth factor (KGF) and KGF receptor genes in human vascular smooth muscle cells and arteries

The objective of this study was to analyze the efficacy and correlation between clinical and histologic parameters used to evaluate oral implants. After extraction of the premolars and a healing time of 4 months in 16 Dutch goats, four Br?nemark implants were placed in the maxillary left and right premolar regions. After a healing time of 6 months, followed by another 4 months with the permucosal abutments, the goats were sacrificed and the jaws were block-resected. Before histologic preparation, long-cone radiographs were made and Periotest scores of the implants were recorded. Bone level measured histomorphometrically were found to be 0.85 mm more apically, compared to that measured radiologically (P = .001). Furthermore, statistically significant correlations (P > 0.2) were not found between the Periotest values of the calcium-phosphate-coated and uncoated implants for (1) the first thread in contact with bone, or (2) with the total number of threads in contact with bone. It was concluded that the radiologic data overscored the real marginal bone level around screw-shaped oral implants, and that the Periotest device is neither able to discriminate between the first thread nor between the total number of threads in contact with bone.     

Crevicular fluid enzymes from endosseous dental implants and natural teeth

Several neutrophil-derived enzymes that are present in the gingival crevicular fluid have been evaluated for use as risk markers for periodontal disease progression. However, very little information is available about the presence of these enzymes in peri-implant tissues. The purpose of this cross-sectional study was to compare levels of enzymes in gingival crevicular fluid between natural teeth and endosseous dental implants and between well-integrated and failing implants. Scores of plaque and gingivitis were recorded for 68 integrated implants, five failing implants, and 34 natural teeth in 12 completely edentulous and 18 partially edentulous subjects. Samples of gingival crevicular fluid were obtained from these sites using filter paper strips and were assayed for levels of neutral protease, neutrophil elastase, myeloperoxidase, and beta-glucuronidase. Neutral protease levels were higher (P = .066) at moderately to severely inflamed implant sites (Gingival Index of 2, 3) compared to mildly or noninflamed sites (Gingival Index of = 0, 1). Despite the small number (n = 5) of failing implants evaluated in this study, levels of neutrophil elastase, myeloperoxidase, and beta-glucuronidase were significantly higher (P < or = .001) around failing implants compared to successful implants. Neutral protease levels were also elevated around failing implants, but the difference was not statistically significant. Results of this study indicate that neutrophil elastase, myeloperoxidase, and beta-glucuronidase levels in GCF appear to be good candidates for study as risk markers of implant failure.     

Proteoglycan expression by human trabecular meshworks

The aim of the present study was to clinically assess the peri-implant and periodontal conditions 1 year after placement of oral implants (ITI Dental Implant System) in partially edentulous patients. In all, 127 patients (median age 50 years, range 17 to 79) were examined. They were all treated according to a concept of comprehensive dental care and had received fixed partial dentures (FPD). Significant differences were observed between implants and contralateral control teeth with respect to mean pocket probing depth (PPD) (2.55 mm at implants/2.02 mm at teeth), mean probing attachment level (PAL) (2.97 mm/2.53 mm) and bleeding on probing (BOP) (24%/12%) (Wilcoxon matched pairs sign rank test, P < or = 0.01), whereas mean modified plaque index (0.22/0.30), mean modified bleeding index (0.35/0.44) and mean recession (-0.42 mm/-0.51 mm) did not significantly differ between implants and teeth. Compared to control teeth, the width of keratinized mucosa at implants was significantly smaller at lingual, but not at buccal aspects. Regression analyses showed no significant association between the amount of keratinized mucosa and degree of inflammation. Recession, PPD and PAL were slightly influenced by the amount of keratinized mucosa indicating greater resistance to probing. Grouping the implants according to various lengths, type of fixation of the FPD or combination with natural teeth did not result in statistically significant different clinical parameters, whereas grouping according to different localization within the oral cavity did. For example, the mean PAL in 83 anterior implants was 2.52 mm, whereas 175 posterior implants had a mean PAL of 3.18 mm (Mann-Whitney U-test, P < or = 0.01). Regression analyses between the mean PAL for all implants in each patient and the mean PAL of the corresponding dentition revealed an r2 of 0.23 (P < or = 0.01). Using multiple regression analysis, the mean PAL of the implants showed to be significantly influenced by the combined factors "fullmouth" PII, "fullmouth" BOP and mean PAL of all teeth. The results of this study suggest that in partially edentulous patients the overall periodontal condition may influence the clinical condition around implants and thus reinforces the importance of periodontal treatment prior to and supportive periodontal therapy after the incorporation of osseointegrated oral implants.     

New ideas and advancing technology in prevention and non-surgical treatment of periodontal disease

Analytical, oral epidemiological studies in adult 'toothbrushing' populations show that the highest prevalence of missing teeth is for molars and maxillary premolars ('key-risk' teeth). The highest prevalence of subgingival microflora, gingivitis (CPITN-1), plaque retentive factors, such as subgingival calculus and restoration overhangs (CPITN-2), and diseased pockets > 3 mm (CPITN-3-4) is found on the approximal surfaces of the same teeth ('key-risk' surfaces). Primary and secondary prevention, as well as treatment of periodontal disease should be focused on these 'key-risk' surfaces. One single, well-executed subgingival scaling and root-planning procedure in deep, diseased periodontal pockets, followed by oral hygiene training and professional mechanical tooth-cleaning (PMTC) at need-related intervals, will prevent further loss of periodontal attachment. However, if the root cementum is removed during instrumentation, and the post-treatment plaque control programme fails, microorganisms will recolonize and invade the rough exposed root dentine, resulting in recurrence of periodontitis and possibly, root caries and pulpitis. Some of these problems may be overcome by the application of new instruments and methods for self-care, PMTC, removal of overhangs, scaling and root-planing without removing 'non-diseased' cementum.     

Maintaining esthetic restorations in the periodontal practice

The aim of present study was to correlate the changes in the peri-implant tissues occurring after functional loading of non-submerged titanium implants and assessed by radiographic, clinical and mobility measurements. 11 patients with distal extension situations received 18 implants of the ITI Dental Implant System. After a healing period of 3 months, the suprastructures were fabricated and seated 5 months post-surgically. For the assessment of peri-implant bone changes, standardized vertical bitewing radiographs with reproducible exposure geometry were evaluated using computer assisted densitometric image analyses (CADIA) and bone height measurements. Since the radiographic evaluations were performed at mesial and distal sites only, the clinical parameters from these implant aspects were included in the analysis. Clinical periodontal parameters modified for the use around implants were obtained, damping characteristics were expressed as Periotest readings and standardized radiographs were obtained at 1, 3, 6, 12 and 24 months after loading. In addition, radiographs were also taken at the start of functional loading. The data obtained from this small sample of implants demonstrated a wide range of different tissue alterations when using radiographic, clinical and mobility assessments. The parameters of probing attachment level (PAL) in combination with radiographic parameters obtained at 1, 3, and 6 months after loading were good predictors for the peri-implant tissue status at 2 years. This was shown by means of multiple stepwise regression analyses. Mobility measurements did not reveal valuable predictive information with the statistical models applied. Assessments of probing attachment levels using periodontal probes rendered information on peri-implant tissue alterations, which were closely correlated to the radiographically measurable peri-implant bone changes.     

Effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in supra-alveolar peri-implant defects in dogs

This randomized, split-mouth design study evaluated the adjunctive effect of allogeneic, freeze-dried, demineralized bone matrix on guided bone regeneration in a critical-size, supra-alveolar, peri-implant defect model. Contralateral supra-alveolar peri-implant defects, 5 mm in height, each including two titanium implants, were surgically created in five beagle dogs. Demineralized bone matrix in autologous blood was placed over the implants in one randomly selected mandibular jaw quadrant. A space-making expanded-polytetrafluoroethylene membrane was used to provide guided bone regeneration bilaterally. Following a 16-week healing interval, tissue blocks were harvested and prepared for histometric analysis. Differences between experimental conditions (guided bone regeneration sites with and without demineralized bone) were evaluated using paired t tests (n = 4). Demineralized bone particles were discernible, with limited signs of resorption. The bone matrix particles appeared to be solidified within a dense connective tissue matrix and in close contact with the implants. Limited matrix remineralization was apparent adjacent to the alveolar crest. No statistically significant differences were found between experimental conditions for any parameter examined. Peri-implant defect height averaged 5.0 +/- 0.2 mm and 4.9 +/- 0.4 mm, vertical bone regeneration 1.5 +/- 0.9 mm and 1.1 +/- 0.4 mm, osseointegration within the extent of the defect 10.0 +/- 3.9% and 15.3 +/- 5.3%, osseointegration within the extent of regenerated bone 30.4 +/- 13.7% and 52.1 +/- 17.9%, and osseointegration within the alveolar base 68.8 +/- 13.1% and 74.4 +/- 7.1% for guided bone sites with and without demineralized bone, respectively (P > .05). The results suggest that freeze-dried demineralized bone has no adjunctive effect on guided bone regeneration in supra-alveolar peri-implant defects, that guided bone regeneration has a limited potential to enhance alveolar regeneration in this defect model, and that a 16-week healing interval appears insufficient for turnover and maturation of demineralized bone under provisions for guided bone regeneration.     

Osseointegration enhanced by chemical etching of the titanium surface. A torque removal study in the rabbit

Roughened implant surfaces are thought to enhance osseointegration. Torque removal forces have been used as a biomechanical measure of anchorage or osseointegration in which the greater forces required to remove implants may be interpreted as an increase in the strength of osseointegration. The purpose of this study was to compare the torque resistance to removal of screw shaped titanium implants having an acid etched (HC1/H2SO4) surface (Osseotite) with implants having a machined surface. Two custom screw shaped implants, 1 acid etched and the other machined, were placed into the distal femurs of 10 adult New Zealand White rabbits. These implants were 3.25 mm in diameter x 4.00 mm in length without holes, grooves or slots to resist rotation. Following a 2 month healing period, the implants were removed under reverse torque rotation with a digital torque measuring device. Two implants with the machined surface preparation failed to achieve osseointegration. All other implants were found to be anchored to bone. Resistance to torque removal was found to be 4 x greater for the implants with the acid etched surface as compared to the implants with the machined surface. The mean torque values were 20.50 +/- 6.59 N cm and 4.95 +/- 1.61 N cm for the acid etched and machined surfaces respectively. The results of this study suggest that chemical etching of the titanium implant surface significantly increases the strength of osseointegration as determined by resistance to reverse torque rotation.     

Implant reconstruction of the jaws and craniofacial skeleton

Full oral rehabilitation with a high degree of success is now possible with osseointegrated implants. Osseointegration is a direct connection between living bone and the titanium implant at the level of the light microscope. Osseointegrated implants are currently used to replace single teeth, support fixed bridges and stabilize full dentures. These implants can also be placed extraorally for attachment of facial prosthesis. The surgical technique used to place implants intraorally into jaws or facial skeleton is performed in two stages using a local anesthetic and/or conscious sedation. During stage I surgery, holes are placed into the jaw using a series of gradually larger diameter burs until the desired diameter and depth of the bony preparation is achieved. The implant is then placed. The implant must remain undisturbed for 4 months for osseointegration to take place. Stage II surgery is then required to remove the mucosa over the implant and place the transmucosal abutment. After 1-2 weeks of healing, the restorative dentist can take an impression and fabricate the prosthesis. On occasion, it is necessary to augment the height and width of the atrophic jaw with autogenous or allogeneic bone grafts prior to implant placement. Bone grafts are sometimes placed on the floor of the nose or the floor of the maxillary sinus. Guided tissue regeneration is a technique used to generate bone within bony defects adjacent to implants. With long-term rates of success (5 years) of 99% for implants placed in the mandible and 95% for those placed in the maxilla, reconstruction of the jaws and cranial facial skeleton with osseointegrated implants has become the treatment of choice.     

Bone SPECT of the jaws after fracture, onlay osteoplasty of insertion of implants

AIM: The aim of this study was early differentiation between uncomplicated and complicated processes of healing in the jaw using bone SPECT. METHODS: Investigations were performed in 40 mandibular fractures and 26 jaws after onlay osteoplasty as well as secondary insertion of implants. Bone SPECT was carried out within 1-2 months and after approximately 4-5 months. The uptake in the jaw was assessed semi-quantitatively using ROI analysis. RESULTS: Fractures with uncomplicated healing showed a decrease of uptake in follow-up, whereas fractures with an infection in the later course showed an increase, resulting in a significantly higher uptake at the follow-up investigation for the latter group. 1-2 months after onlay osteoplasty significantly lower uptake was found in regions with later occurrence of sequestration. In regions with implants in which osseointegration failed, there was significant reduction of uptake initially and significant elevation at the follow-up investigation. CONCLUSION: These results indicate a prognostic relevance of bone SPECT in the evaluation of processes of healing in the jaw.     

The evolution of clinical periodontal therapy

Periodontal diseases are considered as old as the history of mankind, Magical, religious and herbal treatments were demonstrated in almost all of the early writings. However, methodical, carefully reasoned therapeutic approaches did not exist until the middle-ages and modern treatment with a scientific base and sophisticated instrumentation did not develop until the 18th century. Prior to the 1950s, diseases were mostly treated by root debridement and the extraction of the affected teeth. Until the 1970s, it was primarily the symptoms of periodontal diseases that were treated. The goal was radical elimination of the periodontal pocket (resective therapy). The means were gingivectomy, flap procedures and osseous surgery. The disadvantages were the massive sacrifice of periodontal tissues, lack of regeneration and clinically elongated teeth. These disadvantages, along with the realization of the importance of aetiologic agents, raised questions about the necessity of total pocket elimination, and the control of subgingival infection by a thorough scaling and root planing (nonsurgical therapy), with and without antibiotics, became a commonly used treatment during the 1980s. Comparative longitudinal studies, surgical versus nonsurgical, demonstrated that both surgical and nonsurgical therapy result in limited regeneration and healing with a long junctional epithelium. The most important aspects of today's modern concept of periodontal therapy are causal, regenerative, and specific for disease type and severity. Although the regeneration of the periodontium can be accomplished with the biological principles of guided tissue regeneration and graft materials, compared to conventional methods, the restoration of a completely normal periodontal status has not yet been achieved. We are about to reach our ultimate goals and presently, the more promising research directions for a substantial regeneration seems to lie in biological mediators. Although the future of periodontal therapy is bright, it is still of critical importance to have a preventive strategy to keep individuals healthy beforehand.