Cristiano Susin

Publications of Cristiano Susin

• Oral health status in elders from South Brazil: a population-based study.

  Authors: Eduardo J Gaio, Alex N Haas, Vinícius C Carrard, Rui V Oppermann, Jasim Albandar, Cristiano Susin

  Gerodontology. 04/2012;

  Gerodontology 2012; doi: 10.1111/j.1741-2358.2011.00617.x Oral health status in elders from South Brazil: a population-based study Objective:  To assess the oral health status of community-dwellingGerodontology 2012; doi: 10.1111/j.1741-2358.2011.00617.x Oral health status in elders from South Brazil: a population-based study Objective:  To assess the oral health status of community-dwelling adults aged 60 years and older from southern Brazil and to determine demographics, socioeconomic, behavioural and dental risk indicators. Materials and methods:  This cross-sectional study used a multistage, probability sampling method to draw a representative sample of the metropolitan area of Porto Alegre, Brazil. A subsample of 217 subjects was included in this analysis. Oral mucosal lesions, dental caries, tooth loss and periodontal status (full-mouth, six sites per tooth exam) were assessed by calibrated examiners. Results:  Prevalence of edentulism was 39.5%, and mean tooth loss was 20.2 (SE = 0.6). Older individuals [Odds Ratio (OR) = 2.2], women (OR = 2.3), white people (OR = 5.9), individuals of lower socioeconomic status (OR = 5.6) and smokers (OR = 3.5) had higher likelihood of being edentulous. Approximately 36% of dentate individuals had caries and/or restoration affecting, in average, 5.0 teeth. Periodontitis affected 79% of subjects, and it was associated with older age (OR = 4.0), men (OR = 3.4) and large amounts of supragingival plaque (OR = 3.0). Conclusion:  Poor oral health was observed in this elderly population from South Brazil. Sociodemographic disparities accounted for most of the burden of disease and treatment needs.

• Relationship between cytokine levels in serum and gingival crevicular fluid (GCF) in pregnant women.

  Authors: Tiago Fiorini, Priscila Vianna, Patricia Weidlich, Marta Liliana Musskopf, Carlos Heitor Cunha Moreira, José Artur Bogo Chies, Cassiano Kuchenbecker Rösing, Rui Vicente Oppermann, Cristiano Susin

  Cytokine. 04/2012; 58(1):34-9.

  Periodontal disease has been linked to systemic diseases/disorders and a low-grade systemic inflammatory status originated from periodontitis has been proposed as a possible explanation for thisPeriodontal disease has been linked to systemic diseases/disorders and a low-grade systemic inflammatory status originated from periodontitis has been proposed as a possible explanation for this association. This study evaluates the relationship, early in pregnancy, between gingival crevicular fluid (GCF) and serum levels of a panel of cytokines that have been implicated in PTB and periodontal disease. One hundred pregnant women aged 18-35years old with a gestational age up to 20weeks were included (mean±SD gestational age:16.1±3.5weeks). Four periodontal sites per subject were randomly selected for GCF collection. Serum and GCF levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were analyzed using a cytometric bead array. Regression and correlation analyses were used to assess the relationship between serum and GCF cytokine levels. Participants had widespread periodontal inflammation but limited periodontal destruction. Cytokine levels were significantly higher in GCF than serum for all cytokines but IL-10. GCF levels had small but significant effect on serum levels for IL-10 (β=0.34±0.09, p<0.01), IL-12p70 (β=0.48±0.08, p<0.01) and TNF-α (β=0.29±0.09, p<0.01). Periodontal probing depth and bleeding on probing were significantly associated with GCF levels for IL-1β, IL-6 and IL-8; however, they had negligible effect on serum cytokine levels. Correlation between GCF and serum levels was non-significant, except for IL-12p70, which showed a significant but small correlation between the two sources (r=0.32, p=0.001). GCF cytokine levels were not strongly associated with serum cytokine levels in pregnant women with widespread periodontal inflammation but limited periodontal destruction.

• Adjunctive Azithromycin in the Treatment of Aggressive Periodontitis: Microbiological Findings of a 12-Month Randomized Clinical Trial.

  Authors: Alex Nogueira Haas, Carina Maciel Silva-Boghossian, Ana Paula Colombo, Cristiano Susin, Jasim M Albandar, Rui Vicente Oppermann, Cassiano Kuchenbecker Rösing

  Journal of dentistry. 03/2012;

  OBJECTIVES: To compare the subgingival microbiological outcomes of azithromycin or placebo as adjuncts to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP), and toOBJECTIVES: To compare the subgingival microbiological outcomes of azithromycin or placebo as adjuncts to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP), and to secondarily evaluate the microbiological effect of supragingival scaling in AgP patients. METHODS: Twenty-four AgP subjects 13-26 years of age received a 15-day program of supragingival scaling (SC) and were then randomly assigned to SRP with systemic azithromycin or placebo. Subgingival samples were taken with sterile paper points at baseline, 15 days after SC, and at 3, 6 and 12 months following SRP. Microbiological analysis was performed by the checkerboard DNA-DNA hybridization. RESULTS: Changes in bacterial levels from baseline to 15 days after SC were similar in the 2 groups. When subjects were analyzed as a single group, significant reductions after SC were observed for A. gerencseriae, C. ochracea, and T. denticola. During the 12-month follow-up, levels of most of the bacteria decreased in both groups in a similar pattern. For instance, A. israelli, V. parvula, S. gordonii, C. ochracea, E. corrodens, E. nodatum, F. periodonticum and F. nuc. polymorphum decreased significantly within the groups. CONCLUSIONS: Azithromycin was ineffective in lowering the subgingival levels of important putative periodontal pathogens in young AgP subjects compared to placebo. Clinical significance: Scaling and root planing with adjunctive systemic azithromycin provides little additional benefit compared to placebo in reductions of major subgingival periodontal pathogens.

• Effect of nonsurgical periodontal therapy and strict plaque control on preterm/low birth weight: a randomized controlled clinical trial.

  Authors: Patricia Weidlich, Carlos Heitor C Moreira, Tiago Fiorini, Marta L Musskopf, José M da Rocha, Maria Lucia R Oppermann, Anne M Aass, Per Gjermo, Cristiano Susin, Cassiano K Rösing, Rui V Oppermann

  Clinical oral investigations. 01/2012;

  OBJECTIVE: This randomized controlled clinical trial was carried out to assess the effect of comprehensive nonsurgical periodontal treatment and strict plaque control performed during pregnancy onOBJECTIVE: This randomized controlled clinical trial was carried out to assess the effect of comprehensive nonsurgical periodontal treatment and strict plaque control performed during pregnancy on the reduction of preterm and/or low birth weight rates (PTLBW). MATERIAL AND METHODS: Three hundred and three women were randomly allocated to receive periodontal treatment either during pregnancy (n = 147, test group) or after delivery (n = 156, control group). During pregnancy, the control group received only one session of supragingival scaling and oral hygiene instruction. In contrast, the test group received comprehensive periodontal treatment including multiple sessions of scaling and root planing, oral hygiene instructions, and frequent maintenance visits. RESULTS: At baseline, periodontal inflammation was observed in approximately 50% of sites and attachment loss affected <15% of sites. Compared to controls, women in the test group had significant reductions in the percentage of sites with plaque (48.5% vs. 10.3%, p < 0.001), gingival bleeding (23.3% vs. 2.5%, p < 0.001), calculus (21.3% vs. 4.1%, p < 0.001), bleeding on probing (38.1% vs. 2.6%, p < 0.001) and probing depth ≥3 mm (19.97% vs. -2.45%, p < 0.001). No significant differences were observed between the groups in the occurrence of PT (11.7% vs. 9.1%, p = 0.57), LBW (5.6 % vs. 4.1%, p = 0.59), and PTLBW (4.15% vs. 2.60%, p = 0.53). CONCLUSIONS: Comprehensive periodontal treatment and strict plaque control significantly improved periodontal health; however, no reduction of PTLBW rates was observed. Thus, remaining periodontal inflammation posttreatment cannot explain the lack of effect of periodontal treatment on PTLBW. CLINICAL RELEVANCE: This study demonstrated that periodontal diseases may be successfully treated during pregnancy. Our results do not support a potential beneficial effect of periodontal treatment on PTLBW.

• Sinus augmentation using rhBMP-2/ACS in a mini-pig model: relative efficacy of autogenous fresh particulate iliac bone grafts.

  Authors: Jaebum Lee, Cristiano Susin, Nancy A Rodriguez, Jamie de Stefano, Hari S Prasad, Amanda N Buxton, Ulf M E Wikesjö

  Clinical oral implants research. 01/2012;

  BACKGROUND: Implant dentistry in the posterior maxilla often requires bone augmentation. The gold standard, autogenous bone graft, requires additional surgery with associated morbidity, while boneBACKGROUND: Implant dentistry in the posterior maxilla often requires bone augmentation. The gold standard, autogenous bone graft, requires additional surgery with associated morbidity, while bone biomaterials may not support relevant bone formation. Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS), however, induces significant, clinically relevant bone formation in several settings including the maxillary sinus floor. OBJECTIVE: The objective of this study was to compare local bone formation and osseointegration following maxillary sinus augmentation using rhBMP-2/ACS or a particulate autogenous cancellous bone graft obtained from the iliac crest in conjunction with immediate placement of dental implants. MATERIALS AND METHODS: Bilateral sinus augmentation using an extraoral approach including rhBMP-2 (0.43 mg/ml)/ACS or the autogenous bone graft, alternated between left and right sinus cavities in five adult male Yucatan mini-pigs, was performed. Two 12-mm dental implants were inserted into the sinus wall protruding approximately 8 mm into the sinus cavity. Surgical sites were closed and sutured in layers; block biopsies collected for histometric analysis at 8 weeks. RESULTS: rhBMP-2/ACS induced bone of significantly greater and consistent quality compared with the iliac crest autogenous bone graft; bone density averaging 51.9 ± 3.0% vs. 32.9 ± 2.5% (P = 0.01). However, there were only numerical differences in augmented bone height (9.3 ± 0.5 vs. 8.6 ± 0.7 mm) and bone-implant contact (37.4 ± 3.0% vs. 30.7 ± 5.9%) between treatments. CONCLUSION: rhBMP-2/ACS induces bone of superior quality compared with an iliac crest particulate autogenous cancellous bone graft when used for maxillary sinus augmentation, and should perhaps be considered the new standard for this indication.

• Pattern and rate of progression of periodontal attachment loss in an urban population of South Brazil: a 5-years population-based prospective study.

  Authors: Alex Nogueira Haas, Eduardo José Gaio, Rui Vicente Oppermann, Cassiano Kuchenbecker Rösing, Jasim M Albandar, Cristiano Susin

  Journal of clinical periodontology. 11/2011; 39(1):1-9.

  The aim of this 5-years longitudinal study was to investigate the pattern and rate of periodontal attachment loss (PAL) progression in an urban population in South Brazil. In 2001, a multistageThe aim of this 5-years longitudinal study was to investigate the pattern and rate of periodontal attachment loss (PAL) progression in an urban population in South Brazil. In 2001, a multistage probability sampling strategy was used to derive a representative sample of 1,465 dentate individuals from Porto Alegre, Brazil. Five years later, 697 dentate individuals (294M/403F, mean age: 37.9 ± 13.3) were available for follow-up. PAL was assessed by calibrated examiners using a full-mouth protocol. Estimates of proximal PAL progression and standard errors (SE) are reported. Fifty-six per cent (SE: 1.9) and 36% (SE: 1.8) of subjects showed PAL progression ≥3 mm affecting ≥2 and ≥4 teeth respectively. PAL progression ≥3 mm was mostly localized affecting 3.8 (SE: 0.2) teeth and 5.7 (SE: 0.3) sites. Annual PAL progression was, on average, 0.3 mm (SE: 0.01). Significant differences in PAL progression were observed according to age, gender, race and socioeconomic status. PAL progression increased with age reaching the highest progression rate in the 40-49 years cohort, and then decreased in older age groups. PAL progression was consistently higher among males and non-Whites than females and whites. A large proportion of this urban Brazilian sample was affected by PAL progression underscoring the need for health promotion initiatives aiming at preventing progression of destructive periodontal disease.

• Prevalence and risk indicators for chronic periodontitis in adolescents and young adults in south Brazil.

  Authors: Cristiano Susin, Alex N Haas, Patricia M Valle, Rui V Oppermann, Jasim M Albandar

  Journal of clinical periodontology. 02/2011; 38(4):326-33.

  To describe the distribution of clinical attachment loss (CAL) and to study risk indicators for chronic periodontitis in a large population-based sample of adolescents and young adults from southTo describe the distribution of clinical attachment loss (CAL) and to study risk indicators for chronic periodontitis in a large population-based sample of adolescents and young adults from south Brazil. This cross-sectional study used a subset of data from a larger survey representative of Porto Alegre, Brazil. The sample consisted of 612 individuals (291 males/321 females) aged 14-29 years. Full-mouth, six sites per tooth clinical examinations were performed by calibrated periodontists. Chronic periodontitis was defined as CAL 3mm affecting two or more teeth. Aggressive periodontitis cases were excluded from the analysis. CAL 3 and 5mm affected 50.4% and 17.4% of subjects and 9.7% and 1.1% of teeth, respectively. Prevalence of chronic periodontitis ranged between 18.2% and 72.0% among subjects 14-19 and 24-29 years old, respectively. In the multivariable logistic regression analysis, older age [odds ratio (OR)=2.6, 95% confidence interval (CI)=1.7-3.9 and OR=7.2, 95% CI=3.7-14.0 for 20-24 and 25-29 years old, respectively], low socioeconomic status (OR=1.9, 95% CI=1.4-2.7), heavy smoking (OR=1.7, 95% CI=1.1-2.7) and larger amounts of calculus (OR=2.0, 95% CI=1.2-3.2) were significantly associated with chronic periodontitis. This population of adolescents and young adults had a high prevalence of chronic periodontitis, and its presence was associated with age, socioeconomic status, smoking and calculus.

• Evaluation of implants coated with recombinant human bone morphogenetic protein-2 and vacuum-dried using the critical-size supraalveolar peri-implant defect model in dogs.

  Authors: John F Decker, Jaebum Lee, Carlo Alberto Cortella, Giuseppe Polimeni, Michael D Rohrer, John M Wozney, Jan Hall, Cristiano Susin, Ulf M E Wikesjö

  Journal of periodontology. 12/2010; 81(12):1839-49.

  Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling.Endosseous implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) in a laboratory bench setting and air-dried induce relevant bone formation but also resident bone remodeling. Thus, the objective of this study is to evaluate the effect of implants fully or partially coated with rhBMP-2 and vacuum-dried using an industrial process on local bone formation and resident bone remodeling. Twelve male adult Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load, six animals), or by immersion of the entire implant in a rhBMP-2 solution (soak-load, six animals) for a total of 30 μg rhBMP-2 per implant. All implants were vacuum-dried. The animals were sacrificed at 8 weeks for histometric evaluation. Clinical healing was unremarkable. Bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (± SE) 3.2 ± 0.5 versus 3.6 ± 0.3 mm, and 2.3 ± 0.5 versus 2.6 ± 0.8 mm(2) for coronal-load and soak-load implants, respectively (P >0.05). The corresponding bone density and bone-implant contact registrations averaged 46.7% ± 5.8% versus 31.6% ± 4.4%, and 28% ± 5.6% versus 36.9% ± 3.4% (P >0.05). In contrast, resident bone remodeling was significantly influenced by the rhBMP-2 application protocol. Peri-implant bone density averaged 72.2% ± 2.1% for coronal-load versus 60.6% ± 4.7% for soak-load implants (P <0.05); the corresponding bone-implant contact averaged 70.7% ± 6.1% versus 47.2% ± 6.0% (P <0.05). Local application of rhBMP-2 and vacuum-drying using industrial process seems to be a viable technology to manufacture implants that support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodeling without compromising local bone formation.

• Alveolar ridge augmentation using implants coated with recombinant human growth/differentiation factor-5: histologic observations.

  Authors: Giuseppe Polimeni, Ulf M E Wikesjö, Cristiano Susin, Mohammed Qahash, Richard H Shanaman, Hari S Prasad, Michael D Rohrer, Jan Hall

  Journal of clinical periodontology. 08/2010; 37(8):759-68.

  In vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinantIn vitro and in vivo preclinical studies suggest that growth/differentiation factor-5 (GDF-5) may induce local bone formation. The objective of this study was to evaluate the potential of recombinant human GDF-5 (rhGDF-5) coated onto an oral implant with a purpose-designed titanium porous oxide surface to stimulate local bone formation including osseointegration and vertical augmentation of the alveolar ridge. Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in 12 young adult Hound Labrador mongrel dogs. Six animals received implants coated with 30 or 60 microg rhGDF-5, and six animals received implants coated with 120 microg rhGDF-5 or left uncoated (control). Treatments were alternated between jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at weeks 3, 4, 7, and 8 post-surgery when they were euthanized for histologic evaluation. The clinical examination showed no noteworthy differences between implants coated with rhGDF-5. The cover screw and implant body were visible/palpable through the alveolar mucosa for both rhGDF-5-coated and control implants. There was a small increase in induced bone height for implants coated with rhGDF-5 compared with the control, induced bone height averaging (+/-SD) 1.6+/-0.6 mm for implants coated with 120 microg rhGDF-5 versus 1.2+/-0.5, 1.2+/-0.6, and 0.6+/-0.2 mm for implants coated with 60 microg rhGDF-5, 30 microg rhGDF-5, or left uncoated, respectively (p<0.05). Bone formation was predominant at the lingual aspect of the implants. Narrow yellow and orange fluorescent markers throughout the newly formed bone indicate relatively slow new bone formation within 3-4 weeks. Implants coated with rhGDF-5 displayed limited peri-implant bone remodelling in the resident bone; the 120 microg dose exhibiting more advanced remodelling than the 60 and 30 microg doses. All treatment groups exhibited clinically relevant osseointegration. rhGDF-5-coated oral implants display a dose-dependent osteoinductive and/or osteoconductive effect, bone formation apparently benefiting from local factors. Application of rhGDF-5 appears to be safe as it is associated with limited, if any, adverse effects.

• Effect of nifedipine on gingival enlargement and periodontal breakdown in ligature-induced periodontitis in rats.

  Authors: Marilene Issa Fernandes, Eduardo José Gaio, Cristiano Susin, Cassiano Kuchenbecker Rösing, Rui Vicente Oppermann, Pantelis Varvaki Rados

  Archives of oral biology. 07/2010; 55(7):523-9.

  A recent consensus report could not find specific reports of the effect of nifedipine on the destruction of the periodontal tissues. The aim of the present study was to evaluate the effect ofA recent consensus report could not find specific reports of the effect of nifedipine on the destruction of the periodontal tissues. The aim of the present study was to evaluate the effect of nifedipine on gingival enlargement and periodontal breakdown using a ligature-induced periodontitis in rats. Fifty, male, 60 days old, Wistar rats, were divided into six groups. Cotton sutures were placed around the upper second molars. Two groups of 10 rats each did not receive ligatures and were treated daily with either saline solution or nifedipine 50mg/kg/day. Two groups of 10 rats received ligatures and were also treated daily with saline solution or nifedipine 50mg/kg/day. Two additional groups (nifedipine 10 and 100mg/kg/day) were included to explore a possible dose-response relationship. Animals were euthanatised at 30 days. Internal and oral epithelium, total and inflamed connective tissue, gingival thickness and height, and bone loss were assessed histologically. Nifedipine alone was not sufficient to promote gingival enlargement or periodontal destruction in the absence of the ligature. Compared to animals with ligatures only, the group that received ligatures and nifedipine 50mg/kg/day showed significant higher estimates for total and inflamed connective tissue, gingival thickness and height. No significant differences were observed for bone loss between these experimental groups. The other dosages of nifedipine did not provide additional information. Nifedipine itself did not lead to gingival enlargement in rats. In the presence of biofilm accumulation, nifedipine yielded greater gingival enlargement and periodontal inflammation, but it did not increase periodontal destruction.

• Periodontal wound healing/regeneration following the application of rhGDF-5 in a beta-TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogs.

  Authors: David H Kwon, Frederick C Bisch, Robert W Herold, Cornelius Pompe, Patrizia Bastone, Nancy A Rodriguez, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 07/2010; 37(7):667-74.

  The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal woundThe objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration. Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto beta-tricalcium phosphate (beta-TCP) particles and immersed in a bioresorbable poly(lactic-co-glycolic acid) (PLGA) composite or the beta-TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3-4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis. Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual beta-TCP particles were observed at 8 weeks for both rhGDF-5/beta-TCP/PLGA and beta-TCP/PLGA control sites. The rhGDF-5/beta-TCP/PLGA sites showed significantly greater cementum (2.34 +/- 0.44 versus 1.13 +/- 0.25 mm, p=0.02) and bone (2.92 +/- 0.66 versus 1.21 +/- 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/beta-TCP/PLGA sites but not in control sites. Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation.

• Periodontal healing following reconstructive surgery: effect of guided tissue regeneration using a bioresorbable barrier device when combined with autogenous bone grafting. A randomized-controlled trial 10-year follow-up.

  Authors: Per Nygaard-Østby, Vibeke Bakke, Oddny Nesdal, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 04/2010; 37(4):366-73.

  The objective of this 10-year randomized-controlled trial follow-up was to evaluate the stability of treatment outcomes following the implantation of autogenous bone graft with or without guidedThe objective of this 10-year randomized-controlled trial follow-up was to evaluate the stability of treatment outcomes following the implantation of autogenous bone graft with or without guided tissue regeneration (GTR) in the treatment of deep intra-bony periodontal defects. Forty patients exhibiting deep intra-bony periodontal defects were included in a randomized-controlled trial evaluating the adjunctive effect of GTR to autogenous bone graft. Twenty-six of 39 patients completing the original study were available for follow-up 10 years post-treatment. The patients had been included in a structured maintenance programme and were evaluated using the criteria of the original study by the same investigators. Significant improvements in the probing depth and clinical attachment level were observed for both groups between baseline and 9 months. Whereas the autogenous bone graft+GTR group showed significant improvements in probing bone levels and increased gingival recession at 9 months, no significant differences were observed for the autogenous bone graft group. Nine-month within-group results were maintained throughout the 10-year follow-up. Nevertheless, between-group comparisons at 10 years showed that the autogenous bone graft+GTR group exhibited significantly greater probing depth reduction (mean +/- SE: 4.2 +/- 0.5 versus 2.7 +/- 0.5 mm, p=0.023) and probing bone-level gain (3.9 +/- 0.8 versus 1.3 +/- 0.9 mm, p=0.034) than the autogenous bone graft group. Borderline significant differences between the autogenous bone graft+GTR and the autogenous bone graft groups were observed for clinical attachment level gain at 10 years (3.8 +/- 0.5 versus 2.2 +/- 0.7 mm, p=0.067), whereas no significant differences were observed for gingival recession (0.7 +/- 0.3 versus 0.6 +/- 0.5 mm, p>0.05). The results of this randomized study suggest that statistically significant differences were found with the adjunct use of GTR to an autogenous bone graft at 10 years. Nevertheless, these results should be interpreted with caution in light of its clinical relevance and biological rationale. Importantly, resolution of deep intra-bony periodontal defects can be maintained in the presence of a structured maintenance programme emphasizing high oral hygiene standards.

• Evaluation of an injectable rhGDF-5/PLGA construct for minimally invasive periodontal regenerative procedures: a histological study in the dog.

  Authors: David H Kwon, William Bennett, Samuel Herberg, Patrizia Bastone, Susanne Pippig, Nancy A Rodriguez, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 04/2010; 37(4):390-7.

  To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor-5 (rhGDF-5)/poly(lactic-co-glycolic acid) (PLGA) construct. Periodontal pockets (3 x 6 mm, width x depth) were surgically created over the buccal roots of the second and fourth mandibular pre-molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF-5/PLGA construct into the pockets were sequenced that four animals provided 2-/4-week and four animals 6-/8-week observations of sites receiving rhGDF-5/PLGA or serving as sham-surgery control. The rhGDF-5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 microg rhGDF-5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non-specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF-5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF-5/PLGA (p<0.01). In conclusion, the rhGDF-5/PLGA construct appears to be a safe technology for injectable, ease-of-use application of rhGDF-5-stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF-5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.

• Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs.

  Authors: Jaebum Lee, John F Decker, Giuseppe Polimeni, Carlo Alberto Cortella, Michael D Rohrer, John M Wozney, Jan Hall, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 03/2010; 37(6):582-90.

  Implants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partiallyImplants coated with recombinant human bone morphogenetic protein-2 (rhBMP-2) induce relevant bone formation but also resident bone remodelling. To compare the effect of implants fully or partially coated with rhBMP-2 on new bone formation and resident bone remodelling. Materials and Twelve, male, adult, Hound Labrador mongrel dogs were used. Critical-size, supraalveolar, peri-implant defects received titanium porous oxide surface implants coated in their most coronal aspect with rhBMP-2 (coronal-load/six animals) or by immersion of the entire implant in an rhBMP-2 solution (soak-load/six animals) for a total of 30 mug rhBMP-2/implant. All implants were air-dried. The animals were euthanized at 8 weeks for histometric evaluation. Clinical healing was uneventful. Supraalveolar bone formation was not significantly affected by the rhBMP-2 application protocol. New bone height and area averaged (+/- SE) 3.4 +/- 0.2 versus 3.5 +/- 0.4 mm and 2.6 +/- 0.4 versus 2.5 +/- 0.7 mm(2) for coronal-load and soak-load implants, respectively (p>0.05). The corresponding bone density and bone-implant contact (BIC) recordings averaged 38.0 +/- 3.8%versus 34.4 +/- 5.6% and 25.0 +/- 3.8%versus 31.2 +/- 3.3% (p>0.05). In contrast, resident bone remodelling was significantly influenced by the rhBMP-2 application protocol. Bone density outside the implants threads averaged 74.7 +/- 3.8% and 50.8 +/- 4.1% for coronal-load and soak-load implants, respectively (p<0.05); bone density within the thread area averaged 51.8 +/- 1.2% and 37.8 +/- 2.9%, and BIC 70.1 +/- 6.7% and 43.3 +/- 3.9% (p<0.05). Local application of rhBMP-2 appears to be a viable technology to support local bone formation and osseointegration. Coronal-load implants obviate resident bone remodelling without compromising new bone formation.

• Alveolar ridge augmentation using implants coated with recombinant human bone morphogenetic protein-7 (rhBMP-7/rhOP-1): histological observations.

  Authors: Cristiano Susin, Mohammed Qahash, Giuseppe Polimeni, Ping Hung Lu, Hari S Prasad, Michael D Rohrer, Jan Hall, Ulf M E Wikesjö

  Journal of clinical periodontology. 03/2010; 37(6):574-81.

  Pre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bonePre-clinical studies have shown that recombinant human bone morphogenetic protein-2 (rhBMP-2) coated onto purpose-designed titanium porous-oxide surface implants induces clinically relevant bone formation and osseointegration. The objective of this study was to examine the potential of rhBMP-7, also known as recombinant human osteogenic protein-1 (rhOP-1), coated onto titanium porous-oxide surface implants to support vertical alveolar ridge augmentation and implant osseointegration. Bilateral, critical-size, 5 mm, supraalveolar peri-implant defects were created in six young adult Hound Labrador mongrel dogs. The animals received implants coated with rhBMP-7 at 1.5 or 3.0 mg/ml randomized to contra-lateral jaw quadrants. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants for primary intention healing. The animals received fluorescent bone markers at 3, 4, 7, and 8 weeks post-surgery when they were euthanized for histological evaluation. Without striking differences between treatments, the implant sites exhibited a swelling that gradually regressed to become hard to palpation disguising the implant contours. The histological evaluation showed robust bone formation; the newly formed bone assuming characteristics of the contiguous resident bone, bone formation (height and area) averaging 4.1+/-1.0 versus 3.6+/-1.7 mm and 3.6+/-1.9 versus 3.1+/-1.8 mm(2); and bone density 56%versus 50% for implants coated with rhBMP-7 at 1.5 and 3.0 mg/ml, respectively. Both treatments exhibited clinically relevant osseointegration, the corresponding bone-implant contact values averaging 51% and 47%. Notable peri-implant resident bone remodelling was observed for implants coated with rhBMP-7 at 3.0 mg/ml. rhBMP-7 coated onto titanium porous-oxide surface implants induces clinically relevant local bone formation including osseointegration and vertical augmentation of the alveolar ridge, the higher concentration/dose associated with some local side effects.

• Periodontal regeneration: focus on growth and differentiation factors.

  Authors: Jaebum Lee, Andreas Stavropoulos, Cristiano Susin, Ulf M E Wikesjö

  Dental clinics of North America. 01/2010; 54(1):93-111.

  Several growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitableSeveral growth and differentiation factors have shown potential as therapeutic agents to support periodontal wound healing/regeneration, although optimal dosage, release kinetics, and suitable delivery systems are still unknown. Experimental variables, including delivery systems, dose, and the common use of poorly characterized preclinical models, make it difficult to discern the genuine efficacy of each of these factors. Only a few growth and differentiation factors have reached clinical evaluation. It appears that well-defined discriminating preclinical models followed by well-designed clinical trials are needed to further investigate the true potential of these and other candidate factors. Thus, current research is focused on finding relevant growth and differentiation factors, optimal dosages, and the best approaches for delivery to develop clinically meaningful therapies in patient-centered settings.

• The critical-size supraalveolar peri-implant defect model: reproducibility in histometric data acquisition of alveolar bone formation and osseointegration.

  Authors: Jaebum Lee, Quoc Tran, Gary Seeba, Ulf M E Wikesjö, Cristiano Susin

  Journal of clinical periodontology. 12/2009; 36(12):1067-74.

  OBJECTIVE: The objective of this report is to present the reproducibility of outcomes assessments in the Critical-Size Supraalveolar Peri-Implant Defect Model. MATERIALS AND METHODS: Two examinersOBJECTIVE: The objective of this report is to present the reproducibility of outcomes assessments in the Critical-Size Supraalveolar Peri-Implant Defect Model. MATERIALS AND METHODS: Two examiners without specific experience in histological analysis and one experienced examiner performed the histometric evaluation. A comprehensive training program in data acquisition and histological analysis was established, the inexperienced examiners underwent approximately 12 h of training over multiple sessions. A custom-designed image analysis software macro and a computer-based image system were used to analyse digital images generated by a microscope camera system. Nine parameters for newly formed and resident bone were evaluated. Examiners performed histometric analysis using 36 histologic sections selected from critical-size supraalveolar peri-implant defects in 12 male Hound Labrador Mongrel dogs. Buccal and lingual measurements were performed in 72 sites. Intra- and inter-examiner reproducibility were evaluated using the concordance correlation coefficient (CCC) and means +/- SD of the differences. Systematic errors were evaluated using an F-test for equality of means and variances. RESULTS: Intra-examiner reproducibility was high for all parameters evaluated, the lowest CCC observed being 0.87. Inter-examiner reproducibility was also high, most CCCs exceeding 0.90. Minor systematic errors for intra- and inter-examiner comparisons were occasionally observed. The results imply a high temporal stability because recordings were performed 3 months apart. Measurement errors were stable throughout the range of observations for all parameters. CONCLUSIONS: High examiner reproducibility and temporal stability can be achieved for histometric data acquisition using the Critical-Size Supraalveolar Peri-Implant Defect Model. Examiner reproducibility should be routinely assessed, reported, and accounted for to assure the quality of evidence generated by preclinical studies.

• Association among menopause, hormone replacement therapy, and periodontal attachment loss in southern brazilian women.

  Authors: Alex N Haas, Cassiano K Rösing, Rui V Oppermann, Jasim M Albandar, Cristiano Susin

  Journal of periodontology. 09/2009; 80(9):1380-7.

  Background: The aim of the present study was to evaluate the association among menopause, hormone replacement therapy (HRT), and periodontal attachment loss (PAL). Methods: Three hundred twenty-eightBackground: The aim of the present study was to evaluate the association among menopause, hormone replacement therapy (HRT), and periodontal attachment loss (PAL). Methods: Three hundred twenty-eight women (40 to 69 years old) who participated in a previous oral survey in South Brazil were included. Women who reported not having their monthly menstrual cycles for >/=12 months were classified as postmenopausal. Postmenopausal women were categorized according to HRT. Women with >/=30% teeth with PAL >/=5 mm were classified as having periodontitis. The data were analyzed using a multivariable logistic regression model and adjusted for age, smoking, socioeconomic status, and dental care. Results: The prevalence of periodontitis was significantly greater among postmenopausal women not using HRT (HRT-) than among premenopausal women (64.4% versus 46.3%; P = 0.005). Similarly, the multivariable analysis demonstrated a significantly higher chance of having periodontitis in postmenopausal HRT- women than in premenopausal women (odds ratio [OR], 2.1; 95% confidence interval [CI]: 1.1 to 4.0). In contrast, no significant differences were observed in the prevalence of periodontitis between postmenopausal women using HRT (HRT+) and premenopausal women (48.8% versus 46.3%; P = 0.77). After adjusting for cofactors, postmenopausal HRT+ women did not have a greater likelihood of having periodontitis than premenopausal women (OR, 1.2; 95% CI: 0.6 to 2.5). No significant differences in tooth loss were observed among the study groups after adjusting for confounders. Conclusions: Postmenopausal HRT- women had a greater chance of having periodontitis than premenopausal women. In contrast, postmenopausal HRT+ women and premenopausal women had similar periodontal status. HRT may have a beneficial effect on periodontal health.

• Evaluation of nano-technology-modified zirconia oral implants: a study in rabbits.

  Authors: Jaebum Lee, Janet H Sieweke, Nancy A Rodriguez, Peter Schüpbach, Håkan Lindström, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 07/2009; 36(7):610-7.

  OBJECTIVE: The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration. MATERIALSOBJECTIVE: The objective of this study was to screen candidate nano-technology-modified, micro-structured zirconia implant surfaces relative to local bone formation and osseointegration. MATERIALS AND METHODS: Proprietary nano-technology surface-modified (calcium phosphate: CaP) micro-structured zirconia implants (A and C), control micro-structured zirconia implants (ZiUnite), and titanium porous oxide implants (TiUnite) were implanted into the femoral condyle in 40 adult male New Zealand White rabbits. Each animal received one implant in each hind leg; thus, 20 animals received A and C implants and 20 animals received ZiUnite and TiUnite implants in contralateral hind legs. Ten animals/group were euthanized at weeks 3 and 6 when biopsies of the implant sites were processed for histometric analysis using digital photomicrographs produced using backscatter scanning electron microscopy. RESULTS: The TiUnite surface demonstrated significantly greater bone-implant contact (BIC) (77.6+/-2.6%) compared with the A (64.6+/-3.6%) and C (62.2+/-3.1%) surfaces at 3 weeks (p<0.05). Numerical differences between ZiUnite (70.5+/-3.1%) and A and C surfaces did not reach statistical significance (p>0.05). Similarly, there were non-significant differences between the TiUnite and the ZiUnite surfaces (p>0.05). At 6 weeks, there were no significant differences in BIC between the TiUnite (67.1+/-4.2%), ZiUnite (69.7+/-5.7%), A (68.6+/-1.9%), and C (64.5+/-4.1%) surfaces (p>0.05). CONCLUSION: TiUnite and ZiUnite implant surfaces exhibit high levels of osseointegration that, in this model, confirm their advanced osteoconductive properties. Addition of CaP nano-technology to the ZiUnite surface does not enhance the already advanced osteoconductivity displayed by the TiUnite and ZiUnite implant surfaces.

• Regenerative potential and healing dynamics of the periodontium: a critical-size supra-alveolar periodontal defect study.

  Authors: Giuseppe Polimeni, Cristiano Susin, Ulf M E Wikesjö

  Journal of clinical periodontology. 04/2009; 36(3):258-64.

  OBJECTIVES: The nature and characteristics of the newly formed periodontium obtained following regenerative procedures remain a matter of controversy. The objective of this study was to evaluate theOBJECTIVES: The nature and characteristics of the newly formed periodontium obtained following regenerative procedures remain a matter of controversy. The objective of this study was to evaluate the regenerative potential of the periodontal attachment and healing dynamics as observed from the spatial distribution of newly formed cementum, periodontal ligament (PDL) and alveolar bone following optimal circumstances for wound healing/regeneration in a discriminating animal model. MATERIAL AND METHODS: Critical-size, 6-mm, supra-alveolar, periodontal defects were surgically created in six young adult Beagle dogs. Space-providing ePTFE devices with 300-microm laser-drilled pores were implanted to support wound stability and space provision in one jaw quadrant/animal. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced to submerge the defect sites for primary intention healing. Histometric analysis followed an 8-week healing interval. RESULTS: Healing was uneventful in all animals. The histometric analysis showed that cementum regeneration (2.99 +/- 0.22 mm) was significantly greater than PDL (2.54 +/- 0.18 mm, p=0.03) and bone regeneration (2.46 +/- 0.26 mm, p=0.03). The wound area showed significant positive non-linear effect on cementum (log beta=1.25, p<0.001), PDL (log beta=1.24, p<0.001) and new bone formation (log beta=1.36, p<0.001). A high degree of concordance and significant linear relationship was observed between cementum, PDL and bone regeneration indicating that their formation virtually occurred in parallel. CONCLUSIONS: Cementum, PDL and alveolar bone virtually regenerate in parallel under optimal circumstances for periodontal wound healing/regeneration. Moreover, space provision positively influences the extent of periodontal regeneration.