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OBJECTIVE: Novel implant technologies and reconstructive therapies for alveolar augmentation require pre-clinical evaluation to estimate their biologic potential, efficacy, and safety before clinical application. The objective of this report is to present characteristics and use of the critical-size, supraalveolar, peri-implant defect model. METHODS: Bilateral extraction of the mandibular premolars was performed in 12 Hound Labrador mongrel dogs following horizontal surgical cut-down of the alveolar ridge approximating 6 mm. Each jaw quadrant received three custom-produced TiUnite, phi 4.0 x 10 mm threaded implants placed into osteotomies prepared into the extraction sites of the third and fourth premolars. The implants exhibited a reference notch 5 mm from the implant platform to facilitate surgical placement leaving 5 mm of the implant in a supraalveolar position, and to serve as a reference point in the radiographic, histologic and histometric analysis. The implants were submerged under the mucoperiosteal flaps for primary intention healing. Fluorescent bone markers were administered at weeks 3 and 4 post-surgery, and pre-euthanasia. The animals were euthanized following an 8-week healing interval when block biopsies were collected for analysis. RESULTS: Healing was generally uneventful. The radiographic and histometric evaluations demonstrate the limited osteogenic potential of this defect model. Whereas lingual peri-implant sites exhibited a mean (+/-SE) bone gain of 0.4+/-0.1 mm, resorption of the buccal crestal plate resulted in a mean bone loss of 0.4+/-0.2 mm for an overall osteogenic potential following sham-surgery averaging 0.0+/-0.1 mm. Overall bone density and bone-implant contact in the contiguous resident bone averaged 79.1+/-1.1% and 76.9+/-2.3%, respectively. CONCLUSION: The results suggest that the critical-size, supraalveolar, peri-implant defect model appears a rigorous tool in the evaluation of candidate technologies for alveolar reconstruction and osseointegration of endosseous oral implants. Limited innate osteogenic potential allows critical evaluation of osteogenic, osteoconductive, or osteoinductive technologies in a challenging clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate, (i) if subjects submitted to a structured oral hygiene training program (OHt) maintain adopted habits over 180 days without professional guidance; and (ii) in perspective whether flossing provides additional benefits to toothbrushing on gingival health., Materials and Methods: Seventy-five adult subjects showing approximately 40% proximal gingival bleeding were randomized to receive OHt (1 session weekly over 8 weeks) using toothbrush and dental floss or toothbrush alone. The subjects were then followed over 180 days without professional guidance. Primary outcomes were mean interproximal Gingival Index (GI) and GI = 2 (gingival bleeding). Mixed linear models were used for the comparison between groups (p < 0.05)., Results: 68 subjects received OHt, 48 subjects completed the 180-day follow-up. Subjects maintained adequate oral hygiene routines. Besides a reduction in gingival inflammation, no alterations in gingival status were observed among groups, subjects additionally instructed to use dental floss showing a mean interproximal GI = 2 of 12.8 ± 2.5 compared with 19.8 ± 2.2 for subjects limited to tooth brushing alone., Conclusions: OHt intensive training promotes gingival health and maintenance lasting at least 6 months without professional supervision reinforcing important principles: (i) dental health professionals should dedicate time training and motivating their patients to reach adequate self-performed plaque control; and (ii) the adjunctive use of dental floss appears essential to reduce interproximal gingival inflammation in subjects with intact interdental papillae., Clinical Relevance: Dentists need to invest time in training/motivating/engage their patients to achieve adequate OH; adjunct flossing in subjects with papilla filling the interdental space appears essential to reach and maintain gingival health., Clinicaltrials: GOV : (53831716.5.0000.5346)., Trial Registration: The protocol registration was filed May 9, 2018 (# 538,311,716.5.0000.5346) on ClinicalTrials.gov. An NCT number (NCT04909840) was generated upon completed registration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Natural (bovine-/equine-/porcine-derived) or synthetic hydroxyapatite (HA) biomaterials appear to be the preferred technologies among clinicians for bone augmentation procedures in preparation for implant dentistry. The aim of this study was to screen candidate HA biomaterials intended for alveolar ridge augmentation relative to their potential to support local bone formation/maturation and to assess biomaterial resorption using a routine critical-size rat calvaria defect model., Methods: Eighty adult male Sprague Dawley outbred rats obtained from a approved-breeder, randomized into groups of ten, were used. The calvaria defects (ø8 mm) either received sham surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA (Cerabone, DirectOss, 403Z013), and bovine (403Z014) or synthetic HA/ß-TCP (Reprobone, Ceraball) constructs. An 8 wk healing interval was used to capture the biomaterials' resolution., Results: All biomaterials displayed biocompatibility. Strict HA biomaterials showed limited, if any, signs of biodegradation/resorption, with the biomaterial area fraction ranging from 22% to 42%. Synthetic HA/ß-TCP constructs showed limited evidence of biodegradation/erosion (biomaterial area fraction ≈30%). Mean linear defect closure in the sham-surgery control approximated 40%. Mean linear defect closure for the Bio-Oss reference control approximated 18% compared with 15-35% for the candidate biomaterials without significant differences between the controls and candidate biomaterials., Conclusions: None of the candidate HA biomaterials supported local bone formation/maturation beyond the native regenerative potential of this rodent model, pointing to their limitations for regenerative procedures. Biocompatibility and biomaterial dimensional stability could suggest their potential utility as long-term defect fillers.

Objectives: The objective of this report was to provide a review of the minipig intraoral dental implant model including a meta-analysis to estimate osseointegration and crestal bone remodeling., Methods: A systematic review including PubMed and EMBASE databases through June 2021 was conducted. Two independent examiners screened titles/abstracts and selected full-text articles. Studies evaluating titanium dental implant osseointegration in native alveolar bone were included. A quality assessment of reporting was performed. Random-effects meta-analyses and meta-regressions were produced for bone-implant contact (BIC), first BIC, and crestal bone level., Results: 125 out of 249 full-text articles were reviewed, 55 original studies were included. Quality of reporting was generally low, omissions included animal characteristics, examiner masking/calibration, and sample size calculation. The typical minipig model protocol included surgical extraction of the mandibular premolars and first molar, 12±4 wks post-extraction healing, placement of three narrow regular length dental implants per jaw quadrant, submerged implant healing and 8 wks of osseointegration. Approximately 90% of studies reported undecalcified incandescent light microscopy histometrics. Overall, mean BIC was 59.88% (95%CI: 57.43-62.33). BIC increased significantly over time (p<0.001): 40.93 (95%CI: 34.95-46.90) at 2 wks, 58.37% (95%CI: 54.38-62.36) at 4 wks, and 66.33% (95%CI: 63.45-69.21) beyond 4 wks. Variability among studies was mainly explained by differences in observation interval post-extraction and post-implant placement, and implant surface. Heterogeneity was high for all studies (I2 > 90%, p<0.001)., Conclusions: The minipig intraoral dental implant model appears to effectively demonstrate osseointegration and alveolar bone remodeling similar to that observed in humans and canine models., Competing Interests: CS serves as scientific advisor and lecturer for Nobel Biocare AG. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Periodontal disease is a major cause of tooth loss. Few studies have evaluated the residual area of the periodontal ligament in extracted teeth and, to the best of our knowledge, none from Latin America have done so regarding indications for extraction. The aim of this study was to evaluate the residual periodontal ligament (RPL) with respect to indication for extraction in a sample of teeth from a Brazilian Public Health Service district., Materials and Methods: All teeth extracted within the Public Health Service district of Santa Maria, Brazil, over a 5-month period were requested for analysis. A total of 414 teeth eligible for measurement were stained and evaluated for RPL using a stereo microscope. Participating Public Health Service dentists completed a questionnaire detailing demographic variables and indication for each extracted tooth. The percentage of RPL was determined for each tooth. Comparisons of RPL between teeth extracted on periodontal versus other indications were made using the Mann-Whitney test., Results: RPL averaged 34.8% for teeth extracted on periodontal indications versus 79.5% for other teeth (P ≤ 0.001). When considering teeth with an RPL ≥ 30% as possible to maintain, 189 (76%) of the teeth extracted on periodontal indications could have been maintained. When RPL cut-off limits of ≥ 40% or ≥ 50% are applied, 93 (37%) and 43 (17%) teeth, respectively, could have been maintained., Conclusion: This study suggests that strictly based on RPL, a large number of teeth extracted on periodontal indications conceivably could be maintained., (© 2020 FDI World Dental Federation.)

Aim: This randomized clinical trial evaluated the effect of the frequency of self-performed mechanical plaque control (SPC) on gingival health in subjects with a history of periodontitis., Materials and Methods: Forty-two subjects participating in a routine periodontal maintenance program were randomized to perform SPC at 12-, 24- or 48-hr intervals. Plaque index (PlI) and gingival index (GI) were evaluated at baseline, and days 15, 30 and 90 of study. Probing depths, clinical attachment levels and bleeding on probing were assessed at baseline, days 30 and 90. Mixed linear models were used for the analysis and comparison of experimental groups., Results: Mean GI at baseline remained unchanged throughout study (90 days) only in the 12-hr group (0.7 ± 0.1 versus 0.8 ± 0.1; p < .05). At the end of study, mean GI was significantly increased in the 48-hr group over that in the 12- and 24-hr groups. When GI = 2 scores were considered, only the 48-hr group failed to maintain gingival health throughout the study (18.8%)., Conclusion: SPC performed at a 12- or 24-hr frequency appears sufficient to controlling gingival inflammation whereas this clinical status was not maintained using a 48-hr frequency in subjects with a history of periodontitis subject to a routine periodontal maintenance program (ClinicalTrials.gov: 50208115.9.0000.5346)., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) has been shown to support significant bone formation when used to augment the maxillary sinus for implant dentistry. Nevertheless, bone biomaterials have been suggested to extend rhBMP-2/ACS with limited support of the merits of such approaches., Objectives: To evaluate local bone formation/dental implant osseointegration following implantation of rhBMP-2/ACS combined with a ceramic bone biomaterial using a mini-pig sinus augmentation model., Methods: Twelve adult Göttingen mini-pigs received rhBMP-2/ACS (rhBMP-2 adjusted to 0.43 mg/cc) alone or combined with an off-the-shelf biphasic ceramic (15%/85% HA/ß-TCP) biomaterial at 3:1, 1:1 and 1:3 ratios randomized to contra-lateral maxillary sinus sites yielding rhBMP-2/ACS fractions of 100%, 75%, 50% and 25%, respectively. A 4-cc implant volume was used for all sites. Two threaded dental implants (ø4.0 × 11.5 mm) were placed at each site. The animals were euthanized at 8 weeks for histologic analysis., Results: Surgical execution and healing were generally uneventful, infraorbital local swelling was observed in all animals until suture removal. rhBMP-2/ACS combined with the ceramic biomaterial did not significantly enhance local bone formation (range 9.0 ± 1.5 to 9.7 ± 2.1 mm) compared with rhBMP-2/ACS alone (8.6 ± 1.1 mm; p > 0.05). Variations in rhBMP-2/ACS to ceramic matrix ratios yielding rhBMP-2 doses approximating 0.4, 0.9, 1.3 and 1.7 mg/sinus did not appreciably influence bone formation/osseointegration., Conclusions: Whereas rhBMP-2/ACS supports significant bone formation/osseointegration in the mini-pig sinus augmentation model and thus appears an effective alternative for sinus augmentation procedures, adding a ceramic biomaterial to rhBMP-2/ACS does not produce meaningful biological advantages., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To screen candidate biomaterials intended for alveolar augmentation relative to their potential to enhance local bone formation using a routine critical-size (ø8-mm) rat calvaria defect model., Methods: One hundred and forty male Sprague Dawley outbred rats, age 11-12 weeks, weight 325-375 g, obtained from USDA approved breeder, randomised into 14 groups of 10 animals, each received one of the following treatments: sham-surgery (empty control), Bio-Oss (bovine HA/reference control), or candidate biomaterials including bovine HA, synthetic HA/ß-TCP and calcium phosphate constructs, mineralised/demineralised human bone preparations, a ß-TCP/calcium sulphate and an HA/calcium sulphate putty. A 4-week healing interval was chosen to discern local bone formation using incandescent and polarised light microscopy. Statistical analysis used one-way ANOVA followed by Bonferroni for pairwise comparisons., Results: Candidate biomaterials all displayed biocompatibility. They exhibited limited, if any, appreciable bioerosion or biodegradation. No statistically significant differences in mean linear defect closure were observed among experimental groups, sham-surgery displaying the highest score (48.1 ± 24.3%). Sham-surgery also showed a significantly greater bone area fraction than all other groups (19.8 ± 13.9%, p < .001). The HA/calcium sulphate putty showed a significantly greater residual biomaterial area fraction than all other groups (61.1 ± 8.5%, p < .01)., Conclusion: Within the limitations of this animal model, although biocompatible, none of the tested biomaterials enhanced local bone formation beyond the innate regenerative potential of this craniotomy defect., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Avoiding excessive trauma--thermal or otherwise--during dental implant site preparation is considered critical to implant success; overheating is considered to be a major cause of bone necrosis. Studies evaluating thermal and mechanical effects of implant drill design are limited, and effects of flute design have not been accounted for. The purpose of this study was to compare heat generation and cutting efficiency associated with two-, three-, and four-fluted implant drills to investigate the optimal number of flutes., Materials and Methods: Two-, three-, and four-fluted dental implant drills with identical point, relief, and rake angles and otherwise standard dimensions were evaluated. Real-time temperature changes while drilling artificial bone were recorded using an infrared thermal imager. Cutting efficiency was assessed as the drilling time to a 15-mm depth under constant load using a specially designed recording system. Each drill variation was examined 20 times. A one-way analysis of variance was used for statistical analysis., Results: Mean temperature increases amounted to 8.3°C, 10.8°C, and 15.1°C for two-, three-, and four-fluted drills, respectively; temperatures significantly increased (P < .001) with an increased number of flutes. Mean drilling time serving as a measure of cutting efficiency amounted to 2.6, 2.5, and 2.5 seconds for the two-, three-, and four-fluted drills, respectively. A trend of cutting efficiency increasing or decreasing according to the number of flutes was not observed. Differences in cutting efficiency among the three drill variations were statistically significant (P = .015). The cutting efficiency of the three-fluted drill was superior to that of the two-fluted drill (P = .016)., Conclusion: Within the limitations of the study, a two-fluted drill would be preferred for osteotomy preparation due to its level of heat generation, whereas a three-fluted drill showed favorable cutting efficiency.

Aim: The objective of this report was to present histological characteristics and gene expression profile of newly formed bone following horizontal augmentation of the atrophic anterior maxilla using recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier (rhBMP-2/ACS) versus an autogenous bone graft (ABG)., Methods: Bone core biopsies from 24 subjects participating in a randomized clinical trial were obtained at dental implant placement, 6 months following alveolar ridge augmentation using rhBMP-2/ACS (rhBMP-2 at 1.5 mg/ml; total dose 4.2 mg) or a particulate ABG harvested from the mandibular retro-molar region. A titanium mesh was used to provide wound stability and space for bone formation. Analysis included histological/histometric observations and gene expression profile of the newly formed bone., Results: rhBMP-2/ACS yielded bone marrow rich in capillaries, undifferentiated cells and bone lining cells compared with the ABG (p = 0.002). Whereas no significant differences were observed in total bone fraction (p = 0.53), non-vital bone particles trapped in lamellar vital bone were observed in the ABG group (p < 0.001). Real-time PCR showed greater BMP-2 and RUNX2 expression for rhBMP-2/ACS over the ABG (p = 0.001 and 0.0021, respectively), while the ABG exhibited greater expression of RANKL:OPG, BSP and OPN over rhBMP-2/ACS (p = 0.01, 0.005 and 0.0009, respectively)., Conclusions: Our observations suggest that formative biological processes explain bone formation following implantation of rhBMP-2/ACS, whereas remodelling, resorptive/formative processes, characterizes sites receiving ABGs., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Various advanced technologies have been designed to estimate dental implant stability, including insertion torque, implant damping using the Periotest, and resonance frequency analysis expressed in implant stability quotient units. This study aimed to establish the relationship between the estimates for these three techniques., Materials and Methods: Bovine cortical bone blocks were trimmed to square shapes of precisely controlled thickness and density. Thereafter, 4-mm-diameter × 10-mm-long implants were placed in the bone blocks using 30-, 45-, and 60-Ncm insertion torques. Implant damping and resonance frequency analysis were conducted at four angles for each implant. Spearman correlation coefficients were calculated to examine the relationship between insertion torque, resonance frequency analysis, and implant damping measured values., Results: Resonance frequency analysis and implant damping estimates exhibited a strong inverse correlation (r = -0.98, P < .001). A linear equation was formulated: Periotest value = 15.54 + (-0.26 × implant stability quotient). Implant damping and resonance frequency estimates revealed a weak correlation with insertion torque (P < .05)., Conclusion: This study mathematically defined a linear correlation between implant damping and resonance frequency estimates, thereby providing a guide for clinicians when deciding the loading time for dental implants using the implant damping or resonance frequency estimates.

Background: Physiologic remodeling resulting in crestal bone loss appears a common corollary to dental implant surgery. Several hypotheses and clinical strategies have been advanced to explain and avert crestal remodeling; however, causative mechanisms remain unclear and the efficacy of clinical protocols uncertain., Purpose: The objective of the present study was to provide a histologic account of crestal bone levels and mucosal profile at implant sites receiving platform shift/switch and standard abutments following conventional flap surgery and subcrestal implant placement in presence or absence of crestal gap defects using a dog model., Materials and Methods: Four dental implants were placed into the left/right edentulated posterior mandible in five adult male Hound Labrador mongrel dogs using flap surgery including subcrestal placement with/without a 1 × 5 mm (width × depth) gap defect, and using platform shift/switch and standard abutments. Block biopsies were collected for histological/histometric analysis following an 8-week healing interval., Results: No significant differences in crestal resorption were observed among experimental groups; crestal resorption being significantly more advanced at buccal than at lingual sites (p < .001). Similarly, crestal bone-implant contact was not significantly different among groups; crestal bone-implant contact being consistently below the implant platform at buccal sites (p < .01). Moreover, the peri-implant mucosal profile was not statistically different among groups, the mucosal height being significantly greater at buccal than at lingual sites (p < .001). Also, no significant differences among groups were observed for the apical extension of the epithelial attachment, the epithelial attachment being arrested more than 2 mm above the implant platform at both platform shift/switch and standard abutments., Conclusions: Using a clinical strategy including flap surgery and subcrestal implant placement, implant technology comparing platform shift/switch with standard abutments, surgical approach, and abutment selection seems to have a limited impact on crestal remodeling, associated bone loss, and mucosal profile., (© 2014 Wiley Periodicals, Inc.)

Background: Crestal remodeling/bone loss appears a common sequel to dental implant placement. Several hypotheses and clinical strategies have been advanced to explain and avert crestal remodeling; however, causative mechanisms remain unclear and the efficacy of clinical protocol uncertain., Objective: The objective of the present study was to provide a histologic record of crestal versus subcrestal implant placement on crestal remodeling and mucosal profile comparing platform shift/switch and standard abutments following flapless implant surgery using a dog model., Methods: Four dental implants each were placed into the left and right edentulated posterior mandibles in five adult male hound-Labrador mongrel dogs using a flapless approach including crestal versus subcrestal placement and using platform shift versus standard abutments. Block biopsies were collected for histological/histometric analysis following an 8-week healing interval., Results: Both crestal and subcrestal implant installation resulted in significant crestal remodeling and bone loss, in particular at buccal sites, without significant differences between platform shift/switch and standard abutments. Implants installed subcrestally exhibited a significantly taller mucosal profile over crestal-level implants without significant differences between platform shift/switch and standard abutments; the epithelial attachment at all times arrested on the abutment surface., Conclusions: Comparing platform shift/switch versus standard abutments using a minimally invasive flapless approach including crestal or subcrestal implant placement, the platform shift/switch abutments offer no selective advantage over standard abutments., (© 2014 Wiley Periodicals, Inc.)

Purpose: The aim of this systematic review was to evaluate current and emerging regenerative approaches for implant site development in the edentulous atrophic maxilla using tissue engineering and regenerative medicine (TERM) principles and to identify priorities for future research., Materials and Methods: Two independent examiners conducted a comprehensive search using specific keywords to identify original clinical studies using TERM for implant site development in the edentulous atrophic maxilla including indications for alveolar ridge preservation, horizontal alveolar augmentation, maxillary sinus augmentation, and augmentation of severe vertical or combined defects. Endpoints included clinical, radiographic, histologic, and patient-centered outcomes., Results: The initial search identified 3,061 articles. The final selection included 89 articles, of which 12 evaluated alveolar ridge preservation, 6 horizontal defects, 61 maxillary sinus augmentation, and 11 management of severe vertical or combined defects. A summary of the main findings relative to the effect of TERM-based approaches applied for implant site development in the atrophic maxillary segments is presented. Marked heterogeneity among included studies prevented meaningful quantitative analysis. The following relevant effects of TERM-based therapies for site development in the edentulous atrophic maxilla were observed: (1) recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier increased bone augmentation; (2) recombinant human platelet-derived growth factor BB in combination with freeze-dried bone allograft or beta tricalcium phosphate accelerated bone formation through accelerated remodeling of carrier biomaterials; (3) autologous cell therapy enhanced clinical and radiographic outcomes; (4) autologous cell therapy in alveolar ridge preservation provided superior histomorphometric outcomes (vital bone formation) at 6 weeks; and (5) platelet-rich plasma formulations combined with autologous bone grafts for maxillary sinus augmentation increased radiographic density and accelerated bone mineralization at 6 months., Conclusion: Clinical success has been demonstrated with the application of different TERM modalities for implant site development in the edentulous atrophic maxilla. However, indications are narrow and further study is needed. Clinical trials assessing meaningful outcomes, involving larger populations, and with longer follow-up are warranted to discern the effectiveness of the achieved results compared with a valid control.

Background: Crestal remodeling/bone loss appears to be a common sequel to dental implant placement. Several hypotheses/clinical strategies have been proposed to explain/avert crestal remodeling; however, causative mechanisms remain unclear and the efficacy of these clinical approaches uncertain., Objective: The objective of the present study was to provide a histological account of crestal bone levels and mucosal profile at platform shift/switch and concave abutments following flapless and conventional flap surgery and subcrestal implant placement using a dog model., Methods: Four dental implants each were placed in the left/right mandibular posterior jaw quadrants in five adult male Hound/Labrador mongrel dogs using flap surgery with a 1 × 5 mm gap defect or using a flapless approach, both involving placement 2 mm subcrestally and platform shift/switch versus concave abutments. Block biopsies for histological/histometric analysis were collected at 8 weeks., Results: No significant differences were observed regarding crestal bone levels, with all groups showing mean bone levels above the implant platform. Similarly, crestal bone-implant contact was not significantly different among groups. Moreover, peri-implant mucosal profiles were not statistically different among groups for buccal sites; average mucosal height reached 4.1 to 4.9 mm above the implant platform. Comparison between buccal and lingual sites showed a nonsignificant tendency toward greater crestal resorption at buccal sites, adjusting for other factors. Mean crestal bone-implant contact level approximated the implant platform for lingual sites while consistently remaining below the platform at the buccal sites. Peri-implant mucosal height was significantly higher at buccal than at lingual sites, with the epithelial attachment located a significant distance away from the implant platform at buccal sites., Conclusions: The surgical approaches (subcrestal implant placement by flap surgery or a flapless approach) and abutment designs (platform shift/switch or concave) used in this study seem to have a limited impact on crestal remodeling, associated bone loss, and mucosal profile. Bioclinical strategies should be developed to circumvent the limitations of current clinical protocol., (© 2014 Wiley Periodicals, Inc.)

Objectives: The objective of this study was to evaluate bone formation/osseointegration following surgical treatment of experimental peri-implantitis at dental implants with different surface characteristics exposed to ligature-induced breakdown conditions., Methods: Ten turned (control), 10 sandblasted/acid-etched (SA), and 10 SA/hydroxyapatite nanocoated (HA) implants were installed into the edentulated posterior mandible in five Beagle dogs and allowed to osseointegrate for 12 weeks. Ligature-induced breakdown defects were then induced over 23 weeks using stainless steel wire ligatures. The ligatures were removed and soft tissues were allowed to heal for 3 weeks. Next, exposed implant surfaces were decontaminated followed by guided bone regeneration using a collagen membrane and submerged wound healing. The animals were euthanized for histometric analysis at 12 weeks post-surgery., Results: The radiographic analysis showed vertical bone loss following ligature-induced breakdown without statistically significant differences among implant technologies. The histometric analysis showed significantly enhanced bone formation (height) at SA and SA/HA compared with turned implants (p = 0.028) following reconstructive surgery. Bone formation area was greater at SA/HA compared with turned implants, however the difference did not reach statistical significance., Conclusions: While ligature-induced defect progression does not appear implant surface dependent in this animal model, bone formation at the decontaminated implant surfaces appears more favourable at SA and SA/HA over turned implants following reconstructive surgery., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Poly(L-lactide)-co-(epsilon-caprolactone) [poly(LLA-co-CL)] and poly(L-lactide)-co-(1,5-dioxepan-2-one) [poly(LLA-co-DXO)] are being considered candidate scaffolds for bone tissue engineering. We evaluated the bioactive potential of poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds loaded with low-dose bone morphogenetic protein-2 (BMP-2). Periodontal ligament (PDL) cells were cultured onto the various scaffolds loaded with 1 µg BMP-2 or without BMP-2 (control). Cell viability, attachment, and proliferation were determined using a methylthiazol tetrazolium (MTT) colorimetric assay at day 1, 3, and 7. Scanning electron microscopy was used to analyze cell morphology at day 7. Cell differentiation was evaluated assaying alkaline phosphatase (ALP) activity at day 7, 14, and 21. Real-time PCR was used to evaluate the mRNA expression of periostin, ALP, type I collagen, bone sialoprotein and BMP-2. A commercially available enzyme-linked immunosorbent assay was used to assess BMP-2 production. Surface analysis disclosed excellent cell attachment, spread, and penetration into the porous scaffolds. The MTT assay indicated that scaffolds loaded with low concentration of BMP-2 did not influence the viability of cells. Cells grown on the modified scaffolds expressed higher levels of osteogenic markers than the nonmodified scaffolds (p<0.05). Poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds loaded with low-dose BMP-2 exhibited a significant effect stimulating PDL differentiation suggesting a continued evaluation in relevant in vivo models., (© 2014 Wiley Periodicals, Inc.)

Clinical studies have evaluated the effect of conventional periodontal surgical therapy. In general, although some clinical gain in tissue support may be attained, these therapies do not support regeneration of the periodontal attachment. Even though the biological possibility of periodontal regeneration has been demonstrated, the clinical application of this intrinsic potential appears difficult to harness; thus also conceptually most intriguing candidate protocols face clinical challenges. In this review, we explore the bioclinical principles, condiciones sine quibus non, that unleash the innate potential of the periodontium to achieve clinically meaningful periodontal regeneration (i.e. space-provision, wound stability and conditions for primary intention healing). Moreover, limiting factors and detrimental practices that may compromise clinical and biological outcomes are reviewed, as is tissue management in clinical settings., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This study evaluated the effects of drill wear on bone temperature during osteotomy preparation with 3 types of drills and compared heat production between drills. The drills used in this study were titanium nitride-coated metal, tungsten carbide carbon-coated metal, and zirconia ceramic drills. An osteotomy 11 mm in depth was formed in bovine scapular bone following the manufacturer's recommended drill sequences. Drilling was performed without irrigation and repeated 20 times; temperature was measured every 5 times. Next, 200 rounds of drilling during irrigation were performed for each drill, with temperature change monitored until round 200. Analysis of variance statistics were used for analyses of the measured data. Drilling without irrigation showed significant thermal increase at all time points compared to drilling with irrigation (P < .001). No significant difference was found between drill materials. Under irrigation, the frequency of previous drilling had minimal effects on thermal change. The repeated-measures analysis of variance revealed major thermal change at the initial time point (P < .0001), and the multiple comparison tests revealed a significant difference in temperature between the initial drills that had been used 50 or fewer times and those that had been used more than 50 times, irrespective of the drill material. The results of this study indicate that the initial drill should be changed in osteotomy preparation with irrigation after they have been used 50 times. Irrigation may be a more critical factor for the control of temperature elevation than is the drill material.

Purpose: The aim of this systematic review was to evaluate clinical and safety data for recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier when used for alveolar ridge/maxillary sinus augmentation in humans., Materials and Methods: Clinical studies/case series published 1980 through June 2012 using rhBMP-2/ACS were searched. Studies meeting the following criteria were considered eligible for inclusion: >10 subjects at baseline and maxillary sinus or alveolar ridge augmentation not concomitant with implant placement., Results: Seven of 69 publications were eligible for review. rhBMP-2/ACS yielded clinically meaningful bone formation for maxillary sinus augmentation that would allow placement of regular dental implants without consistent differences between rhBMP-2 concentrations. Nevertheless, the statistical analysis showed that sinus augmentation following autogenous bone graft was significantly greater (mean bone height: 1.6 mm, 95% CI: 0.5-2.7 mm) than for rhBMP-2/ACS (rhBMP-2 at 1.5 mg/mL). In extraction sockets, rhBMP-2/ACS maintained alveolar ridge height while enhancing alveolar ridge width. Safety reports did not represent concerns for the proposed indications., Conclusions: rhBMP-2/ACS appears a promising alternative to autogenous bone grafts for alveolar ridge/maxillary sinus augmentation; dose and carrier optimization may expand its efficacy, use, and clinical application., (© 2013 Wiley Periodicals, Inc.)

Background: Application of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been associated with significant adverse events in craniofacial settings, including swelling and seroma formation. Recent work has demonstrated an inverse relationship between bone formation/maturation and rhBMP-2 dose, frequency/severity of adverse events increasing with rising dose., Objective: The objective of this study was to determine the most effective dose for rhBMP-2 soak-loaded onto an absorbable collagen sponge (ACS) carrier for bone formation/maturation using an established defect model., Methods: One hundred sixty-eight outbred male Sprague-Dawley rats, age 11-13 weeks, weight 325-375 g randomized into seven groups of 24 subdivided into groups of eight, were used to provide radiographic and light microscopy observations of bone formation/maturation and aberrant healing events at 2, 4 and 8 weeks following application of rhBMP-2/ACS into critical-size, ø8-mm, through-through, calvarial osteotomy defects for a dose of 1.25, 2.5, 5.0, 10.0 and 20.0 μg rhBMP-2/defect, or serve as ACS or sham-surgery controls., Results: rhBMP-2 dosages ≥ 2.5 μg/defect showed histological defect closure >90% within 2 weeks, and complete resolution within 4 weeks. Adverse healing events including swelling, excessive bone formation or seroma formation could not be determined with certainty in this defect model. Notably ACS control sites showed complete defect closure at the 8-week healing interval., Conclusions: rhBMP-2/ACS accelerates local bone formation in the rat critical-size through-through calvarial defect model once reaching an osteoinductive dose threshold. This threshold may already be reached at a 1.25-/2.5-μg dose in this model. No further enhancement to bone formation/maturation may be observed adding rhBMP-2 above the 2.5-μg dose. The 1.25-20.0 μg dose range did not invoke appreciable aberrant healing events., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Growth/differentiation factor-5 (GDF-5) plays critical roles in mesenchymal cell differentiation and stimulates human periodontal ligament cell proliferation. Potentially, GDF-5 may also play roles in wound healing including periodontal regeneration and alveolar augmentation. The objective of this review was to provide up-to-date information from pre-clinical/clinical studies evaluating GDF-5 for these indications., Methods: A comprehensive search using PubMed and Google search engines was conducted to identify reports on GDF-5 applied to periodontal and alveolar indications. Two reviewers independently screened the titles and abstracts from a total of 479 reports. Full-length articles of 17 pre-clinical and four clinical studies were selected and reviewed., Results: Canine-, porcine- and non-human primate-based models as well as human clinical trials were used in the evaluation of GDF-5 in support of periodontal regeneration and alveolar augmentation. An absorbable collagen sponge (ACS), β-tricalcium phosphate (β-TCP) and a poly(lactic-co-glycolic) acid (PLGA) were evaluated as candidate carriers for GDF-5 using various dose and healing intervals demonstrating significantly enhanced periodontal regeneration/alveolar augmentation including cementum, periodontal ligament and alveolar bone with limited, if any, adverse effects., Conclusion: Growth/differentiation factor-5 supports periodontal regeneration/alveolar augmentation without aberrant healing events documented in qualified pre-clinical models and clinical pilot studies. In perspective, GDF-5 appears a promising technology for periodontal regeneration/alveolar augmentation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1β, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1β enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1β to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1β potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1β potentiates suboptimal BMP-2 (0.5 μg) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0 μg) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1β provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings.

Aim: The aim of this exploratory study was to analyse prevalence of extraction sockets showing erratic healing and evaluate factors potentially impeding healing., Methods: Erratic healing was defined as extraction sites showing clinical observations of fibrous scar tissue occupying the extraction site rather than bone following 12 or more weeks of healing. Computerized tomography was used to evaluate characteristics and calculate Hounsfield unit scores for sites showing erratic healing., Results: A total of 1226 dental records from Seoul National University Dental Hospital archives including patients subject to extractions prior to implant placement were evaluated. Seventy subjects (5.71%) and 97 sites (4.24%) exhibited erratic extraction socket healing. Maxillary incisor/canine sites showed the lowest (0.47%), whereas mandibular molar sites the highest (5.41%) occurrence. In the multivariable analysis, erratic healing was more likely to occur in subjects <60 years old (OR = 2.23, 95%CI = 1.26-3.94), subjects with hypertension (OR = 2.37, 95%CI = 1.24-4.55), in molar sites (OR = 4.91, 95%CI = 1.41-17.07), and following single tooth extractions (OR = 2.98, 95%CI = 1.36-6.53). Computerized tomography showed the highest incidence of bone loss for the buccal wall (49.3%)., Conclusion: Erratic extraction socket healing appears a not uncommon sequel and local factors seem to be major contributors to its occurrence., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Application of growth factors onto dental implant surfaces is being considered to support local bone formation. Bone morphogenetic protein-2 (BMP-2) and BMP-7 have been shown to support local bone formation, but are also associated with adverse events including seroma formation, extensive bone remodeling, and implant displacement captured in the radiographic evaluation. This report presents mineralized tissue formation and associated adverse events following implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) coated onto a purpose-designed titanium porous-oxide implant surface., Material and Methods: Twelve young adult Labrador dogs were used. Three 10-mm titanium implants/jaw quadrant were placed 5 mm into the alveolar ridge in the posterior mandible following surgical extraction of the premolar teeth and reduction of the alveolar ridge. Six animals received implants coated with rhGDF-5 at 30 or 60 μg/implant in contralateral jaw quadrants. Six animals received implants coated with rhGDF-5 at 120 μg/implant or uncoated implants (sham-surgery control) using the same split-mouth design. The mucoperiosteal flaps were advanced, adapted, and sutured to submerge the implants. Radiographic recordings were made immediately postsurgery (baseline), and at week 4 and 8 (end of study). Two masked examiners performed the analysis using computer enhanced radiographic images., Results: rhGDF-5 coated implants displayed mineralized tissue formation significantly exceeding that of the sham-surgery control in a dose-dependent order. The greatest increase was observed for implants coated with rhGDF-5 at 60 μg and 120 μg amounting to approximately 2.2 mm for both groups at 8 weeks. Importantly, none of the implants showed evidence of peri-implant bone remodeling, implant displacement, or seroma formation. The newly formed mineralized tissues assumed characteristics of the resident bone., Conclusions: rhGDF-5 coated onto a titanium porous-oxide implant surface exhibits a dose-dependent potential to stimulate local mineralized tissue formation. Application of rhGDF-5 appears safe as it is associated with limited, if any, adverse events., (© 2012 John Wiley & Sons A/S.)

Aim: To compare the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge carrier (ACS) with autogenous bone graft for augmentation of the edentulous atrophic anterior maxilla., Methods: Twenty-four subjects were enrolled in a randomized, controlled, parallel-group, open-label clinical trial. Subjects either received rhBMP-2/ACS (1.5 mg/ml) or particulated autogenous bone harvested from the mandibular retromolar region. A titanium-mesh was used to provide space and wound stability. A guide was used to standardize clinical recordings using an analogue caliper. Alveolar ridge width was also assessed using cone-beam computed tomography., Results: rhBMP-2/ACS yielded significantly greater radiographic horizontal bone gain compared with autogenous bone graft at immediate subcrestal levels (1.5 ± 0.7 versus 0.5 ± 0.9 mm; p = 0.01); non-significant differences were observed at mid- (2.9 ± 0.8 versus 2.9 ± 0.9 mm; p = 0.98) and apical (1.7 ± 0.9 versus 1.8 ± 1.1 mm; p = 0.85) crestal levels. No significant differences in clinical horizontal bone gain were observed at 6 months between rhBMP-2/ACS and autogenous bone graft (3.2 ± 0.9 mm versus 3.7 ± 1.4 mm; p = 0.31). Sixty-two implants were placed after 6 month of healing with no significant differences between groups for number of implants, implant size, primary stability and survival., Conclusions: rhBMP-2/ACS appears a realistic alternative for augmentation of the edentulous atrophic anterior maxilla., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Previous studies document the therapeutic potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier for indications in the axial and appendicular skeleton. Nevertheless, the ACS does not comprise structural integrity to adequately support bone formation for onlay indications. The objective of this study was to evaluate local bone formation and osseointegration following surgical implantation of rhBMP-2 soak-loaded onto a compression resistant matrix (CRM)., Methods: Routine, contralateral, critical-size, supraalveolar, peri-implant defects in five adult male Hound Labrador mongrel dogs received 0.8 mg rhBMP-2 soak-loaded onto either the ACS (benchmark control) or a CRM (collagen/β-TCP/hydroxyapatite) followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histologic/histometric evaluation., Results: Healing was uneventful albeit considerable initial swelling was observed for either treatment. Sites receiving rhBMP-2/CRM showed significantly increased bone area (20.0 ± 0.9 versus 12.3 ± 2.6 mm(2) , p = 0.03) and bone density (24.1 ± 1.4% versus 14.6 ± 2.0%, p = 0.04) compared with those receiving rhBMP-2/ACS. There were no significant differences between treatments for new bone height and osseointegration. Woven and lamellar trabecular bone lined with abundant osteoid was observed for all sites. Inconsistent cortex formation confirmed the immature nature of the newly formed bone. Seroma formation was observed for both treatments (80-100% of the animals/implants). Sites receiving rhBMP-2/CRM showed residual ceramic granules undergoing biodegradation, including accumulation of foamy macrophages., Conclusions: rhBMP-2/CRM supports bone formation of clinically relevant geometry. Longer observation intervals as well as dose variations appear necessary to capture maturation of the newly formed bone, elimination of residual ceramic granules and resolution of seroma formation(s)., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Application of a synthetic BMP-6 polypeptide in a rat periodontal fenestration defect model enhanced periodontal wound healing/regeneration including new bone and cementum formation. The purpose of this study was to translate the relevance of these initial observations into a discriminating large animal model., Methods: Critical-size (4-5 mm) supraalveolar periodontal defects were created at the 2(nd) and 3(rd) mandibular premolar teeth in 11 Beagle dogs. Experimental sites received BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto an absorbable collagen sponge (ACS) carrier or ACS alone (control) each condition repeated in four jaw quadrants. The animals were euthanized at 8 weeks when block biopsies were collected and processed for histologic/histometric analysis., Results: BMP-6 at 0.25, 1.0 and 2.0 mg/ml soak-loaded onto the ACS yielded significantly enhanced new bone (0.99 ± 0.07 versus 0.23 ± 0.13 mm/BMP-6 at 0.25 mg/ml) and cementum (2.45 ± 0.54 versus 0.73 ± 0.15 mm/BMP-6 at 0.25 mg/ml) formation including a functionally oriented periodontal ligament compared with control (p < 0.05). A significant inverse linear association between BMP-6 dose and new bone (β = -0.21 ± 0.09 mm, p = 0.016) and cementum height (β = -0.34 ± 0.15 mm, p = 0.023) was observed. Minimal root resorption was observed without significant differences between groups. Ankylosis was not observed for any of the experimental groups., Conclusions: Surgical application of BMP-6/ACS onto critical-size supraalveolar defects enhanced periodontal wound healing/regeneration, in particular cementogenesis including a functionally oriented periodontal ligament; the low BMP-6 0.25 mg/ml concentration apparently providing the most effective dose., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The objective of this study is to compare a candidate β-tricalcium phosphate (β-TCP) carrier technology with the absorbable collagen sponge (ACS) benchmark to support recombinant human growth/differentiation factor-5 (rhGDF-5)-stimulated periodontal wound healing/regeneration., Methods: Routine, bilateral, critical-size (5-mm), 1-wall, intrabony periodontal defects were surgically created in the mandibular premolar region in 10 beagle dogs. Five animals received rhGDF-5/β-TCP and five animals received rhGDF-5/ACS, with a total of 20 μg rhGDF-5 per defect. The animals were euthanized for histologic and histometric analyses at 8 weeks postsurgery., Results: Both rhGDF-5/ACS and rhGDF-5/β-TCP stimulated the formation of functionally oriented periodontal ligament, cellular mixed fiber cementum, and woven/lamellar bone. Bone regeneration (height and area) was significantly greater for the rhGDF-5/β-TCP construct than for the rhGDF-5/ACS (3.26 ± 0.30 mm versus 2.22 ± 0.82 mm, P <0.01; and 10.45 ± 2.26 mm(2) versus 5.62 ± 2.39 mm(2), P <0.01, respectively). Cementum formation ranged from 3.83 ± 0.73 mm to 3.03 ± 1.18 mm without significant differences between groups. Root resorption/ankylosis was not observed., Conclusions: The β-TCP carrier technology significantly enhanced rhGDF-5-stimulated bone formation compared with the ACS benchmark in this discriminating periodontal defect model. The structural integrity of the β-TCP carrier, preventing compression while providing a framework for bone ingrowth, may account for the observed results.

In this review, we reflect upon advances and hindrances encountered over the last three decades in the development of strategies for periodontal regeneration. In this soul-searching pursuit we focus on revisiting lessons learned that should guide us in the quest for the reconstruction of the lost periodontium. We also examine beliefs and traditions that should be unlearned so that we can continue to advance the field. This learned/unlearned body of knowledge is consolidated into core principles to help us to develop new therapeutic approaches to benefit our patients and ultimately our society., (© 2013 John Wiley & Sons A/S.)

Aim: The objective of this research was to elucidate early events in periodontal wound healing/regeneration using histological and immunohistochemical techniques., Methods: Routine critical-size, supraalveolar, periodontal defects including a space-providing titanium mesh device were created in 12 dogs. Six animals received additional autologous blood into the defect prior to wound closure. One animal from each group was killed for analysis at 2, 5, 9, 14 days, and at 4 and 8 weeks., Results: Both groups behaved similarly. Periodontal wound healing/regeneration progressed through three temporal phases. Early phase (2-5 days): heterogeneous clot consolidation and cell activation in the periodontal ligament (PDL) and trabecular bone was associated with PDL regeneration and formation of a pre-osteoblast population. Intermediate phase (9-14 days): cell proliferation (shown by PCNA immunostaining)/migration led to osteoid/bone, PDL and cementum formation. Late phase (4-8 weeks): primarily characterized by tissue remodelling/maturation. Fibrous connective tissue from the gingival mucosa entered the wound early, competing with regeneration. By day 14, the wound space was largely filled with regenerative and reparative tissues., Conclusion: Activation of cellular regenerative events in periodontal wound healing/regeneration is rapid; the general framework for tissue formation is broadly outlined within 14 days. Most bone formation apparently originates from endosteally derived pre-osteoblasts; the PDL possibly acting as a supplementary source, with a primary function likely being regulatory/homeostatic. Blood accumulation at the surgical site warrants exploration; supplementation may be beneficial., (© 2012 John Wiley & Sons A/S.)

Background: 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., (© 2012 John Wiley & Sons A/S.)

Objective: Clinical criteria for periodontal wound healing/regeneration include wound stability, space-provision and conditions for primary intention healing. However, wound stability/space-provision may be difficult to obtain in non-contained periodontal defects. The objective of this study was to; using a limited, space-providing device as a conduit, evaluate a concept of space-provision sans tissue occlusion for periodontal wound healing/regeneration., Methods: Bilateral, critical-size, supraalveolar, periodontal defects were created in eight young adult Beagle dogs. One jaw quadrant received a limited, space-providing titanium mesh device, the contra-lateral jaw quadrant served as sham-surgery control followed by submerged wound closure for primary intention healing. The animals were euthanized at 8 weeks for histometric analysis of the surgical sites., Results: Clinical healing was generally uneventful; minor late exposures observed for some defects. Experimental sites exhibited significantly enhanced mean (±SE) bone and cementum regeneration compared with control (1.10 ± 0.20 and 1.32 ± 0.10 mm versus 0.34 ± 0.18 and 0.66 ± 0.15 mm; p < 0.01). A cellular mixed (extrinsic/intrinsic) fibre cementum and functionally oriented collagen fibres were routinely observed. Wound exposures were significantly associated with reduced bone formation (p < 0.05)., Conclusions: Using a limited, space-providing device to support periodontal wound healing/regeneration appears a promising clinical approach for non-contained periodontal defects., (© 2013 John Wiley & Sons A/S.)

Aim: To determine the potential of recombinant human bone morphogenetic protein-2 (rhBMP-2) soak-loaded on to an absorbable collagen sponge (ACS) to induce local bone formation compared with the clinical reference demineralized bone matrix (DBM) and to investigate potential additive/synergistic effects of exogenous parathyroid hormone (PTH)., Methods: Critical-size (8 mm), through-through calvaria osteotomy defects in 160 adult male Sprague-Dawley rats were randomized to receive one of eight interventions: rhBMP-2/ACS, DBM, ACS, or serve as controls (empty defects) combined or not with systemic PTH. Ten animals from each group were followed for 4 and 8 wks for radiographic and histometric analysis. Multivariable analysis was used to assess the effect of experimental intervention and healing time on local bone formation., Results: In the multivariable analysis, rhBMP-2/ACS exhibited significantly greater histologic bone formation than control (β ± SE: 54.76 ± 5.85, p < 0.001) and ACS (β ± SE: 9.14 ± 3.31, p = 0.007) whereas DBM showed significantly less bone formation than control (β ± SE: -32.32 ± 8.23, p < 0.001). Overall, PTH did not show a significant effect on bone formation (β ± SE: 2.72 ± 6.91, p = 0.70). No significant differences in histological defect closure were observed between 4 and 8 wks for all but the control group without PTH., Conclusion: rhBMP-2/ACS significantly stimulates local bone formation whereas bone formation appears significantly limited by DBM. Systemic application of PTH provided no discernible additive/synergistic effects on local bone formation., (Published 2012. This article is a US Government work and is in the public domain in the USA.)

Background: Chinese hamster ovary (CHO) cell-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) has been introduced for spine, long bone, and craniofacial indications. Escherichia coli- (E. coli) derived rhBMP-2 displays comparable efficacy to CHO cell-derived rhBMP-2 in vitro and in small-animal models. The objective of this study is to evaluate the efficacy of E. coli-derived rhBMP-2 compared to the benchmark CHO cell-derived rhBMP-2 using an established large-animal model., Methods: Contralateral, critical-size supraalveolar peri-implant defects in six adult male Hound Labrador mongrel dogs received CHO cell- or E. coli-derived rhBMP-2 (0.2 mg/mL) in an absorbable collagen sponge (ACS) carrier. In each quadrant, three dental implants were placed. A titanium mesh device was used to support space provision. The animals received fluorescent bone markers for qualitative evaluations. Animals were euthanized at 8 weeks for histopathologic and histometric evaluation., Results: Clinical healing included significant swelling, but none of the animals experienced wound dehiscences. CHO cell- and E. coli-derived rhBMP-2 supported comparable bone formation (new bone area, 35.8 ± 3.6 versus 30.1 ± 2.2 mm(2); bone density, 31.8% ± 1.6% versus 35.6% ± 2.5%; and osseointegration, 32.9% ± 7.4% versus 33.7% ± 8.1%) without statistically significant differences between treatments. Newly formed immature delicate trabecular bone in fibrovascular marrow filled the space underneath the titanium mesh and extended coronally above the mesh. Seroma formation was frequently observed. There were no discernable qualitative histologic differences between treatments., Conclusion: CHO cell- and E. coli-derived rhBMP-2 in an ACS carrier appear equally effective at inducing local bone formation in support of dental implant osseointegration.

Background and Objective: A large body of evidence implies that growth and differentiation factors, based on their ability to regulate various functions of cells originating in the periodontal tissues, may support periodontal wound healing/regeneration, creating an environment conducive to and/or immediately inducing de novo tissue formation. This study presents a short systematic overview on growth and differentiation factor technologies evaluated in the clinic for their potential to enhance periodontal wound healing/regeneration., Material and Methods: Reports on growth and differentiation factor technologies evaluated in the clinic for their potential to enhance periodontal wound healing/regeneration were selected for review., Results: Growth and differentiation factor technologies intended for periodontal wound healing/regeneration and evaluated clinically included platelet-derived growth factor, insulin-like growth factor-I and -II, basic fibroblast growth factor, bone morphogenetic protein-3 and growth differentiation factor-5; platelet-derived growth factor was the only Food and Drug Administration-approved commercially available growth and differentiation factor technology. In general, enhanced periodontal regeneration was observed in sites receiving growth and differentiation factors compared with control(s). However, improvements of relatively limited clinical magnitude have been shown thus far., Conclusion: Although growth and differentiation factors project considerable appeal as candidate technologies in support of periodontal wound healing/regeneration, current candidate and commercially available technologies enhance treatment outcomes only to a limited extent in clinical settings., (© 2012 John Wiley & Sons A/S.)

Background: To the best of our knowledge, the influence of external versus internal implant-abutment connections on crestal bone remodeling has not been reported. The aim of the present study is to investigate the influence of the abutment connection on peri-implant crestal bone levels (CBLs) using radiographic recordings., Methods: Radiographic recordings from 40 single-tooth implants (20 external and 20 internal octagonal connections; one implant/patient) in 40 patients (15 males and 25 females; mean age: 54.3 years) were selected for analyses. The radiographic evaluation included the following: 1) linear bone change (LBC); 2) dimensional change (DC); and 3) angle between the implant and adjacent bone (AIB). Differences in LBC, DC, and AIB between implant placement and 1 year after loading for each system were evaluated using a paired t test. Comparison of LBC, DC, and AIB between systems at 1 year after loading was done using analysis of covariance. The significance level was set at P ≤0.05., Results: Radiographic CBLs (LBCs) were reduced at 1 year after loading compared to those at implant placement to reach statistical significance for the external connection (P = 0.000) but not the internal connection (P = 0.939). CBL changes were significantly greater for the external compared to the internal connection (P = 0.000). Similarly, the DC for the external connection was significantly greater compared to that for the internal connection (P = 0.004)., Conclusion: Within the limitations of this study, the implant-abutment connection technology appears to have a significant impact on peri-implant CBLs, with the external connection paralleled by a significant reduction of CBLs.

Background: Ti-6Al-7Nb alloys exhibit enhanced mechanical properties and corrosion resistance and may represent an improvement to present commercially pure (CP) titanium oral implant technology., Objectives: To evaluate crestal remodelling and osseointegration at CP titanium compared with Ti-6Al-7Nb alloy oral implants using a canine model., Methods: Two threaded anodized CP titanium and two Ti-6Al-7Nb alloy anodized oral implants (ø4.5 × 6.1 mm) were placed into each jaw quadrant in the edentulated posterior mandible in six adult male Hound Labrador mongrel dogs. Abutments were placed onto the implants, and the mucogingival flaps were adapted and sutured for transmucosal wound healing. Block biopsies were collected for histometric analysis following an 8-week healing interval., Results: Healing was uneventful. Bone density outside and within the root of the threads averaged (± SE) 49.0 ± 4.5% and 38.7 ± 5.1% for CP titanium implants and 43.2 ± 3.6% and 34.2 ± 4.8% for Ti-6Al-7Nb alloy implants. Mean osseointegration reached 68.0 ± 4.4% and 62.8 ± 2.5% for CP titanium and Ti-6Al-7Nb alloy implants, respectively. Although crestal resorption at lingual sites averaged 0.2 ± 0.1 mm for both technologies, crestal resorption at buccal sites averaged 0.9 ± 0.2 and 1.0 ± 0.6 mm for CP titanium and Ti-6Al-7Nb alloy implants, respectively. There were no statistically significant differences between implant technologies for any parameter assessed. Notably, advanced/advancing buccal crestal resorption exposing the implant threads was observed in 50% of the implants (four of six animals) regardless of implant technology; osteoclastic resorption still observed at 8 weeks following implant placement., Conclusion: Within the limitations of study, anodized Ti-6Al-7Nb alloy implants may represent a feasible alternative to benchmark anodized CP titanium implants. Remodelling of the buccal crestal plate resulting in advanced bone loss appears a major impediment to oral implant osseointegration and possibly, in extension, implant maintenance., (© 2012 John Wiley & Sons A/S.)

To present the safety profile, the early healing phase and the clinical outcomes at 24 weeks following treatment of human intrabony defects with open flap debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier. Twenty chronic periodontitis patients, each with at least one tooth exhibiting a probing depth ≥6 mm and an associated intrabony defect ≥4 mm entered the study. Ten subjects (one defect/patient) were randomized to receive OFD alone (control) and ten subjects OFD combined with rhGDF-5/β-TCP. Blood samples were collected at screening, and at weeks 2 and 24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels, and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on probing, probing depth, clinical attachment level, and radiographs were recorded pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5 plasma levels were detected in any patient. At 6 months, treatment with OFD + rhGDF-5/β-TCP resulted in higher but statistically not significant PD reduction (3.7 ± 1.2 vs. 3.1 ± 1.8 mm; p = 0.26) and CAL gain (3.2 ± 1.7 vs. 1.7 ± 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration, the use of rhGDF-5/β-TCP appeared to be safe and the material possesses a sound biological rationale. Thus, further adequately powered, randomized controlled clinical trials are warranted to confirm the clinical relevance of this new approach in regenerative periodontal therapy. rhGDF-5/β-TCP may represent a promising new techology in regenerative periodontal therapy.

Objective: The aim of this study was to evaluate long-term (24 weeks) alveolar bone maturation following surgical application of recombinant human growth/differentiation factor-5 (rhGDF-5) in an injectable poly-lactide-co-glycolide-acid (PLGA) composite carrier using an established periodontal defect model., Methods: Routine, bilateral, 4 × 5 mm (width × depth), 1-wall, critical-size, intra-bony periodontal defects were surgically created at the 2nd and 4th mandibular premolar teeth in 10 Beagle dogs. The animals were randomized to receive (split-mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF-5/PLGA high dose (188 μg/defect) versus sham-surgery control (5 animals), and rhGDF-5/PLGA low dose (37 μg/defect) versus carrier control (5 animals). The animals were euthanized for histometric analysis following a 24-week healing interval., Results: Clinical healing was uneventful. The rhGDF-5 high dose significantly increased bone formation compared with controls in terms of bone area (p < 0.05), and a high degree of bone maturation was observed in the rhGDF-5/PLGA high dose group. Root resorption/ankylosis or other aberrant healing events were not observed., Conclusion: The rhGDF-5/PLGA appears to support alveolar bone healing/regeneration and the rhGDF-5/PLGA high dose uniquely increased maturation of the regenerated bone., (© 2012 John Wiley & Sons A/S.)

Objective: Although a previous study reported that recombinant human growth/differentiation factor-5 (rhGDF-5) coated onto a β-tricalciumphosphate (β-TCP) significantly enhanced periodontal regeneration, the long-term stability/maturation of the regenerated tissues has not been demonstrated. The objective of this study was to evaluate periodontal regeneration/maturation following application of rhGDF-5/β-TCP using an established periodontal defect model and a 24-week healing interval., Material & Methods: Unilateral, surgically created, 4 × 4 × 5 mm (length × width × height), one-wall, critical-size, intra-bony periodontal defects at the mandibular second and fourth premolar teeth in five young adult Beagle dogs received rhGDF-5/β-TCP. Bilateral sites at the fourth premolar in the other four dogs served as pristine controls receiving mucogingival flap surgery without defect induction. The animals were euthanized at 24 weeks for histological analysis. Unpublished data from the previous 8-week study were used to compare tissue maturation between 8 and 24 weeks., Results: Linear histometric observations of cementum and alveolar regeneration showed no significant differences between the 8- and 24-week observation intervals. However, parameters of periodontal tissue maturation showed significant differences between the observation intervals including increased fraction mineralized tissue and lamellar bone (p < 0.05) and decreased osteocyte counts (p < 0.05) at 24 weeks compared with 8 weeks. Although the count inserting Sharpey's fibre did not significantly change, regenerated cementum remote from the intact periodontal ligament appeared more highly mineralized and thicker at 24 weeks compared with 8 weeks, and compared with the pristine cementum. Minimal β-TCP remained., Conclusions: These 24-week observations suggest that regenerated periodontal tissues in sites receiving rhGDF-5/β-TCP undergo progressive maturation without debilitating aberrant tissue reactions., (© 2012 John Wiley & Sons A/S.)

Background and Objective: Osteoactivin is a novel glycoprotein shown to exhibit an important role in regulating osteoblast differentiation and function. The aim of the present study was to evaluate the potential of osteoactivin to support bone regeneration using an established defect model., Material and Methods: Critical-size, 8-mm-diameter through-and-through calvarial osteotomy defects were created in 60 adult male Sprague-Dawley rats. Test animals received 0.1 mL of osteoactivin in phosphate-buffered saline (50 μg/mL) soak-loaded onto an absorbable collagen sponge. Controls received 0.1 mL of phosphate-buffered saline soak-loaded onto the absorbable collagen sponge or no further intervention (sham-surgery). The animals were euthanized 2 and 4 wk after treatment and histometric analyses were performed., Results: The absorbable collagen sponge control (mean ± standard deviation: 40.9 ± 26.9%) showed borderline significant greater bone fill compared with sham-surgery (22.9 ± 15.8%; p = 0.10) and osteoactivin (20.2 ± 11.8%; p = 0.07) treatments at 2 wk. In contrast, osteoactivin (84.7 ± 15.8%) showed significantly greater bone fill than sham-surgery (28.4 ± 9.6%; p < 0.001) and absorbable collagen sponge (41.8 ± 22.1%; p < 0.001) at 4 wk. No animals receiving sham-surgery or absorbable collagen sponge exhibited complete bone fill at 4 wk while 70% of the animals receiving osteoactivin showed complete bone fill., Conclusion: Osteoactivin demonstrates a significant potential to support bone regeneration/formation. Studies using discriminating large animal models are necessary to explore clinical application for periodontal and craniofacial indications., (© 2011 John Wiley & Sons A/S.)

Aim: The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate β-tricalcium phosphate (β-TCP) carrier rhGDF-5/β-TCP into periodontal defects in man., Material & Methods: Twenty chronic periodontitis patients, each with at least one tooth scheduled for extraction exhibiting a probing depth ≥6 mm and an associated intra-bony defect ≥4 mm participated in the study upon written informed consent. Subjects (one defect/patient) were randomized to receive open flap debridement (OFD) + rhGDF-5/β-TCP (n = 10) or OFD alone (control; n = 10). Block biopsies of the defect sites were collected at 6 months post-surgery and prepared for the histological evaluation. Two masked examiners evaluated the deepest aspect of each defect site relative to bone (height/area), periodontal ligament (PDL) and cementum regeneration, and residual β-TCP., Results: Sites receiving rhGDF-5/β-TCP showed numerically greater PD reduction (3.7 ± 1.2 versus 3.1 ± 1.8 mm; p = 0.26), less gingival recession (0.5 ± 0.8 versus 1.4 ± 1.0 mm; p < 0.05) and greater clinical attachment level (CAL) gain (3.2 ± 1.7 versus 1.7 ± 2.2 mm; p = 0.14) at the deepest aspect of the defect compared with OFD alone. One biopsy in the rhGDF-5/β-TCP and four biopsies in the OFD group were deemed as not evaluable. Histologically, bone regeneration height was almost threefold greater for the rhGDF-5/β-TCP treatment compared with OFD alone (2.19 ± 1.59 versus 0.81 ± 1.02 mm; p = 0.08). Similarly an almost twofold increase was observed for PDL (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26), cementum (2.16 ± 1.43 versus 1.23 ± 1.07 mm; p = 0.26) and bone regeneration area (0.74 ± 0.69 versus 0.32 ± 0.47 mm(2) ; p = 0.14). Root resorption/ankylosis was not observed. Residual β-TCP occupied 8.4 ± 11.5% of the area of interest in biopsies of patients receiving rhGDF-5/β-TCP. Five biopsies (one rhGDF-5/β-TCP, four OFD) were deemed unsuitable to allow a meaningful histological or histometrical evaluation., Conclusions: Descriptive statistics showed greater PD reduction and CAL gain, and greater alveolar bone regeneration and periodontal regeneration at sites that received rhGDF-5/β-TCP compared to control. However, these differences were not statistically significant. Future studies with larger sample sizes will have to be conducted to verify these findings., (© 2011 John Wiley & Sons A/S.)

Objectives: The objective of this study was to evaluate the effect of drill-bone contact area on bone temperature during osteotomy preparation., Material and Methods: Conventional triflute Ø3.6 mm drills were modified with the intent to reduce frictional heat induction. The peripheral dimensions of the drill were reduced 0.15, 0.35 and 0.5 mm to evaluate the effect of surface area on induction of frictional heat between the drill and bone/cutting debris (parameter A). Also, the lateral cutting surface of the drill was set to 0.1, 2 and 7.5 mm to estimate heat induced by direct function of the drill (parameter B). A non-modified triflute drill (parameter A: 0 mm; parameter B: 15 mm) served as control. Thus, nine drills with different A/B combinations vs. one control were tested in artificial bone. Real-time temperature changes (during drilling and withdrawing) were assessed using an infrared thermal imager. Each drilling procedure was performed up to 20 times. Thermal image data were transferred to a PC for simultaneous analysis., Results: Mean temperature changes for all modified drill combinations were smaller than for the control (P<0.001). The effects of parameters A and B were statistically significant (P<0.001). There was a significant interaction effect between the two parameters (P<0.001) showing that the effect of parameter A on the mean temperature changes is different depending on the values of parameter B. As the dimensions of parameter B decreased, the temperature change during drilling also decreased. However, a tendency for the temperature to increase or decrease by parameter A was not observed., Conclusions: Within the limitations of this pilot study, the observations herein suggest that reduction in contact area between the drill and bone reduces heat induction. Further studies to optimize drill/bone contact dimensions are needed., (© 2010 John Wiley & Sons A/S.)

Purpose: To evaluate osseointegration of a novel calcium phosphate (CaP)-coated titanium porous oxide implant surface., Materials and Methods: Twenty adult male New Zealand White rabbits were used. Each animal received two titanium porous oxide-surfaced implants (benchmark control: TiUnite, Nobel Biocare) and two novel CaP-coated titanium porous oxide-surfaces implants; they were randomly allocated to contralateral tibia implant sites. The animals were sacrificed after 2 or 4 weeks, and tissues were evaluated histometrically., Results: Healing was generally uneventful. A removal torque analysis showed significantly higher mean (± SE) peak values for the control implants than for the test implants at 2 weeks (31.4 ± 2.5 Ncm versus 20.4 ± 1.8 Ncm) and 4 weeks (48.4 ± 5.5 Ncm versus 30.3 ± 3.9 Ncm). Light microscopy showed no significant differences in local bone density around control and test implants at 2 and 4 weeks (range, 85% to 91% within the thread area and 91% to 95% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 81.8% ± 2.8% and 75.7% ± 4.6%, respectively, and at 4 weeks the bone-implant contact values were 79.4% ± 2.8% and 73.5% ± 4.2%, respectively; these differences were not significant. Backscatter scanning electron microscopy also showed no significant differences in local bone density at control and test implants at 2 and 4 weeks (range, 55% to 72% within the thread area and 75% to 81% immediately outside the threads). At 2 weeks, bone-implant contact for control and test implants averaged 66.4% ± 2.9% and 61.5% ± 5.1%, respectively, and at 4 weeks mean values were 60.1% ± 4.2% and 53.3% ± 4.6% (differences not significant)., Conclusions: The results suggest that the novel CaP-coated surface effectively supports osseointegration.

Objective: The purpose of this study was to evaluate the effect of recombinant human growth/differentiation factor-5 (rhGDF-5) on periodontal wound healing/regeneration using an injectable poly-lactide-co-glycolide-acid (PLGA) composite carrier and an established defect model., Methods: Bilateral 4 × 5 mm (width × depth) one-wall, critical-size, intra-bony periodontal defects were surgically created at the second and the fourth mandibular pre-molar teeth in 15 Beagle dogs. The animals were randomized to receive (using a split-mouth design; defect sites in the same jaw quadrant getting the same treatment) rhGDF-5 high dose (188 μg/defect) versus sham-surgery control (five animals), rhGDF-5 mid dose (37 μg/defect) versus carrier control (five animals), and rhGDF-5 low dose (1.8 μg/defect) versus treatment reported elsewhere (five animals). The animals were euthanized for histometric analysis following an 8-week healing interval., Results: Clinical healing was uneventful. The rhGDF-5/PLGA construct was easy to assemble and apply. The rhGDF-5 high dose supported significantly increased bone formation compared with the low-dose, sham-surgery, and carrier controls (p<0.05) and induced significantly increased cementum formation compared with the controls (p<0.05). Root resorption/ankylosis or other aberrant healing events were not observed., Conclusion: rhGDF-5 appears to effectively support periodontal wound healing/regeneration in a dose-dependent order; the PLGA composite appears to be an effective ease-of-use candidate for carrier technology., (© 2011 John Wiley & Sons A/S.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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.

The authors identified no report describing implant primary stability obtained by external fixation as a means to achieve osseointegration in craniofacial settings. This article describes a situation in which an implant was placed without direct contact with the resident bone; primary stability was provided by an external device. An edentulous patient was restored with 5 endosseous titanium implants to support a mandibular fixed prosthesis. An implant placed in the right central incisor position was removed after 48 hours and replaced with a shorter and narrower implant without contact with resident bone. Thus, primary stability for the implant was provided by rigid fixation to the prosthesis rather than by bone anchorage. At recall examinations after 6 and 27 months, all implants, including the implant in the right central incisor position, showed clinical and radiographic signs of osseointegration. Resonance frequency analysis indicated acceptable stability and osseointegration for all implants. Observations of this patient suggest that implant osseointegration can be achieved by providing primary stability using a fixed complete denture. Primary bone anchorage/contact does not appear to be critical to the osseointegration process., (Copyright © 2010 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.)

Background: To our knowledge, no study has evaluated the success or survival rate of single-tooth implants that replaced missing maxillary and mandibular second molars. The purpose of the present study was to evaluate the 1- to 5-year cumulative survival rate (CSR) for single-tooth implants placed in the second molar region and the effects of associated factors., Methods: Four hundred eighty-nine patients (298 males and 191 females; age range: 23 to 91 years; mean age: 47 years) who were admitted to the Seoul National University Dental Hospital between March 2003 and July 2008 and treated with single-tooth implants in the second molar region (227 maxillary implants and 294 mandibular implants; total: 521 implants) were included in the study. Thirty-two subjects received two implants each. A 1- to 5-year CSR was calculated using a life-table analysis. A comparison of CSRs between maxillary versus mandibular implants, one-stage versus two-stage implants, short (10 mm) implants, and standard-diameter (or=5.0 mm) implants was performed using Wilcoxon (Gehan) statistics. P <0.05 was considered significant., Results: Fifteen of the 521 implants were lost between insertion and the follow-up examinations. The 1- to 5-year CSR was 95.1%. There were no statistically significant differences in CSRs between implants placed in maxillas and mandibles (96.3% versus 94.9%, respectively; P = 0.084), one- and two-stage implants (95.6% versus 94.7%, respectively; P = 0.267), short and long implants (100% versus 95.1%, respectively; P = 0.582), and standard- and wide-diameter implants (93.8% versus 96.8%, respectively; P = 0.065)., Conclusions: Within the limitations of the study, the placement of single-tooth implants in the second molar region was an effective and reliable treatment modality. Also, associated factors such as implant diameter, length, and location (the maxilla versus the mandible) may not have an impact on the long-term success of implants.