Variables that influence the relationship between osseointegration and bone adjacent to an implant.

It is often assumed that there is a direct relationship between the bone density adjacent to an implant, as revealed by radiographs, and the percent histologic osseointegration. Moreover, the lack of standardized methods for evaluation of histologic preparations makes it difficult to compare published studies, especially as little is known about the variables that influence these measurements. In this animal study, computer-assisted lineal analysis was used to evaluate the effects of subject, tooth position, and implant surface site on measured bone density and osseointegration in a bone augmentation experiment. Three sites--coronal lingual, apical lingual, and apical facial--were analyzed around each of 6 (3.75 x 8 mm) threaded machined titanium implants, as well as the apical facial site of 21 other implants placed in the mandibular premolar area of 5 dogs. In all sites, a progressive decrease in bone density was observed from bone adjacent to the implant to that at the titanium implant surface. There was an animal effect on osseointegration, but there were no differences between the mandibular premolar locations (second, third, and fourth). Most importantly, there were significant measurable effects attributable to the surface site examined. The need for carefully standardized histologic evaluations is established.

The effect of locally delivered controlled-release doxycycline or scaling and root planing on periodontal maintenance patients over 9 months.

BACKGROUND: This research report evaluates clinical changes resulting from local delivery of doxycycline hyclate (DH) or traditional scaling and root planing (SRP) in a group of patients undergoing supportive periodontal therapy (SPT). METHODS: In all, 141 patients received either DH (67) or SRP (74) treatment in sites > or =5 mm on one-half of their dentition at baseline and month 4. RESULTS: Clinical results were determined at month 9. Baseline mean probing depth recordings were similar between the two groups (DH = 5.9 mm; SRP = 5.9 mm). Mean month 9 results showed similar clinical results for attachment level gain (DH 0.7 mm; SRP 0.8 mm) and probing depth reduction (DH 1.3 mm; SRP 1.1 mm). Percentage of sites showing > or =2 mm attachment level gain at month 9 was 24.7% in the DH group and 21.2% in the SRP group. Thirty-nine percent (39%) of DH sites and 38% of SRP sites showed > or =2 mm probing depth reduction. When treated sides of the dentition were compared to untreated sides, DH showed a difference in disease activity (> or =2 mm attachment loss) from 19.3% (untreated) to 7.2% (treated); and SRP from 14.3% (untreated) to 8.1% (treated). CONCLUSIONS: Results show that both DH without concomitant mechanical instrumentation and SRP were equally effective as SPT in this patient group over the 9-month study period.

Effects of smoking on local delivery of controlled-release doxycycline as compared to scaling and root planing.

This paper examines the effects of smoking on the treatment outcomes of two nonsurgical therapies: (1) scaling and root planing alone (SRP) or (2) controlled-release of subgingivally delivered doxycycline hyclate in a polylactic acid based polymer gel. Subjects from 2 9-month multicenter studies were classified as nonsmokers (never smoked: 100 subjects), former smokers (137 subjects), and current smokers (> or = 10 cigarettes/day: 121 subjects). Clinical parameters were analyzed for treated sites with baseline probing depths > or = 5 mm and for a subset of treated sites with baseline probing depths of > or = 7 mm. Clinical parameters (plaque levels, clinical attachment levels, pocket depths, and bleeding on probing) were analyzed at baseline, 4, 6, and 9 months. In the doxycycline treated group in general, there were neither marked significant differences in clinical attachment gain nor differences in probing depth reduction among the 3 smoking groups. On the other hand, in the scaling and root planing treated group in general, there were significant differences in clinical attachment gain and pocket depth reduction, with non-smokers responding better than former smokers and current smokers at 6 and 9 months. These differences in clinical response between scaling and root planing alone versus controlled-release of locally-delivered doxycycline hyclate among these 3 smoking groups are discussed in relation to treatment implications for smokers.

Two multi-center studies evaluating locally delivered doxycycline hyclate, placebo control, oral hygiene, and scaling and root planing in the treatment of periodontitis.

BACKGROUND: The clinical efficacy and safety of doxycycline hyclate (8.5% w/w) delivered subgingivally in a biodegradable polymer (DH) was compared to placebo control (VC), oral hygiene (OH), and scaling and root planing (SRP) in 2 multi-center studies. METHODS: Each study entered 411 patients who demonstrated moderate to severe periodontitis. Patients had 2 or more quadrants each with a minimum of 4 qualifying pockets > or =5 mm that bled on probing. At least 2 of the pockets were > or =7 mm. Treatment with DH, VC, OH, or SRP was provided at baseline and again at month 4. Clinical parameters were recorded monthly. RESULTS: DH and SRP resulted in nearly identical clinical changes over time in both studies. Mean 9 month clinical attachment level gain (ALG) was 0.8 mm for the DH group and 0.7 mm for the SRP group in Study 1, and 0.8 mm (DH) and 0.9 mm (SRP) in Study 2. Mean probing depth (PD) reduction was 1.1 mm for the DH group and 0.9 mm for the SRP group in Study 1 and 1.3 mm for both groups in Study 2. Frequency distributions showed an ALG > or =2 mm in 29% of DH sites versus 27% of SRP sites in Study 1 and 31% of DH sites versus 34% of SRP sites in Study 2. PD reductions > or =2 mm were seen in 32% of DH sites versus 31% of SRP sites in Study 1 and 41% of DH sites versus 43% of SRP sites in Study 2. Comparisons between DH, VC, and OH treatment groups showed DH treatment to be statistically superior to VC and OH. Safety data demonstrated a benign safety profile with use of the DH product. CONCLUSIONS: Results of this trial demonstrate that treatment of periodontitis with subgingivally delivered doxycycline in a biodegradable polymer is equally effective as scaling and root planing and superior in effect to placebo control and oral hygiene in reducing the clinical signs of adult periodontitis over a 9-month period. This represents positive changes resulting from the use of subgingivally applied doxycycline as scaling and root planing was not limited regarding time of the procedure or use of local anesthesia.

Locally delivered doxycycline hyclate: case selection, preparation, and application.

This article presents the perspective of a private practice clinician who participated in the phase III clinical trials of Atridox (doxycycline hyclate) 10%. The selection of periodontal cases most likely to benefit from treatment with Atridox as part of overall comprehensive case management is discussed. Atridox may be used either before or after scaling and root planing or, in more rare circumstances, as a stand-alone therapy. Preparation of the material is discussed, and guidance for optimal application is provided.

Biodegradation and biocompatibility of a guided tissue regeneration barrier membrane formed from a liquid polymer material.

Biodegradable barrier films were made by coagulating a solution of poly(DL-lactide) in N-methyl-2-pyrrolidone on porous polyethylene pads wetted with saline solution. The semisolid films were cut into 10 x 10 mm barriers and implanted subcutaneously in rabbits. At monthly intervals, the polymer implant sites were compared histologically to those implanted with USP negative control plastic. The polymer films were retrieved from the surrounding tissue, dried, weighed, and the changes in molecular weight determined using gel permeation chromatography. The molecular weight of the polymer decreased at a relatively constant rate over 5 months; however, no significant mass loss occurred until 5 months postimplantation. Also, no distinct histological differences were noted between the polymer barrier and the control plastic sites until 6 months when histiocytes and multinucleated giant cells showed a modest increase around fragmented polymer films. Similar barrier films also were fitted over naturally occurring buccal dehiscence defects in beagle dogs and the tissue sites compared histologically at 6 months to sham-operated control sites. New bone and dense connective tissues closely approximated segments of the remaining polymer and demonstrated the biocompatibility of the biodegradable films. Histomorphometric analyses of treated sites compared to sham controls showed that the polymer barrier is effective in promoting bone and cementum regeneration in periodontal defects in dogs.

Comparison of a bioabsorbable GTR barrier to a non-absorbable barrier in treating human class II furcation defects. A multi-center parallel design randomized single-blind trial.

This multi-center single-blind study compared clinical outcomes following guided tissue regeneration (GTR) treating human Class II furcation defects with a new polylactic-acid-based bioabsorbable barrier (test treatment) or a non-absorbable ePTFE barrier (control treatment). Clinical parameters evaluated were change in vertical attachment level (VAL), horizontal attachment level (HAL), probing depth (PD), and gingival margin location (REC). Surgical treatment resulted in clinically and statistically equivalent changes when comparisons were made between test and control treatments. VAL gain was 2.0 mm for test and 1.6 mm for control groups; HAL gain was 2.1 mm for both test and control groups. PD reduction was 2.3 mm for the test group and 2.1 mm for the control group. Test sites experienced an additional 0.3 mm of recession beyond baseline; control sites, 0.5 mm. Within-group comparisons showed that the amount of recession was not significantly different from baseline in the test group. Recession in the control group was significantly different from baseline. All other parameters in both the test and control groups were significantly different from baseline. Evaluation of safety data indicated no significant differences between test and control treatments, although there was a strong trend for the control group to have more postoperative abscess or suppuration than test sites (control = 11; test = 4; P = 0.06).

Periodontal regeneration in naturally occurring Class II furcation defects in beagle dogs after guided tissue regeneration with bioabsorbable barriers.

THE EFFICACY OF A BIOABSORBABLE polylactic acid based barrier was evaluated using naturally occurring buccal Class II furcation defects in beagle dogs. Sixteen furcation sites (8 control and 8 experimental) were treated in 6 adult animals. After full thickness flap reflection, exposed furcations and root surfaces were thoroughly root planed. In experimental sites a customized barrier was formed and fitted to cover the defect. Surgical flaps were replaced slightly coronal to the cemento-enamel junction. Animals were sacrificed at 6 months and specimens processed for histologic evaluation. Histologic and histometric analyses were done using 6 micrograms step serial sections in the buccal-lingual plane, corresponding to the buccal-lingual extent of the furcation. Results were: mean total defect experimental sites 1.92 mm; control sites 1.47 mm. Mean new cementum formation experimental sites 1.36 mm (71% of initial defect); control sites 0.25 mm (17% of initial defect). Mean new bone formation experimental sites 1.42 mm (74% of initial defect); control sites 0.20 mm (14% of initial defect). Mean junctional epithelium formation experimental sites 0.42 mm (22% of initial defect); control sites 1.21 mm (82% of initial defect). Statistical analysis demonstrated significant differences in all healing parameters favoring experimental (barrier-treated) sites. In this model, regeneration (new bone, cementum, and periodontal ligament) of 71% of the original defect in experimental sites and only 14% in control sites demonstrated a response that highly favored use of the barrier.

Multi-center comparative evaluation of subgingivally delivered sanguinarine and doxycycline in the treatment of periodontitis. II. Clinical results.

The clinical safety and effectiveness of a subgingivally delivered biodegradable drug delivery system containing either 10% doxycycline hyclate (DH), 5% sanguinarium chloride (SC) or no agent (VC) was evaluated in a 9-month multi-center trial. The study was a randomized parallel design with 180 patients who demonstrated moderate to severe periodontitis. All patients had at least two quadrants with a minimum of four qualifying pockets > or = 5 mm that bled on probing. Two of the qualifying pockets were required to be > or = 7 mm. At baseline and at 4 months all qualified sites were treated with the test article administered via syringe. Probing depth reduction (PDR), attachment level gain (ALG), bleeding on probing reduction (BOP), and plaque index were determined monthly. Analysis of efficacy data from the 173 efficacy-evaluable patients indicated that all treatments gave significant positive clinical changes from baseline at all subsequent timepoints. DH was superior to SC and VC in PDR at all timepoints (P < or = 0.01 to 0.001) with a maximum reduction of 2.0 mm at 5 months. For ALG, DH was superior to VC at months 2, 3, 4, 5, 6, 8, and 9 (P < or = 0.04 to 0.002) and superior to SC at months 5, 6, 7, 8, and 9 (P < or = 0.01 to 0.001) with a maximum ALG of 1.2 mm at 6 months. For BOP reduction, DH was superior to VC at all time points (P < or = 0.05) and to SC at months 3, 5, 6, 8, and 9 (P < or = 0.03). For DH, the maximum ALG in deep (> or = 7 mm) pockets was 1.7 mm and PDR 2.9 mm compared to 0.8 mm and 1.6 mm, respectively for moderate (5 to 6 mm) pockets. Test articles were applied without anesthesia and no serious adverse events occurred in the trial. The results of this study indicate that 10% doxycycline hyclate delivered in a biodegradable delivery system is an effective means of reducing the clinical signs of adult periodontitis and exhibits a benign safety profile.

Repair following treatment of circumferential periodontal defects in dogs with collagen and expanded polytetrafluoroethylene barrier membranes.

This study was designed to evaluate healing following treatment of periodontal defects using 2 collagen barrier membranes with different degrees of cross-linking, and to compare the results to those following use of an expanded polytetrafluoroethylene (ePTFE) membrane. Horizontal, circumferential defects were created in mandibular premolar teeth of 6 beagle dogs, followed by placement of membranes and wound closure. Postoperative healing was monitored clinically for 6 months, at which time the animals were sacrificed and specimens were taken for histological examination. Clinical observations indicated that the highly cross-linked, slow-resorbing collagen membrane did not integrate with the tissues the way the less crosslinked, rapid-resorbing collagen did. Membrane exposure was typical for the slow-resorbing membrane in contrast to the rapid-resorbing membrane which remained covered. The inferiority of the slow-resorbing membrane was evident by the extensive clinical recession and the attachment level measurements taken at 6 months, and it was decided to omit this membrane from histometric analysis. Histological examination of root surfaces treated with rapid-resorbing collagen or ePTFE membranes revealed substantial reparative healing. The connective tissue repair amounted to 84% of the treated root surface height for the rapid-resorbing collagen and 53% for the ePTFE membrane (difference not statistically significant). However, the connective tissue repair to the rapid-resorbing collagen group root surfaces was often associated with a layer of ankylosis (44%, versus 8% of the ePTFE group). It appeared that much of the ankylotic response was initiated from the furcation area and extended around to the buccal and lingual surfaces. In addition, this study provided histological evidence that granulation tissue forming under clinically exposed and plaque contaminated ePTFE membranes can still result in connective tissue repair. It was concluded that the rapid-resorbing collagen membranes and the ePTFE membranes seem capable of stimulating periodontal connective tissue repair, whereas the slow-resorbing collagen membranes were unsuccessful in this effort, as seen in this dog model.

Does root surface conditioning with citric acid delay healing?

Effects of topical citric acid application on tissue maturation was studied in standardized periodontal defects in 6 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and recessed 0.5 mm into the dentin of maxillary canines. 1 defect in each dog was conditioned with a saturated solution of citric acid for 3 min and then rinsed with saline. Control defects in contralateral teeth were treated with saline only for the same length of time. The defects were covered with an expanded polytetrafluoroethylene membrane and the flaps repositioned and sutured. 14 days postsurgery, healing appeared more advanced along the defect walls and floor than in the center of the defect in all instances. Histometrically, citric acid-conditioned defects exhibited a higher density of collagen fibers along the defect walls and floor and adjacent to the barrier membrane as well as more advanced resolution of the residual blood clot than the surgical controls. Differences in fibroblast density within specimen pairs were non-significant. All control defects but none of the acid-conditioned defects showed an artifactual split between the dentin walls and the granulation tissue. This study failed to support the contention that topical application of citric acid to root surfaces may delay healing following periodontal surgery.

Impaired early bone formation in periodontal fenestration defects in dogs following application of insulin-like growth factor (II). Basic fibroblast growth factor and transforming growth factor beta 1.

Effects of a topically applied growth factor combination on fibroblast migration, collagen fiber formation and bone regeneration were studied in standardized periodontal defects in 4 beagle dogs. Following elevation of facial mucoperiosteal flaps, fenestration defects, 3 mm in diameter, were made through the cortical bone and into the dentin of maxillary and mandibular teeth. Collagen sponges, impregnated with 200 ng insulin-like growth factor II, 20 ng basic fibroblast growth factor and 6 ng transforming growth factor beta 1 were fitted to defects randomly in right or left quadrants and the flaps repositioned and sutured. Contralateral control defects received the collagen with vehicle only. Experimental procedures were staggered to allow observations of healing 3, 7, 10, and 14 days after surgery. Histometric analysis showed no differences in fibroblast and collagen density between control and growth factor defects. Bone regeneration was significantly greater in control than in growth factor defects 10 and 14 days after surgery. The rate of healing generally appeared more affected by intra-dog variations or procedural variations than by the growth factor combination.

Influence of tooth instrumentation roughness on subgingival microbial colonization.

This study evaluated microbial colonization of periodontal pockets subjected to root instrumentation with a curet or a rotating diamond. Ten maxillary and 10 mandibular subgingival pockets were established in the canines of 5 beagle dogs. The subgingival root surface areas were debrided by a sharp curet or a flame-shaped, fine-grained, rotating diamond point. The dogs were fed a plaque-inducing diet for 70 days. Specimens from both instrumentation groups were then harvested and prepared for stereomicroscopic and scanning electron microscopic evaluation. Grading of the extent of subgingival colonization was performed in coded specimens directly on the fluorescent screen of the scanning electron microscope in a grid-counting system. Error of the method was assessed by duplicate counts. The subgingival root surface areas were divided into 3 zones: cervical, middle, and apical, and statistical differences between these zones as well as between the 2 instrumentation groups were calculated. The results revealed that curet-treated surfaces were smoother and promoted less subgingival colonization than diamond-treated surfaces. The difference in amount of bacterial colonization between the 2 groups was statistically significant (P < 0.05) in all zones. Bacterial colonization decreased in apical direction in both instrumentation groups. For the diamond-treated specimens, this decrease was significant (P < 0.05) between each of the 3 zones. In the curet-treated specimens, the decrease was significant only between the cervical and the apical zone (P < 0.05). The present study has demonstrated that subgingival instrumentation roughness significantly influences the subgingival microbial colonization.

Periodontal repair in dogs: space provision by reinforced ePTFE membranes enhances bone and cementum regeneration in large supraalveolar defects.

Regeneration of alveolar bone and cementum following reconstructive therapy with reinforced space providing expanded polytetrafluorethylene (ePTFE) membranes was evaluated in supraalveolar mandibular premolar periodontal defects in five beagle dogs. The surgically-created defects in contralateral jaw quadrants were randomly assigned to receive the dome-shaped membrane or serve as surgical control. Flaps were positioned to completely submerge the teeth and sutured. The dogs were sacrificed 8 weeks after surgery and tissue blocks including teeth and surrounding structures processed for histology. Membrane treated defects in two animals became exposed and infected leaving intact quadrants in three dogs for histometric analysis. Parameters evaluated included defect height, height and area of regenerated alveolar bone, height of regenerated cementum, root resorption, and ankylosis. Mean defect height approximated 4.1 mm. Mean height (+/- s.d.) of regenerated alveolar bone amounted to 2.9 +/- 0.6 and 0.6 +/- 0.2 mm for membrane and control defects, respectively (P = 0.006). Corresponding values for bone area were 1.4 +/- 0.7 and 0.4 +/- 0.4 mm2 (P = 0.02). Cementum regeneration was observed in all teeth averaging (+/- s.d.) 1.6 +/- 0.3 mm for membrane treated and 0.1 +/- 0.1 mm for control defects (P = 0.01). Small amounts of root resorption were seen in all teeth with no significant difference between treatments. Ankylosis was noticed in three membrane treated and two control teeth. The present study provides a biologic rationale for space provision for enhanced bone and cementum regeneration in periodontal defects subject to reconstructive therapy.

Periodontal regeneration with bone grafts.

This paper reviews the clinical and histologic results following the use of bone autografts and allografts in periodontal therapy. Results from case reports and controlled clinical trials are discussed. Reports about bone grafts and combination procedures, including coronally positioned flaps and guided tissue regeneration procedures, are also reviewed. Studies analyzing long-term stability of grafts are discussed, as well as tissue banking procedures and safety considerations when freeze-dried bone allografts are used. Tables summarizing the results and methodologies of clinical trials cited are included to provide a method of comparison between the studies. The analysis of results of clinical trials using bone graft materials indicates that there is a consistent pattern of more bone fill in grafted versus nongrafted sites. However, the magnitude of this fill represents only about 60% of the treated defects.

Effect of stannous fluoride and tetracycline on periodontal repair after delayed tooth replantation in dogs.

Previous studies have indicated that inflammatory resorption and ankylosis, which are frequent sequela after delayed tooth replantation, can be greatly reduced by treating the root surface with 1% solutions of stannous fluoride and tetracycline. However, the SnF2 conditioning leaves a long-standing inflammatory reaction in the periodontal ligament. To examine whether a more dilute SnF2 solution would reduce postoperative inflammation without jeopardizing any beneficial effects, anterior teeth in three young adult beagles were extracted and allowed to air-dry for 45 min. They were then immersed in 0.1% SnF2 for 5 min, rinsed in saline, immersed in 1% doxycycline HCl for 5 min, rinsed, and replanted. Control teeth were air-dried and replanted without further treatment. Block biopsies were harvested after 4 wk of healing and processed for histometric analysis. In experimental teeth, 85% of the root surface area showed normal healing, compared to 33% in control teeth. Conversely, resorption and ankylosis were more frequent in controls than in experimental teeth. A persisting inflammatory reaction either adjacent to or at a distance from the root surface was seen in limited areas in both experimental and control teeth. Compared to preceding studies, the findings indicate that reducing the strength of the SnF2 solution from 1% to 0.1% may result in less persistent inflammation, at the cost, however, of less complete prevention of inflammatory resorption and ankylosis.

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)

Collagen linkage in periodontal connective tissue reattachment. An ultrastructural study in beagle dogs.

Early stages of connective tissue reattachment to surgically denuded cementum and root dentin following citric acid application were studied in fenestration wounds. Block specimens were obtained after seven, 14, and 21 days. Continuity between newly deposited collagen fibrils in the granulation tissue and unmasked dental matrix collagen had been established within seven days by interdigitation of fibrils in an up to 0.5 micron-wide zone at the cementum or dentin surface. Splicing of collagen at the fibrillar level by direct attachment to the severed end of matrix fibrils or by juxtapositioning of new and old fibrils was seen in rare instances only. At 14 and 21 days, distinct bundles of collagen fibrils inserted deeply into the orifice of dentinal tubules. Arrested and reversed surface resorption was encountered at all time points. At these sites as well, new collagen fibrils interdigitated with denuded matrix collagen, while some resorbed surfaces were characterized by absence of collagen continuity. The results lend continued support to the concept of reattachment based on interdigitation of collagen fibrils. However, since attachment is established even in the absence of this feature, a significant role for specific attachment substances not shown can also be postulated.