Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.

The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.

Clinical evaluation of tetracycline HCl conditioning in the treatment of gingival recessions. A comparative study.

Thirty Class I and Class II recessions in 30 patients were treated with a modified subepithelial connective tissue graft procedure. Fifteen recessions in the test group received a tetracycline hydrochloride (50 mg/ml) root treatment for 5 minutes (TTC-HCl group); the remaining 15 recessions composed the control group and received a citric acid root treatment for 3 minutes (CA group). Clinical assessments were taken at baseline and at 6 months. The differences between treatments were not statistically significant. In the central area of the recession, the mean percentage of root coverage was 81.7% corresponding to a mean percentage of 79.3% and 84.0% for the TTC-HCl and the CA group, respectively. In the test group, 6 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 57.8%. In the control group, 8 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 43.6%. The mean surface area of root exposure was reduced from 11.53 mm2 and 13.30 mm2 to 0.34 mm2 and 0.29 mm2 for the TTC-HCl group and the CA group, respectively. This reduction corresponds to a mean percentage of 97.4% root coverage for both groups. Within the limits of this study, the results indicate that tetracycline hydrochloride and citric acid root conditioning have comparable clinical effects in root coverage surgical therapy. The data also suggest that the measurement of the surface area of the recession is a more accurate criterion in the evaluation of the mean percentage of root coverage than a single central vertical linear measurement.

Subepithelial connective tissue grafts in the treatment of gingival recessions. A comparative study of 2 procedures.

Thirty (30) class I and class II recessions in 30 subjects were treated with a subepithelial connective tissue graft procedure. In one group (15 sites), the surgery was carried out in a traditional fashion: the epithelial collar of the graft was preserved and left exposed (CTG group). In the second group (15 sites), the epithelial collar of the graft was removed and the recession areas were conditioned with citric acid. The graft was then sutured and completely immersed under the facial flap which was coronally repositioned (CR group). Clinical assessments included probing depth, probing attachment level, surface area of the recession, and gingival width. These measurements were taken at baseline and at 6 months. In addition, an esthetic evaluation was done. The differences between treatments were not statistically significant except for the augmentation of gingiva (P < or = 0.05). Based on the midfacial measurements taken in the central area of the recession, the mean percentage of root coverage was 69.2%. In the CR group, 3 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 65.5%. In the CTG group, 5 of the 15 recessions exhibited complete root coverage; the gingival augmentation was 94.4%. The mean surface area of root exposure was reduced from 13.82 mm2 and 13.67 mm2 to 2.15 mm2 and 2.34 mm2 for the CR group and the CTG group, respectively. One-hundred percent (100%) of good-to-moderate esthetic results were found by a panel of independent examiners; there was tendency toward better results in the CR group.(ABSTRACT TRUNCATED AT 250 WORDS)

Expanded polytetrafluoroethylene membranes and connective tissue grafts support bone regeneration for closing mandibular Class II furcations.

Twenty-four mandibular buccal Class II furcation lesions in 12 subjects were treated with reconstructive periodontal therapy including citric acid root treatment and replaced flap surgery. Twelve (12) of the lesions received expanded polytetrafluoroethylene (ePTFE) membranes to cover the furcation entrance (ePTFE group) whereas the remaining 12 lesions received a connective tissue graft over the furcation (CTG group). Clinical assessments, including probing depth, probing attachment level, location of gingival margin, direct bone probing, and defect volume, were taken at baseline and at 12 months reentry. In the ePTFE group 30% of the defect volume filled with bone; 36% of the defects exhibited complete bone closure. In the CTG group 19% of the defect volume filled with bone and 18% of these defects exhibited complete bone closure. There were no meaningful clinical differences between treatment groups except in horizontal probing depth change (P < or = 0.05). This study suggests that connective tissue grafts and ePTFE membranes have comparable potential in supporting bone regeneration in mandibular Class II furcation lesions. Further clinical trials with larger numbers of patients and a longer evaluation period are needed to fully compare these procedures.

Periodontal repair in dogs: expanded polytetrafluoroethylene barrier membranes support wound stabilization and enhance bone regeneration.

A wound stabilizing effect of expanded polytetrafluoroethylene (ePTFE) membranes was evaluated in supra-alveolar periodontal defects in 5 beagle dogs. The defects, 5 to 6 mm in height, were surgically created around the 2nd, 3rd, and 4th mandibular premolar teeth in contralateral jaw quadrants. The root surfaces were conditioned with heparin, which, in this model, has been demonstrated to compromise periodontal healing and result in formation of a long junctional epithelium. Wound closure included application of ePTFE membranes around each premolar tooth in one jaw quadrant in each dog and flap positioning coronal to the cemento-enamel junction in both jaw quadrants. Healing progressed uneventfully except for 3 teeth in 2 dogs, which experienced membrane exposure. The dogs were sacrificed after a 4-week healing period and tissue blocks were prepared for histometric analysis. Connective tissue repair in heparin+membrane-treated teeth averaged 98% of the defect height compared to 84% in control heparin-treated teeth (P < or = 0.05). Junctional epithelium formation was smaller in membrane-treated teeth than in control teeth (P < or = 0.05) and was usually terminated coronal to the membrane. Bone regeneration was enhanced in membrane-treated teeth compared to controls (P < or = 0.01) and was strongly correlated to the area under the membrane in teeth without membrane exposure (r2 = 0.993; P = 0.002). This correlation was reduced when teeth with membrane exposure were included in the analysis (P < or = 0.05). Cementum regeneration was minimal under both treatment conditions. Root resorption was increased in membrane-treated compared to control teeth (P < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a collagen matrix on healing in periodontal fenestration defects in dogs.

Contralateral periodontal fenestration defects in seven beagle dogs were used to evaluate influence of a collagen matrix on periodontal wound healing. The defects (6 x 4 mm) were created through the buccal cortical plates of the maxillary canine teeth following elevation of mucoperiosteal flaps. The collagen was fitted to the defects on one side. Contralateral defects served as controls. Flaps were repositioned and sutured. Dogs were sacrificed 4 weeks after surgery and block sections including teeth and surrounding structures were prepared for histometric analysis. No meaningful differences in cementum and bone regeneration were observed between treatments. There was seemingly more bone regeneration in the apical than in the coronal aspect of the defects and significantly more cementum regeneration. Root resorption was observed in one collagen and one control defect. Ankylosis was not observed. The results suggest that the maxillary canine periodontal fenestration defect can be used as a model to evaluate factors that may enhance cementum and bone regeneration. The collagen matrix neither enhanced nor inhibited periodontal wound healing in this model.

Treatment of periodontal furcation defects. Coronally positioned flap with or without citric acid root conditioning in class II defects.

A total of 27 mandibular, buccal class II furcation defects were treated in 16 subjects using a coronally positioned flap procedure, with or without citric acid conditioning of the root surfaces. The effect of the therapies was evaluated from a series of soft and hard tissue measurements. Mean improvements were slightly greater for acid treated than for non-acid treated defects. However, none of the mean differences reached statistical significance, indicating that citric acid conditioning may not be a necessary part of the regenerative, coronally positioned flap procedure in mandibular furcations.

Regenerative surgery of intrabony periodontal defects using ePTFE barrier membranes: scanning electron microscopic evaluation of retrieved membranes versus clinical healing.

Sixteen intrabony defects in 12 patients were treated by gingival flap surgery including root surface debridement and placement of an expanded polytetrafluoroethylene (ePTFE) membrane. The membranes were removed after 4 to 6 weeks and examined by scanning electron microscopy (SEM) for bacterial contamination and adherent connective tissue elements. Twelve months postsurgery, the defect sites were reexamined for changes in probing attachment level and probing bone level. Comparison of ultrastructural findings and clinical observations revealed that extent of bacterial contamination of the membrane correlated inversely with clinical assessment of attachment gain. The results indicate that the extent of oral exposure and bacterial contamination of the ePTFE membrane at the time of removal may be an indicator of the long-term success or failure of the regenerative procedure.

Healing of the intrabony periodontal lesion following root conditioning with citric acid and wound closure including an expanded PTFE membrane.

The effect of citric acid conditioning of the root surface in conjunction with gingival flap surgery including barrier membranes (expanded polytetrafluoroethylene) was clinically evaluated in 26 intrabony periodontal defects in 23 patients. Control treatment included gingival flap surgery with barrier membranes alone. Twelve defects were treated with the experimental and 14 with the control protocol. Healing was evaluated 12 months after surgery. Initial probing depths approximated 6.9 mm and defect depths measured during surgery exceeded 4 mm. The patients exhibited good oral hygiene over the study interval as substantiated by low plaque and bleeding scores. Acid conditioning of the root surface did not enhance periodontal healing in this study, similar amounts of defect resolution were observed following either treatment protocol. Probing depth reduction generally approximated 1.8 mm; gain of clinical attachment, 0.8 mm; and defect bone fill, 1.2 mm. Under the prevailing conditions, the barrier membrane procedure apparently gave a healing result beyond which further improvement could not be achieved by root surface conditioning.

The effect of hygiene instruments on dentin surfaces: scanning electron microscopic observations.

The present study consists of two separate parts. The first section is an in vitro evaluation of the relative abrasiveness of some hygiene instrumentations commonly used during maintenance therapy. In the second section, one of the instruments, a recently developed plastic tip for use on a sonic scaler, was examined for its ability to remove dental plaque from root surface specimens instead for 5 weeks in the oral cavities of dogs. The in vitro study was performed on recently obtained dentin specimens where a ridge had been machined parallel to the long axis of the tooth. The sonic scaler fitted with the plastic tip gave considerably less removal of dentin and a smoother dentin surface than the curet, the rubber cup with polishing paste, or the sonic scaler with an ordinary metal tip. These findings further demonstrated that the plastic tip was able to efficiently remove 5-week old dental plaque from experimental root surface areas within a time frame of 5 seconds. The new plastic tip may be valuable in maintenance therapy giving less risks for iatrogenic effects on the root surfaces than other debridement methods.

Significance of early healing events on periodontal repair: a review.

Wound healing in an incisional wound is a highly predictable process which has been studied extensively hour-by-hour and day-by-day. Healing in a periodontal defect following gingival flap surgery is, conceptually, a more complex process as one wound margin consists of calcified tissue, including the avascular and rigid root surface. Another complicating factor in this wound healing is the transgingival position of the tooth. Experimental studies, however, have indicated that healing at a dento-gingival interface under optimal conditions occurs at the same rate as in a skin wound. Generally, periodontal healing is characterized by maturation of gingival connective tissue, limited regeneration of alveolar bone and cementum, and the formation of a long junctional epithelium. Such observations have nurtured the hypothesis that the epithelium of the surgical flap needs to be prevented from early access to the root surface during the healing period to achieve connective tissue repair of the root surface-gingival flap interface. Recent experimental findings suggest, however, that connective tissue repair to the root surface following reconstructive periodontal surgery is a function of the establishment and maintenance of a root surface-adhering fibrin clot. Since fibrin adherence to the wound margins is a natural event, it is additionally suggested that apical migration of the gingival epithelium in periodontal surgical wounds may only follow interruption of the adherence of the fibrin clot to the root surface.

Periodontal repair in dogs: effect of a composite graft protocol on healing in supraalveolar periodontal defects.

This study evaluated the effect of a composite graft as an adjunct to gingival flap surgery in induced chronic supraalveolar periodontal defects in the mandibular premolar region in beagle dogs. The vertical dimension of the defects, measured from the cemento-enamel junction to the alveolar bone, approximated 5 mm. Root surface treatment in quadrants receiving the graft protocol included conditioning with both critic acid and tetracycline. The composite graft (including: hydroxyapatite, freeze-dried decalcified bone, tetracycline, and fibronectin) was then fitted to the defects. Flaps were placed and sutured to cover most of the crowns of the teeth but the tips of the cusps. The root surfaces in contralateral jaw quadrants were conditioned with critic acid and the flaps similarly placed and sutured. Dogs were sacrificed 6 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histometric analysis. Connective tissue repair to the root surface in teeth treated with the graft protocol approximated 60% of the defect height. Connective tissue repair in teeth treated with citric acid only was significantly greater and averaged 98% of the defect height (P less than or equal to 0.01). Cementum formation was limited following both treatments (approximately 6% of the defect height). Bone regeneration was significantly smaller in grafted sites than in sites treated with citric acid only (approximately 2% and 10% of the defect height, respectively; P less than or equal to 0.05). Root resorption was observed in almost all teeth. Ankylosis was present in two citric acid-treated specimens, both from the same dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Periodontal repair in dogs: healing in experimentally created chronic periodontal defects.

A need exists for well-defined animal models to objectively evaluate surgical principles and a possible role for biochemical wound conditioning and biomaterials in promoting periodontal regeneration. To test an existing model for its usefulness in quantitative evaluation of periodontal wound healing, large supraalveolar periodontal defects were surgically created around the mandibular premolars (P2, P3, P4) in left or right jaw quadrants in 5 beagle dogs. The defects were exposed to the oral environment for 6 months and were then subjected to reconstructive flap surgery (chronic defects). Healing in these defects was compared to healing following reconstructive surgery in similar contralateral defects which had not been exposed to plaque and calculus (acute defects). The animals were sacrificed after a 4-week healing period and tissue blocks including teeth and surrounding structures were processed for histometric analysis. Mean defect height (+/- s.d.) for chronic and acute defects amounted to 4.6 +/- 0.3 and 4.4 +/- 0.4 mm, respectively. Mean connective tissue repair to the root surface in chronic defects amounted to 62% (range 49% to 74%) of the defect height. Mean connective tissue repair in the acute defects exceeded 94% of the defect height in 4 of the dogs, but amounted to only 48% in 1 dog. Regeneration of alveolar bone and cementum was limited under both experimental conditions. Root resorption was frequently encountered, whereas ankylosis was seen in only few teeth. This study indicates that healing may vary not only as a result of controlled experimental variables, but also due to differences in biological response between dogs or to fortuitous traumatic factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Periodontal repair in dogs: effect of root surface treatment with stannous fluoride or citric acid on root resorption.

This study evaluated healing, with emphasis on root resorption, following root surface treatment with 1% aqueous stannous fluoride (SnF2), saturated citric acid (CA), or saline control (C) in conjunction with periodontal flap surgery. Supraalveolar periodontal defects were surgically created and immediately treated in the mandibular premolars in 6 beagle dogs. The defect height approximated 5 to 6 mm from the reduced alveolar bone to the cemento-enamel junction. Root treatments were rotated between experimental teeth within jaw quadrants and duplicated in left and right quadrants in the dogs. Flaps were raised to cover most of the crowns of the teeth and sutured. The dogs were sacrificed 12 weeks after surgery and tissue blocks with teeth and adjacent structures were processed for histometric analysis. SnF2-treated teeth healed with significantly longer junctional epithelium, less connective tissue repair to the root surface, and less bone regeneration than CA and C-treated teeth. New cementum formation was limited in all treatment groups. Root resorption was observed in almost all teeth exhibiting connective tissue repair, however to a lesser amount and not as frequent in SnF2 treated teeth due to limited connective tissue repair. No differences were found in amount and frequency of root resorption in CA and C-treated teeth. An inhibitory effect on root resorption of SnF2 could not be disclosed in this experiment, however, it may be concluded that CA treatment of the root surface in conjunction with reconstructive periodontal flap surgery does not seem to enhance root resorption.

Periodontal repair in dogs. Healing patterns in large circumferential periodontal defects.

This report describes the healing patterns of large circumferential periodontal defects in the beagle dog. Approximately 5 mm large periodontal defects were created around the mandibular premolars (P2, P3 and P4) in 13 animals. The root surfaces were then instrumented to remove all cementum and the wounds immediately closed by replacing and suturing the flaps just coronal to the cemento-enamel junction. Block biopsies were harvested after 4 weeks. Most of the surgically denuded root surface healed with connective tissue repair. Cementum formation and regeneration of alveolar bone was limited and averaged approximately 30% and 20%, respectively, of the defect height. Almost all teeth exhibited root resorption. Ankylosis was observed in 1/3 of the teeth. There was no difference in the healing response between the 3 premolars or their buccal and lingual surfaces. The range of healing responses indicates that a biological potential exists which makes this model useful for testing the effect of various root and wound conditioners in (1) enhancing cementum formation on the root surface, (2) increasing regeneration of alveolar bone and (3) preventing aberrant healing events such as root resorption and ankylosis. Conversely, whether such agents may compromise wound healing and result in reduced connective tissue repair may concomitantly be tested.

Early healing events at the dentin-connective tissue interface. Light and transmission electron microscopy observations.

The objective of these studies was to follow early healing at the dentin-connective tissue interface. Small dentin blocks were surgically implanted in bone cavities under mucoperiosteal flaps in the edentulous alveolar ridges of five beagle dogs at various times. In two separate experiments, wound maturation on native dentin surfaces and on citric acid or heparin conditioned dentin surfaces was observed. Block specimens including bone, dentin, and surrounding soft tissues were obtained at 10 minutes, 1 and 6 hours, and 1, 3, and 7 days after flap closure and prepared for light and transmission electron microscopic examination of the interface. The very initial attachment to native dentin was mediated by a granular precipitate. At 1 and 6 hours, the intercellular matrix was more organized with fibrin formation around red blood cell aggregates and at the dentin surface. Polymorphonuclear leukocytes were observed throughout the interface. Red blood cells were undergoing degradation at day 1 and polymorphonuclear cells were prevalent at the dentin surface. The 3-day observation interval was characterized by further maturation of the fibrin clot. Macrophages were observed near the dentin surface and fibroblasts could be identified. The 7-day specimens exhibited areas of cell rich connective tissue attachment without inflammatory cells as well as areas showing the fibrin clot in various stages of decomposition. These observations suggest that connective tissue attachment to dentin surfaces is mediated by adsorption of plasma proteins to the surface and subsequent development and maturation of a fibrin clot. The sequence of healing events at dentin surfaces conditioned with citric acid or heparin was largely similar to healing at native dentin surfaces. However, at day 1 and later time points, clot adhesion to heparin-conditioned dentin appeared compromised, whereas the fibrin clot seemed to adhere to citric acid-conditioned dentin at all observation periods. These observations indicate that in the absence of mechanical trauma, epithelial proliferation, and infection, wound maturation at the dentin-connective tissue interface may not necessarily be affected by treatments that either enhance or inhibit clot adhesion to the dentin surface.

Periodontal repair in dogs: effect of wound stabilization on healing.

This study evaluated a biodegradable polylactic acid matrix as a wound stabilizing implant in reconstructive periodontal surgery. Supra-alveolar circumferential periodontal defects, 5 to 6 mm large, were surgically created around the mandibular premolars in 7 beagle dogs. The root surfaces in left and right jaw quadrants were treated with either heparin or saline. In this model, root surface treatment with heparin compromises periodontal repair and results in a long junctional epithelium and a reduced connective tissue repair to the root surface, whereas saline treatment results in almost complete connective tissue repair. Following heparin or saline treatment a polylactic acid implant was placed on 1 premolar in each quadrant. After 4 weeks of wound healing, the dogs were sacrificed and tissue blocks prepared for histometric analysis. Postoperatively, the implant became exposed and infected in 3 dogs and had to be removed. Therefore, the results reflect the 4 dogs in which healing progressed uneventfully. Connective tissue repair to the root surface in teeth treated with heparin averaged 82% of the defect height. Mean connective tissue repair in teeth treated with heparin and the implant was significantly greater and comprised approximately 99% of the defect height (P less than 0.05). Teeth treated with saline either with or without the implant also healed with almost complete connective tissue repair. The results support the importance of wound stabilization in periodontal wound healing. Development of biodegradable implant systems aimed at stabilizing and supporting the healing wound seems a desirable direction for future research in regenerative periodontal procedures.

Scanning electron microscopic observations of cell populations and bacterial contamination of membranes used for guided periodontal tissue regeneration in humans.

Fourteen intrabony periodontal defects and six furcation defects (Class II) were treated by a flap procedure which included the use of a polytetrafluoroethylene membrane to allow guided tissue regeneration. After 4 to 6 weeks of healing, the membranes were retrieved and examined by scanning electron microscopy for the presence of adherent cells and other tissue elements. The cervical open pore-structured collar of the membrane, which in most cases had become partially exposed to the oral cavity, had a deposit of bacterial plaque. Bacterial Bacterial colonies and a scatter of single cells in some instances extended into the mid-third of the membrane. Fibroblast-like cells and, in some specimens, blood vessels and fibrous structures were seen in the mid-third and deep parts of the membrane. Generally, however, the occlusive portion of the membrane was characterized by a sparseness of adherent tissue elements. There did not seem to be a systematic difference in the nature and distribution of the adherent structures on the inner and outer surfaces of the membrane. The findings suggest that, in addition to preventing flap tissues from contacting the root surface, an important function of the membrane is to protect the integrity of the underlying blood clot by diverting mechanical stress acting on the flap during early stages of healing.

5-year follow up of periodontal intraosseous defects treated by root planing or flap surgery.

Intraosseous, periodontal defects in 12 subjects initially treated by root planing alone (21 defects) or by flap surgery (21 defects) were monitored during a 5-year postoperative interval. Maintenance therapy during this interval was limited to reinforcement of oral hygiene and tooth polishing every 6 months. No subgingival instrumentation was performed at the defect sites. Longitudinal clinical measurements demonstrated that surgically-treated lesions responded with somewhat more reduction of probing depth and more gain of probing bone level than root-planed lesions. Mean gains of probing attachment level were similar for the 2 treatments. Some relapse of the clinical conditions could be observed towards the end of the 5-year observation interval compared to the results at year 1 and year 2. However, the majority of defects subjected to either treatment showed 60-month recordings of probing attachment and probing bone levels equal to or slightly improved compared to those at baseline. Counts from cultures of subgingival, microbial samples were obtained at 42, 48 and 60 months. No significant difference between the 2 therapies was observed for the investigated groups of micro-organisms.