Effect of topical application of doxycycline on pulp revascularization and periodontal healing in reimplanted monkey incisors.

Maxillary incisors in 47 monkeys, 54 in the experimental group (I) and 117 in the control group (II), were extracted and reimplanted, either immediately or after 30 or 60 min wet or dry storage. Incisors in the experimental group I were additionally kept 5 min in a suspension of 1 mg doxycycline in 20 ml physiologic saline, freshly prepared for each of the 15 animals before reimplantation. The observation time varied from 6 to 8 weeks. The teeth were removed in tissue blocks, histologically processed and evaluated for occurrence of complete pulp revascularization (CPR), presence of the micro-organisms in the pulpal lumen and ankylosis or inflammatory root resorption. Then the results were statistically evaluated, using log-linear analyses and chi-square tests (SAS, 1985) for the comparisons between group I and group II. These analyses revealed that topical application of doxycycline increased the frequency of complete pulp revascularization (P less than 0.002) and decreased the frequency of micro-organisms in the pulpal lumen (P less than 0.001). Furthermore, the frequencies of ankylosis (P less than 0.05) and inflammatory root resorption (P less than 0.001) were also decreased compared with the control group of teeth. It was concluded that the effect of topical treatment with doxycycline was most probably exerted on the micro-organisms that contaminated root surface during the extra-alveolar time; contamination of necrotic pulp tissue from the mechanical damage in the cervical part of the root surface was not affected.     

Pulp revascularization in reimplanted immature monkey incisors – predictability and the effect of antibiotic systemic prophylaxis

Abstract In 32 monkeys 105 immature maxillary incisors were extracted and reimplanted either immediately or after 30 or 60 min wet or dry storage. Of the monkeys, 17 (group I) did not receive and 15 (group II) received prophylactic treatment with 4 mg/kg doxycycline before extraction and 2 mg/kg for 5 d after reimplantation. The observation time varied from 6 to 8 weeks. After being histologically processed, the material was evaluated with respect to the amount of vital tissue and presence of microorganisms in the pulpal lumen. A comparison revealed no difference in the results between the groups. The results were therefore pooled and statistically analysed with respect to the significance of apical foramen width, extra-alveolar time, wet or dry storage and presence of micro-organisms in the pulpal lumen for the occurrence of complete pulp revascularization (CPR). The overall frequency of CPR was 18%. Log-linear analyses (SAS, 1985) of the material as a whole or of separate parameters consistently revealed a relationship between presence of microorganisms and absence of CPR (P= 0.0001). A higher frequency of CPR and a lower frequency of micro-organisms (P= 0.05) was found only for the group of immediately reimplanted teeth. The presence of micro-organisms could be explained for 61 teeth. In 27 of these, blood clots containing bacteria in the apical portion of pulpal lumen indicated contamination during the extra-alveolar time, while in 34, the micro-organisms originated from plaque covered mechanical damage in the cervical part of the root surface.     

Rate and predictability of pulp revascularization in therapeutically reimplanted permanent incisors

Abstract The aim of the present investigation was to study the frequency of pulp revascularization in therapeutically reimplanted incisors as well; is its relationship with the following factors: width of apical foramen, duration of extra-alveolar lime, storage conditions and postoperative administration of antibiotics. Out of 72 immature teeth (width of apical foramen 1.1–5.0 mm) the pulp was revascularized in 13 (18%), while in 88 mature teeth (width of apical foramen 1.0 mm or less) no revascularization occurred. Among parameters tested statistically in immature teeth, a significantly increased frequency of revascularization (p < 0.05) was only found in teeth reimplanted within 45 minutes after avulsion, when compared with teeth reimplanted after a longer extra-alveolar time, and in mandibular incisors when compared with maxillary incisors (p < 0.01). All teeth in which revascularization did not occur exhibited a periapical radiolucency and/or external inflammatory root resorption.     

Supportive periodontal therapy of furcation sites: non-surgical instrumentation with or without topical doxycycline

Objectives: Evaluation of the clinical effect of topical subgingival application of doxycycline gel adjunctively to scaling and root planing (SRP) at furcation sites during supportive periodontal therapy (SPT).
Material and Methods: In 39 SPT patients exhibiting at least four pockets 5 mm with bleeding on probing, SRP was rendered in all pockets 4 mm. Additionally, 14% doxycycline gel was applied subgingivally in 20 patients after random assignment (SRP&DOXY). Clinical parameters were assessed at baseline, 3, 6, and 12 months after therapy. Additional benefit of topical doxycycline was evaluated as a short-term (3 months) improvement of furcation involvement and influence on the frequency of re-instrumentation up to 12 months.
Results: A total of 323 furcation sites (class 0: 160; class I: 101; class II: 18; and class III: 44) were treated (SRP: 165, SRP&DOXY: 158). SRP&DOXY resulted in better improvement of furcation involvement than SRP alone 3 months after treatment ( p =0.041). However, SRP&DOXY failed to show a significant difference between both groups in the number of re-instrumentations.
Conclusion: Single subgingival application of doxycycline in addition to SRP had a short-term effect on furcation involvement. However, it failed to reduce the frequency of re-instrumentation up to 12 months at furcation sites.     

Surgical treatment of ankylosed and infrapositioned reimplanted incisors in adolescents

Abstract – A method for preserving the alveolar ridge of ankylosed and infrapositioned incisors and improving conditions for a subsequent prosthetic therapy is described and evaluated clinically and radiographically. The method involves removal of the crown and root filling from the root, which is retained and covered with a mucoperiosteal flap. Clinically, there were no postoperative complications and after the follow-up a satisfactory prosthetic restoration was performed in all cases, regardless of the degree of infraposition before treatment. Radiographically, no pathologic changes were observed apart from a continuous resorption and replacement of lost root substance by bone. Alveolar bone level shifted only slightly between postoperative and 12-month follow-up radiographs, in a majority of cases in a coronal direction.     

Non-surgical periodontal therapy with adjunctive topical doxycycline: a double-blind randomized controlled multicenter study

AIM: Evaluation of the clinical effect of topical application of doxycycline adjunctive to non-surgical periodontal therapy. METHODS: A total of 111 patients suffering from untreated or recurrent moderate to severe periodontitis at 3 different centers (Heidelberg, Frankfurt, Nijmegen) were treated in this double-blind split-mouth study. In each patient, 3 different treatment modalities were assigned randomly to 3 test teeth: scaling and root planing alone (SRP), SRP with subgingival vehicle control (VEH), and SRP with subgingival application of a newly developed biodegradable 15% doxycycline gel (DOXI). At baseline, clinical parameters were measured at all single rooted teeth using a reference splint: PlI, PPD, relative attachment level (RAL-V), GI. 3 strata were generated according to baseline PPD: (i) 5-6 mm, (ii) 7-8 mm, (iii) > or =9 mm. Not more than 50% active smokers were allowed to each stratum. 3 and 6 months after therapy re-examination was performed by examiners blinded to baseline data and test sites. The statistical comparison of RAL-V gain and PPD reduction between the treatments was based on a repeated measures ANOVA with correction according to Huynh & Feldt. The comparison of SRP versus DOXI was considered as the main study question. RESULTS: 110 patients finished the 3 months and 108 the 6 months examination. The study did not show adverse effects of VEH or DOXI except for one singular inflammation that occurred 2 months after application of the doxycycline gel. DOXI provided statistically significantly more favorable PPD reduction (SRP: -2.4+/-1.4 mm, VEH: -2.7+/-1.6 mm, DOXI: -3.1+/-1.2 mm; SRP versus DOXI p=0.0001, VEH versus DOXI p=0.0066) and RAL-V gain (SRP: 1.6+/-1.9 mm, VEH: 1.6+/-2.2 mm, DOXI: 2.0+/-1.7 mm; SRP versus DOXI p=0.027, VEH versus DOXI p=0.038) than SRP and VEH after 6 months. CONCLUSIONS: Adjunctive topical subgingival application of a biodegradable 15% doxycycline gel was safe and provided more favorable RAL-V gain and PPD reduction than SRP alone and VEH. Thus, by use of topical doxycycline the threshold for surgical periodontal therapy might be moved toward deeper pockets.     

Locally delivered doxycycline improves the healing following non-surgical periodontal therapy in smokers

OBJECTIVE: The outcome of non-surgical periodontal therapy is known to be inferior in smokers compared to non-smokers. In the present study, the question was asked whether such a difference in healing response may be less evident following adjunctive use of locally delivered controlled-release doxycycline. METHODS: One hundred and three patients (42 smokers, 61 non-smokers), each having at least eight periodontal sites with PPD (probing pocket depth) > or =5 mm, were following stratification for smoking randomly assigned to two different treatment protocols; non-surgical scaling/root planing (Control) or ultrasonic instrumentation+application of a 8.5% w/w doxycycline gel (Atridox trade mark ) (Test). Instructions in oral hygiene were given to all patients. Clinical examinations of plaque, PPD, clinical attachment level (CAL) and bleeding following pocket probing were performed at baseline and after 3 months. Primary efficacy endpoints were changes in PPD and CAL. Patient mean values were calculated as basis for statistical analysis (multiple regression analyses). RESULTS: The baseline examination revealed no significant difference in mean PPD between treatment groups or between smokers and non-smokers (mean PPD 5.7-5.9 mm). The mean PPD reduction in the control group at 3-month was 1.1 mm (SD=0.45) for smokers and 1.5 mm (0.67) for non-smokers. In the test group the PPD reduction was 1.4 mm (0.60) and 1.6 mm (0.45) for smokers and non-smokers, respectively. The mean CAL gain for smokers and non-smokers amounted to 0.5 mm (0.56) and 0.8 mm (0.71), respectively, in the control group, and to 0.8 mm (0.72) and 0.9 mm (0.82), respectively, in the test group. Multiple regression analysis revealed that smoking and initial PPD negatively influenced the treatment outcome in terms of PPD reduction and CAL gain, while the use of doxycycline had a significant positive effect. CONCLUSION: Locally applied controlled-release doxycycline gel may partly counteract the negative effect of smoking on periodontal healing following non-surgical therapy.     

Effect of root surface alterations on periodontal healing.

Abstract A companion study reported that new connective tissue attachment did not occur to a surgically denuded root surface when transplanted into a normal periodontium. It was the purpose of this study to evaluate periodontal healing adjacent to a citric acid treated denuded root surface. In four squirrel monkeys, 12 teeth were extracted and reimplanted after surgical denudation and citric acid conditioning of the coronal root surface. The study design provided three teeth for histologic analysis at 1, 3, 7 and 21 days after reimplantation. One and 3 days after reimplantation a zone of fibrin containing inflammatory cells and erythrocytes was interposed between the root surface and remaining periodontal fibers. The fibrin network appeared to be attached to the root surface by arcade-like formations. The apical termination of the epithelium was located at the coronal extent of the fibrin zone. Granulation tissue and new fibers were aggregating along and perpendicular to the root surface at 7 days; and new connective tissue attachment had been established at 21 days. Extensive root resorption was present along the intra-alveolar part of the root surface. Epithelium had not migrated apically along the denuded root surfaces. The results indicated that citric acid treatment of denuded root surfaces resulted in new connective tissue attachment, and the response appeared to be dependent upon early establishment of fibrin linkage with the root surface.     

Pulp revascularization of replanted immature dog teeth after treatment with minocycline and doxycycline assessed by laser Doppler flowmetry, radiography, and histology

Abstract –  This study investigated the effect of topical antibiotic treatment on pulp revascularization in replanted teeth. Thirty-four immature teeth were selected from three young dogs. Baseline radiographs and laser Doppler flowmetry (LDF) readings were obtained. Specimens were randomly divided into four groups: Thirty-eight teeth were extracted, kept dry for 5 min, and either (Group 1) covered with minocycline mixture (G1, n  = 11), (Group 2) soaked in doxycycline (G2, n  = 11), or (Group 3) soaked in saline (G3-negative control, n  = 6), and replanted. Teeth in Group 4 were not extracted (positive control, n  = 6). Postoperative radiographs and LDF readings were obtained for 2 months after replantation. After sacrifice, the jaws were collected and processed for light microscopy. Pre- and postreplantation LDF readings and radiographs, and histologic findings were analyzed to assess revascularization. Pulp revascularization occurred in 91% (G1), 73% (G2), and 33% (G3) of the specimens. In conclusion, minocycline facilitates pulp revascularization in replanted immature teeth after replantation.     

Effect of root surface alterations on periodontal healing. I. Surgical denudation

Abstract The present study was undertaken to evaluate the effect of root surface denudation on periodontal healing. Twelve teeth, distributed in four squirrel monkeys, were extracted and reimplanted after surgically denuding the coronal root surface of connective tissue fibers and cementum by root planing. The reimplantation schedule provided three teeth for histologic analysis at 1, 3, 7 and 21 days after reimplantation. One day after reimplantation a zone of fibrin enmeshing erythrocytes and inflammatory cells was interposed between the root surface and the remaining periodontal fibers attached to the alveolar bone. Epithelium migrated rapidly along the denuded root, had reached the alveolar crest at 3 days, and was within the ligament space at 7 days. At 21 days, the epithelium was at the apical limit of root instrumentation, which corresponded to the level of attached connective tissue fibers on the root surface. No evidence of new connective tissue attachment was observed on the denuded root surface. It was concluded that the absence of fibers on the root surface resulted in apical migration of the epithelium, and precluded formation of new connective tissue attachment.     

Effect of non-surgical periodontal treatment with or without doxycycline on the periodontium of type 1 diabetic patients

AIM: The present investigation was performed to study how type 1 diabetics responded to non-surgical periodontal treatment with and without adjunctive doxycycline. METHOD: Sixty diabetic type 1 patients (mean age 35.3+/-9 years) with moderate-to-severe periodontal disease were selected and divided into two groups of 30 patients each. Both groups were sex and age matched and had similar amounts of periodontal destruction. Plaque index (PI), bleeding on probing (BOP), probing depth (PD) and clinical attachment levels (CAL) were recorded. Group 1 (30 patients) was treated with oral hygiene instruction, scaling and root planing, chlorhexidine rinses twice a day and doxycycline (100 mg/day for 15 days). Group 2 (30 patients) had the same treatment but without doxycycline. After 12 weeks their periodontal condition was reevaluated. RESULTS: After treatment, both groups had a significant improvement in all periodontal parameters, since PI, BOP, probing pocket depth (PPD) and CAL were significantly reduced. However, the reduction in PD in pockets > or =6 mm and in BOP were more evident when doxycycline was used (group 1). Differences between groups for these parameters were statistically significant (p=0.03). CONCLUSION: Although both periodontal treatment regimens are effective in type 1 diabetics, the use of doxycycline as an adjunct, provided more significant results when good plaque control was achieved.     

Systemic doxycycline administration in the treatment of periodontal infections (I). Effect on the subgingival microbiota

Systemic doxycycline is one of the more common antimicrobial agents used in the treatment of periodontal infections and yet little is known of its effect on subgingival plaque composition during and after its administration. The purpose of the present investigation was to evaluate changes in subgingival plaque composition during and after 14 days of doxycycline administration. 20 subjects with adult periodontitis were randomly assigned to test (n = 10) and control (n = 10) groups. The subjects received full mouth clinical assessment of pocket depth, attachment level, BOP, gingival redness, suppuration and plaque accumulation at baseline and 90 days. All subjects received full mouth SRP at baseline and, additionally, the test group received 100 mg doxycycline daily for 14 days. Subgingival plaque samples were taken from the mesial surface of up to 28 teeth in each subject at baseline and 90 days. In addition, plaque samples were taken from 2 randomly selected teeth at 3, 7 and 14 days during and after antibiotic administration. Control subjects were sampled at the same time points. Counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization and fluorescent detection. Significance of differences between test and control groups was determined at each time point using the Mann Whitney test. Significance of changes over time within test and control groups was determined using the Quade test. A modest but significant reduction in mean pocket depth from baseline to 90 days occurred in both test and control groups. A significant decrease in the % of sites with gingival redness occurred in the test group. There were no significant differences in proportions between test and control groups for 33 of the test species at any time point. Test subjects exhibited lower proportions of 4 Actinomyces species and an increase in 3 Streptococcus species during antibiotic administration. After cessation of doxycycline, Actinomyces sp. increased while Streptococcus sp. returned to baseline proportions. The relationship between these 2 genera appeared to be reciprocal; an increase in one was accompanied by a decrease in the other. Periodontal pathogens including B. forsythus, P. gingivalis, T. denticola and A. actinomycetemcomitans were not significantly altered by oral administration of doxycycline using conventional therapeutic dosage.     

Effect of drying on viability of periodontal membrane

abstract – The influence of a dry extra-alveolar period on the viability of cells in the periodontal membrane of human and monkey teeth was examined in vitro . Extracted mature teeth were allowed to dry for 0, 30, 60, 90, and 120 min. Cell viability was examined with the following methods: 1) Culturing the teeth with subsequent trypsination and counting of viable cells. 2) Culturing the teeth with subsequent vital staining of the root surface with neutral red and estimation of the vital stained periodontal membrane area in percentage of the total root surface. Both methods revealed that the number of viable cells in the period declines very rapidly with an increase in drying time. After 2 h it was not possible to demonstrate cell viability using tissue culture technique.     

血管再生治疗犬年轻恒牙根尖周炎的实验研究

目的：比较血管再生和根尖诱导成形术治疗犬年轻恒牙根尖周炎的效果。方法：选用3只5-6个月犬的30颗双根前磨牙,建立根尖周炎模型,三联抗生素糊剂消毒后,随机分为三组,即血管再生组、根尖诱导组和空白对照组。于术后4周、8周、12周分别拍摄X线片,比较根尖愈合情况。术后12周处死动物,常规制作组织切片,观察管腔内再生组织的成分以及根尖硬组织形成情况。结果：①X线观察：三组均可看到根尖闭合影像,两实验组的根尖闭合率优于对照组（P〈0．05）,实验组之间差异无统计学意义（P〉0．05）。②组织形态学观察：血管再生组和对照组有类似于牙骨质样组织（管内牙骨质）从根尖孔向内延伸,在管壁沉积,管腔内出现骨样组织（管内骨组织）,共同促使牙根伸长和管壁增厚,且血管再生组的两种组织发生率优于对照组（P〈0．05）,根尖诱导组未见此两种组织。结论：血管再生在管壁增厚和牙根伸长等方面优于根尖诱导成形术。     

Comparison of plaque accumulation after topical application and mouth rinsing with chlorhexidine gluconate

This study measured plaque accumulation on anterior teeth after topical or mouth rinse application of 0.2% chlorhexidine gluconate. Compared with water plaque scores were highly significantly reduced. There was no significant difference in plaque scores between topical application or mouth rinsing. The importance of locally adsorbed chlorhexidine is emphasised and the relevance of an oral reservoir effect questioned.     

Pulp revascularization in reimplanted immature monkey incisors--predictability and the effect of antibiotic systemic prophylaxis.

In 32 monkeys 105 immature maxillary incisors were extracted and reimplanted either immediately or after 30 or 60 min wet or dry storage. Of the monkeys, 17 (group I) did not receive and 15 (group II) received prophylactic treatment with 4 mg/kg doxycycline before extraction and 2 mg/kg for 5 d after reimplantation. The observation time varied from 6 to 8 weeks. After being histologically processed, the material was evaluated with respect to the amount of vital tissue and presence of micro-organisms in the pulpal lumen. A comparison revealed no difference in the results between the groups. The results were therefore pooled and statistically analysed with respect to the significance of apical foramen width, extra-alveolar time, wet or dry storage and presence of micro-organisms in the pulpal lumen for the occurrence of complete pulp revascularization (CPR). The overall frequency of CPR was 18%. Log-linear analyses (SAS, 1985) of the material as a whole or of separate parameters consistently revealed a relationship between presence of micro-organisms and absence of CPR (P = 0.0001). A higher frequency of CPR and a lower frequency of micro-organisms (P = 0.05) was found only for the group of immediately reimplanted teeth. The presence of micro-organisms could be explained for 61 teeth. In 27 of these, blood clots containing bacteria in the apical portion of pulpal lumen indicated contamination during the extra-alveolar time, while in 34, the micro-organisms originated from plaque covered mechanical damage in the cervical part of the root surface.