Enzyme-Responsive Nanoparticles for Dexamethasone Targeted Delivery to Treat Inflammation in Diabetes.

Diabetes is a global epidemic accompanied by impaired wound healing and increased risk of persistent infections and resistance to standard treatments. Therefore, there is an immense need to develop novel methods to specifically target therapeutics to affected tissues and improve treatment efficacy. This study aims to use enzyme-responsive nanoparticles for the targeted delivery of an anti-inflammatory drug, dexamethasone, to treat inflammation in diabetes. These nanoparticles are assembled from fluorescently-labeled, dexamethasone-loaded peptide-polymer amphiphiles. The nanoparticles are injected in vivo, adjacent to labeled collagen membranes sub-periosteally implanted on the calvaria of diabetic rats. Following their implantation, collagen membrane resorption is linked to inflammation, especially in hyperglycemic individuals. The nanoparticles show strong and prolonged accumulation in inflamed tissue after undergoing a morphological switch into microscale aggregates. Significantly higher remaining collagen membrane area and less inflammatory cell infiltration are observed in responsive nanoparticles-treated rats, compared to control groups injected with free dexamethasone and non-responsive nanoparticles. These factors indicate improved therapeutic efficacy in inflammation reduction. These results demonstrate the potential use of enzyme-responsive nanoparticles as targeted delivery vehicles for the treatment of diabetic and other inflammatory wounds.

Addition of Resolvins D1 or E1 to Collagen Membranes Mitigates Their Resorption in Diabetic Rats.

Uncontrolled diabetes is characterized by aberrant inflammatory reactions and increased collagenolysis. We have reported that it accelerates the degradation of implanted collagen membranes (CM), thus compromising their function in regenerative procedures. In recent years, a group of physiological anti-inflammatory agents called specialized pro-resolving lipid mediators (SPMs) have been tested as a treatment for various inflammatory conditions, either systemically or locally, via medical devices. Yet, no study has tested their effect on the fate of the biodegradable material itself. Here, we measured the in vitro release over time of 100 or 800 ng resolvin D1 (RvD1) incorporated into CM discs. In vivo, diabetes was induced in rats with streptozotocin, while buffer-injected (normoglycemic) rats served as controls. Resolvins (100 or 800 ng of RvD1 or RvE1) were added to biotin-labeled CM discs, which were implanted sub-periosteally over the calvaria of rats. Membrane thickness, density, and uniformity were determined by quantitative histology after 3 weeks. In vitro, significant amounts of RvD1 were released over 1-8 days, depending on the amount loaded. In vivo, CMs from diabetic animals were thinner, more porous, and more variable in thickness and density. The addition of RvD1 or RvE1 improved their regularity, increased their density, and reduced their invasion by the host tissue significantly. We conclude that addition of resolvins to biodegradable medical devices can protect them from excessive degradation in systemic conditions characterized by high degree of collagenolysis.

Single-cell transcriptomic analysis of oral masticatory and lining mucosa-derived mesenchymal stromal cells.

AIM: To reveal the heterogeneity of ex vivo-cultured human mesenchymal stromal cells derived from either masticatory or lining oral mucosa. MATERIALS AND METHODS: Cells were retrieved from the lamina propria of the hard palate and alveolar mucosa of three individuals. The analysis of transcriptomic-level differences was accomplished using single-cell RNA sequencing. RESULTS: Cluster analysis clearly distinguished between cells from the masticatory and lining oral mucosa, and revealed 11 distinct cell sub-populations, annotated as fibroblasts, smooth muscle cells or mesenchymal stem cells. Interestingly, cells presenting a mesenchymal stem cell-like gene expression pattern were predominantly found in masticatory mucosa. Although cells of masticatory mucosa origin were highly enriched for biological processes associated with wound healing, those from the lining oral mucosa were highly enriched for biological processes associated with the regulation of epithelial cells. CONCLUSIONS: Our previous work had shown that cells from the lining and masticatory oral mucosae are phenotypically heterogeneous. Here, we extend these findings to show that these changes are not the result of differences in averages but rather represent two distinct cell populations, with mesenchymal stem cells more common in masticatory mucosa. These features may contribute to specific physiological functions and have relevance for potential therapeutic interventions.

Histologic and Histomorphometric Evaluation of a Connective Tissue Graft Retrieved with a Novel Deepithelialization Procedure: A Case Series.

Various free connective tissue graft (CTG) harvesting techniques have been reported. The lining epithelium of the palatal graft may be retrieved either intra- or extraorally. This report presents a series of root coverage cases where deepithelialization was intraorally performed before harvesting the graft with a round diamond bur mounted on a low-speed handpiece. Ten single-tooth gingival recession defects in five patients were treated, applying a surgical procedure based on a coronally advanced flap combined with a free CTG that was deepithelialized in situ by the same method. Recession and probing depths and keratinized tissue and recession widths were recorded at baseline and the follow-up evaluations. Follow-up was between 7 and 21 months (mean: 12.1 ± 5.04 months). Clinical, esthetic, and histologic evaluations were performed. Mean root coverage was 89% ± 24.86% (range: 25% to 100%), and complete root coverage was observed in 80% of cases; the esthetic score range was 6 to 9 (mean: 7.44 ± 1.01). Epithelial remnants, although different in proportions, were evident in all samples (range of prevalence: 4.57% to 29.12%). Within the limitations of the small number of clinical cases, the presented in situ deepithelialization technique for CTG seems to be valuable and may accordingly be routinely applied.

Fibroblasts from the oral masticatory and lining mucosa have different gene expression profiles and proliferation rates.

AIMS: To compare the gene expression profiles and proliferation rates of fibroblasts from the oral lining and masticatory mucosae. MATERIALS AND METHODS: Primary human fibroblasts were retrieved from the posterior masticatory hard palate and the lining alveolar mucosa of five individuals. The gene expression profile was evaluated using total RNA sequencing. The proliferation rate was determined colorimetrically. RESULTS: Substantial differences in specific gene groups and pathways were observed between fibroblasts from the two tissues. Significantly enriched gene ontology processes were focused on the extracellular components. Lining mucosa fibroblasts exhibited significantly higher expression of the principal structural collagens, cranial neural crest markers, and homeobox genes associated with positional memory. Masticatory mucosa fibroblasts showed greater expression of genes related to transforming growth factor-ß signalling, which may be associated with fibrosis. In addition, they expressed higher levels of the EP2 prostaglandin E2 receptor and Toll-like receptor 1. Finally, masticatory mucosa fibroblasts exhibited a 10%-30% higher proliferation rate. CONCLUSIONS: Fibroblasts from the lining and masticatory oral mucosae are phenotypically heterogeneous, presenting distinct gene expression profiles and proliferation rates. These features may contribute to their specific physiological functions and have relevance for potential therapeutic applications.

Effect of root surface conditioning on gingival recession coverage with a connective tissue graft. A retrospective comparative study of three different agents.

OBJECTIVE: Different root modifiers have been proposed in the literature with an attempt to improve the healing process and the success rate of root coverage procedures. The aim of the present retrospective study was to evaluate the effect of three different types of root surface conditioning, namely, tetracycline (TTC), ethylene-di-amino-tetra-acetic acid (EDTA) and saline, on the outcome of root coverage procedures applying the same surgical technique. MATERIALS AND METHODS: Twenty-nine patients with 60 Classes I, II, or III recession defects were treated using connective tissue with a partial-thickness double-pedicle graft. In 21 recession defects root surface was treated with TTC and, in other 21, with EDTA, while in the remaining, saline solution was applied. Statistical analysis consisted of descriptive statistics and Kruskal-Wallis, Mann-Whitney, and chi-square tests. RESULTS: Differences between pre- and postoperative values were statistically significant only within but not between groups. Mean root coverage was 73.25%, 69.19%, and 82.17% in the TTC, the EDTA, and the saline groups, respectively. The study revealed no statistically significant differences for all evaluated parameters between groups. CONCLUSION: Within the limits of this study, root conditioning, prior to root coverage procedures, does not significantly affect their outcome. CLINICAL SIGNIFICANCE: Clinical outcome of root coverage procedures is not related to the type of root surface conditioning.

Porphyromonas gingivalis lipopolysaccharide and glycated serum albumin increase the production of several pro-inflammatory molecules in human gingival fibroblasts via NFκB.

OBJECTIVE: Diabetes increases the incidence/severity of periodontal diseases by inducing a chronic inflammation, driven by accumulation of AGEs (advanced glycation end products). We tested whether glycated human serum albumin (G-HSA, a form of AGE), representing a diabetic state, augments the pro-inflammatory response of human gingival fibroblasts (hGFs) to a bacterial challenge (Porphyromonas gingivalis Lipopolysaccharide (LPS)). METHODS: Primary hGFs were incubated with LPS (0.5-5 µg/mL) and G-HSA (50-200 µg/mL) and the production and gene expression of IL-1ß, IL-6, IL-8, MMP-1, MCP-1, and TNFα were analyzed by Magnetic Luminex Assay and real-time PCR, respectively. Non-glycated serum albumin (HSA) served as negative control. Cytotoxicity of the 2 agents was tested with an XTT assay. NFκB activation (p65 phosphorylation) was measured with an ELISA. RESULTS: P. gingivalis LPS and G-HSA were not toxic to hGFs and increased the amount of MMP-1, MCP-1, IL-6, and IL-8, (but not TNFα and IL-1ß) secreted into the medium at 24 h. Control HSA had no effect. Many LPS/G-HSA combinations displayed a synergistic stimulation of these molecules. Both agents increased mRNA levels of these 4 molecules at 6 h, 12 h or both (IL-6). NFκB activation at 6 h was caused by both agents with a possible synergism at the higher concentrations. CONCLUSIONS: glycated albumin augments the pro-inflammatory response of human gingival fibroblasts to P. gingivalis LPS. Thus, AGE accumulation in diabetes could aggravate periodontal inflammation by augmenting the pro-inflammatory response of host GFs to P. gingivalis, a well-recognized periopathogenic bacteria.

Dental implant placement is a possible risk factor for the development of multiple cracks in non-endodontically treated teeth.

The objective of this study was to evaluate potential risk factors, including the placement of dental implants, for the development of tooth cracks. A series of 212-patients, who were referred for endodontic treatment, were retrospectively screened, of which 72 (34%) patients had been diagnosed with 80-cracked teeth confirmed with an operating microscope. These patients had an average age of 53-years and were equally distributed between genders. Forty-one percent of the cracked teeth were diagnosed after the placement of dental implants, with an average of 3-implants per patient. Seventy percent of the cracks were diagnosed more than 1-year after implant loading. Implant placement was associated with higher odds of having multiple cracks (OR = 9.78, CI:2.320, 41.216)(p < 0.05). The proportion of cracked premolars was relatively high (30%), and most cracked teeth (79%) were vital and with a normal periapical diagnosis (86%). Most cracked teeth (71%) had an amalgam restoration, and teeth restored with amalgam were at a higher risk of having multiple cracks (p < 0.05). Clinicians should be aware of a common profile of endodontic patients with multiple cracks in a non-endodontically treated premolar, restored with an amalgam restoration, which was diagnosed with the cracks more than 1-year after reconstruction utilizing multiple implants.

Accelerated degradation of collagen membranes in type 1 diabetic rats is associated with increased expression and production of several inflammatory molecules.

BACKGROUND: Membrane durability is critical for regenerative procedures. We reported previously that type 1-like diabetes in rats accelerates the degradation of collagen membranes and we tested here whether this is associated with increased local production of inflammatory molecules as part of a diabetes-induced chronic inflammation around and within the membranes. METHODS: Collagen membrane discs were implanted under the scalp in diabetic (streptozotocin-induced) and control rats, which were sacrificed after 2 or 3 weeks. Total RNA and proteins were isolated from the membrane and its surrounding tissues and the expression and production of six inflammatory molecules (interleukin-6 [IL-6], tumor necrosis factor alpha [TNFα], matrix metalloproteinase [MMP]-9, macrophage migration inhibitory factor [MIF], MIP-1α, and MIP-2α) was measured using real-time PCR and western blotting, respectively. Minimal histological analysis of the membranes was conducted to conform to previous studies. RESULTS: Hyperglycemia resulted in reduced membrane thickness (by 10% to 25%) and increased mononuclear infiltrate inside the membrane. mRNA and protein levels of IL-6, TNFα, and MMP-9 were elevated in diabetic rats both 2 and 3 weeks post-surgery. The levels (both mRNA and protein) of MIF were increased at 2 weeks post-surgery and those of MIP-1α and MIP-2α at 3 weeks. There was a very good match in the temporal changes of all examined genes between the mRNA and protein levels. CONCLUSIONS: Elevated local production of inflammatory cytokines and MMPs, together with apparent mononuclear infiltrate and increased collagenolysis confirm that hyperglycemia leads to a chronic inflammation in and around the implanted collagen membranes, which reduces membrane longevity.

Modified Tunnel Double Papilla Procedure for Root Coverage in the Anterior Mandible.

Free connective tissue grafts, barrier membranes, pedicle flaps, soft tissue allografts, and xenografts have been described for root coverage and augmenting the zone of attached gingiva. The present report evaluated a modified tunnel surgical procedure for root coverage of mandibular anterior teeth where a connective tissue graft was combined with a tunnel and double papilla flap. Fourteen patients with 18 consecutive Miller Class I or II gingival recession defects in the anterior mandible were treated with a connective tissue graft combined with a tunnel and double papilla flap procedure. The following parameters were recorded at baseline and every 6 months postsurgery for up to 19 months: probing depth (PD), vertical recession dimension (RD), keratinized tissue width (KT), and recession width (RW). Statistical analysis consisted of descriptive statistics, analysis of variance with repeated measures, and t test. Statistical analysis proved significant differences between pre- and postoperative values. Mean percentage of root coverage was 83.28% (standard deviation: 22.897), while complete root coverage was obtained in 55% of sites. Baseline values differed between Class I and II recession defects. Clinical attachment level gain, KT gain, and amount of root coverage were statistically significantly larger in Class II defects, while the degree of residual recession and percentage of root coverage were similar in both recession classes. A statistically significant interaction between recession class, independent variable, and pre- and postoperative vertical recession defects (dependent variables) was recorded (P = .004). Within the limitations of the sample size, the reported procedure showed predictable root coverage with color match combined with an increased zone of keratinized tissue.

Combination Therapy for Reconstructive Periodontal Treatment in the Lower Anterior Area: Clinical Evaluation of a Case Series.

Clinically, periodontal regeneration may be achieved by the application of barrier membranes, grafts, wound-healing modifiers, and their combinations. Combination therapy refers to the simultaneous application of various periodontal reconstructive treatment alternatives to obtain additive effects. This approach may lead to assemblage of different regenerative principles, such as conductivity and inductivity, space provision and wound stability, matrix development and cell differentiation. The application of autogenous connective tissue grafts during periodontal regenerative treatment with enamel matrix proteins derivative (EMD) has been previously reported. The present case series present a modified approach for treatment of severe periodontally involved lower incisors presenting with thin gingival biotype, gingival recession, minimal attached and keratinized gingiva width and muscle and/or frenum pull. In all cases a combination therapy consisting of a single buccal access flap, root conditioning, EMD application on the denuded root surfaces and a free connective tissue graft was performed. Clinical and radiographic outcomes were consistently satisfactory, leading to probing depth reduction, clinical attachment gain, minimal gingival recession, increased attached and keratinizing gingival width, elimination of frenum and/or muscle pull together with radiographic bone fill of the defects. It may be concluded that the present combination therapy for reconstructive periodontal treatment in the lower anterior area is a valuable alternative for indicated cases.

Extended Maxillary Sinus Augmentation to the Apical Area of the Neighboring Teeth: Advantages and Limitations.

The extension of sinus floor augmentation beyond the edentulous area, apical to the adjacent teeth, has many therapeutic advantages, but the reliability and safety of the procedure has not been assessed in depth. The present study compares the gain of bone anterior and posterior to the edentulous area and evaluates potential advantages and limitations in the clinical setting. The maximum vertical bone height in the edentulous and extended maxillary sinus augmentation (EMSA) areas and the thickness of the sinus membrane of 65 patients were measured. Those measurements were analyzed using the t test and Pearson correlations. The average vertical bone gain was 11.98 ± 3.53 mm in the edentulous sinus area and 8.60 ± 3.89 mm in the EMSA area (P < .05). Minor perforations of the sinus membrane occurred in 4 patients. There were no postsurgical graft contaminations or periradicular changes during follow-up. EMSA is a reliable and safe procedure with a very low complication rate. This approach is effective and safe for patients who have lost part of their posterior dentition. It enables future implant placement while avoiding the need for sinus reentry and proximal teeth extraction.

Soft and Hard Tissue Regeneration-A Special Issue of Dentistry Journal.

This Special Issue entitled "Soft and Hard Tissue Regeneration" will cover both periodontal and implant therapies.[...].

Lateral bone augmentation in narrow posterior mandibles, description of a novel approach, and analysis of results.

BACKGROUND: Combination of particulate grafts and collagen membranes is widely used for augmentation of bony defects for implant placement. Fixation of the barrier membrane may avoid complications due to unfavorable mechanical properties and poor stability leading to collapse of the augmented area. PURPOSE: To evaluate a new simplified method for resorbable collagen membrane fixation in lateral bone augmentation procedures in narrow posterior mandibles. MATERIALS AND METHODS: This retrospective study analyzed 16 procedures performed in 15 patients who followed lateral ridge augmentation procedures before implant placement in the posterior mandible. A particulate mineralized bone allograft was covered with a cross-linked resorbable collagen barrier membrane, which was fixated with a single, nonresorbable pin. Complications were registered and results analyzed on pre and post op measurements on computerized tomographic scans. Descriptive statistical analysis and ANOVA with repeated measures were performed. RESULTS: No complications were recorded. Average bone gain was 3.3 mm at implant platform level and 4.29 mm at 3 mm apically, both, statistically significant. All sites had sufficient bone width allowing implant placement. Thirty-three implants placed in the augmented areas, integrated and survived for over a 2-year follow-up. CONCLUSION: The simplified membrane fixation procedure enables large horizontal bone gain with minimal complications while allowing adequate implant placement.

Tetracycline impregnation affects degradation of porcine collagen matrix in healthy and diabetic rats.

OBJECTIVES: The present study evaluated the degradation of collagen matrix (CM) immersed in tetracycline (TTC) or phosphate-buffered saline (PBS) in diabetic and normoglycemic rats. MATERIALS AND METHODS: Diabetes was induced in 15 rats by systemic streptozotocin (STZ) (experimental); 15 healthy rats served as controls. One day before implantation 60 CM disks, 5 mm in diameter, were labeled with biotin: 30 were immersed in tetracycline (TTC) and 30 in PBS. One disk of each type was implanted subdermally in each rat. Animals were euthanized after 3 weeks, and tissue specimens containing the disks were prepared for histologic analysis. Horseradish peroxidase (HRP)-conjugated streptavidin was used to detect the remaining biotinylated collagen. Residual collagen area within the CM disks was analyzed and compared to baseline. RESULTS: Diabetes significantly increased the CM degradation. Immersion of the CM disks in a 50-mg/mL TTC solution before implantation decreased its degradation both in diabetic and normoglycemic rats. CONCLUSIONS: Diabetes significantly increases collagen matrix degradation; immersion of collagen matrix in TTC before implantation decreases its degradation in both diabetic and normoglycemic conditions. CLINICAL RELEVANCE: Immersion of medical collagen devices in TTC may be an effective means to decrease their resorption rate and increase their effectiveness, especially in situations with increased degradation such as diabetes.

In vitro models for evaluation of periodontal wound healing/regeneration.

Periodontal wound healing and regeneration are highly complex processes, involving cells, matrices, molecules and genes that must be properly choreographed and orchestrated. As we attempt to understand and influence these clinical entities, we need experimental models to mimic the various aspects of human wound healing and regeneration. In vivo animal models that simulate clinical situations of humans can be costly and cumbersome. In vitro models have been devised to dissect wound healing/regeneration processes into discrete, analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range from simple culture of cells grown in monolayers and exposed to biological modulators or physical effectors and materials, to models in which cells are 'injured' by scraping and subsequently the 'wound' is filled with new or migrating cells, to three-dimensional models of epithelial-mesenchymal recombination or tissue explants. The cells employed are gingival keratinocytes, fibroblasts or endothelial cells, and their proliferation, migration, attachment, differentiation, survival, gene expression, matrix production or capillary formation are measured. Studies of periodontal regeneration also include periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors, and cementoblasts. Regeneration models measure cellular proliferation, attachment and migration, as well as gene expression, transfer and differentiation into a mineralizing phenotype and biomineralization. Only by integrating data from models on all levels (i.e. a single cell to the whole organism) can various critical aspects of periodontal wound healing/regeneration be fully evaluated.

Evaluation of a topical herbal patch for soft tissue wound healing: an animal study.

AIM: This study evaluated the effects of a topical herbal patch (PerioPatch®) for gingival wound healing in a rat model. MATERIALS AND METHODS: A mid-crestal incision was performed on each side of the edentulous anterior maxilla in 48, 6-month-old, Wistar rats. Full-thickness flaps were raised, repositioned and sutured. Four experimental groups were established: herbal patch, placebo patch, no patch and no patch and no surgery. Patches were placed immediately after surgery and replaced every 12 h for the following 3 days. Half of the animals were killed after 5 and the remaining ones after 12 days. Tissue blocks were retrieved and processed for histological and immunohistochemical evaluation. Epithelial gap, collagen contents, amount of macrophages, cellular proliferation and vascular contents were evaluated in the central incision area. Statistical analysis consisted of two-way anova. RESULTS: The herbal patch group presented the smallest epithelial gap at 12 days, the highest collagen content both at 5 and 12 days, a larger number of proliferating cells at day 5 and more numerous blood vessels at day 12. Macrophage number was similar in all groups. CONCLUSION: Herbal patch improved wound healing in this animal model.

Bone remodeling at implants with different configurations and placed immediately at different depth into extraction sockets. Experimental study in dogs.

OBJECTIVES: This study evaluated the effect of implant macrodesign and position, related to the bone crest, on bone-to-implant contact (BIC) and crestal bone (CB) in immediate implants. MATERIAL AND METHODS: The study comprised of six foxhound dogs in which 48 immediate implants were placed. Three types of implants from the same manufacturer with similar surface characteristics but different macrodesigns were randomly placed: Group A (external hex with no collar microthreads), Group B (internal hex and collar microrings), and Group C (internal conical connection and collar microrings). Half of the implants were placed leveled with the bone crest (control) and the remaining, 2 mm subcrestally (test). Block sections were obtained after 12 weeks and processed for mineralized ground sectioning. Statistical analysis consisted of nonparametric Friedman and Wilcoxon test. RESULTS: All implants were clinically stable and histologically osseointegrated. Mean BIC percentage within the control group was as follows: A: 42.52 ± 8.67, B: 35.19 ± 18.12, and C: 47.46 ± 11.50. Within the test group: A: 47.33 ± 5.23, B: 48.38 ± 11.63, and C: 54.88 ± 11.73. Differences between each subgroup in the test and the control groups were statistically significant. BIC was statistically significantly higher in the test (50.588 ± 8.663) than in the control (43.317 ± 9.851) group. Within both groups, differences between group C and the other 2 were statistically significant. Distance from the implant shoulder to the buccal CB was statistically significantly larger in the control than in the test group and between subgroups B and C in the control and test groups. Within the test groups, relative bone gain was noticed. CONCLUSIONS: Subcrestal immediate implant positioning may lead to a relatively reduced CB resorption and increased BIC. Implants macrodesign with crestal microrings may enhance BIC in post-extraction implants.

Timing of implant placement and augmentation with bone replacement material: clinical assessment at 8 and 16 months.

PURPOSE: The purpose of this study is to evaluate implants placed at different times of bone augmentation. MATERIALS AND METHODS: Four implants were placed in seven dogs: one at a 6-month bovine mineral grafted site (6-month Bio-Oss® grafted site [6mBio]), one at a grafted membrane-protected simultaneously augmented (Fresh Bio-Oss® grafted site [FrBio]) site, one at a clotted (nongrafted clotted membrane-protected site [Clot]) membrane-protected site, and one at a pristine (nongrafted uncovered site [Cont]) site. Implants were exposed after 6 months. The same protocol was repeated on the contralateral side, at a delay of 8 months. Peri-implant care was performed throughout the hygienic phase (2 and 10 months, respectively) every 48 to 72 hours. Probing depth and bleeding on probing were recorded. Implant stability was determined by a Periotest® (Medizintechnik Gulden, Modautal, Germany). Statistical analysis was conducted using analysis of variance with repeated measures. RESULTS: Average probing depth at the simultaneously grafted sites was 2.21 mm and 2.03 mm at 8 and 16 months, respectively. At the 6-month grafted sites, it was 1.96 mm and 1.57 mm. At the Clot sites, it was 2.68 mm and 2.07 mm, and 2.21 mm and 1.82 mm at the Cont sites, respectively. The average bleeding on probing was 0.50 and 0.42 at the FrBio sites, and 0.35 and 0.07 at the 6mBio sites during the respective periods. At the Clot sites, it was 0.50 and 0.28, and at the Cont sites, 0.43 and 0.21, respectively. Probing depth significantly reduced over the time at 6mBio, Clot, and Cont sites (p < .03). Average implant stability score at the FrBio sites was -0.24 and -0.27, and -0.50 and -0.46 at the 6mBio sites, at 8 and 16 months, respectively. At the Clot sites, it was -0.35 and -0.46. Cont sites averaged -0.37 at both periods. Implant stability was significantly higher (p < .005) comparing 6mBio over FrBio, 6mBio over Cont, and Clot over FrBio sites. CONCLUSIONS: Immediate and delayed augmentations are safe modes. Probing depth and bleeding indices gradually improved along time. Implant stability was higher at the delayed mode.

Clinical and histomorphometric observations around dual acid-etched and calcium phosphate nanometer deposited-surface implants.

PURPOSE: The objective of this study was to compare the clinical and histologic peri-implant parameters of a nano-calcium phosphate (CaP)-coated dual acid-etched (DAE) implant (n = 7) to those of an uncoated DAE implant (n = 7). MATERIALS AND METHODS: The study included seven dogs who received implants bilaterally in edentulous mandibular areas; in the right side, procedures were performed 8 months after procedures in the left mandible. Clinical parameters were measured prior to euthanasia (8 months after the second set of implants was placed), followed by histologic nondecalcified processing for morphometric evaluation. Bone-implant contact (BIC), crestal bone resorption (CBR), intrabony defect (IBD), and bone area fraction (BAF) were measured. Analysis of variance with repeated measures and a two-tailed Pearson correlation test were applied. RESULTS: Probing depth, Bleeding Index, and keratinized mucosal height were stable in both groups; there was a significant improvement in probing depths with time (P = .014). Morphometric measurements showed BIC from 75% to 89% in both groups at 8 and 16 months. The nano-CaP-coated group (n-CaP) showed a significant increase in BIC over time when compared to the DAE group (P = .02). Crestal bone level was maintained in both groups with average resorption of 1.4 to 1.5 mm at the n-CaP implants and 1.1 to 1.2 mm at the DAE implants at 8 and 16 months, respectively. Mean IBD values were 0.88 to 1.18 mm at the n-CaP implants and 0.65 to 0.66 mm at the DAE implants at the respective periods. CONCLUSIONS: Within the limitations of this study, both the DAE and the n-CaP-surface implants showed successful osseointegration and functional soft and hard tissue adaptation. Except for the significant increase in BIC around the n-CaP implants over time, both showed similar clinical and histologic findings.