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Objectives Periodontal disease and diabetes have an extensively investigated bidirectional correlation. Non-surgical periodontal treatment (NSPT) was proven to contribute to glycemic control. Moreover, it may benefit from the association of adjunctive therapies. The aim of the present systematic review is to assess the clinical efficacy of NSPT in association with laser (LT) or photodynamic therapy (PDT) in controlled or uncontrolled diabetic patients, and to grade the level of evidence. Materials and methods Randomized controlled clinical trials with at least 3-month follow-up were searched in MEDLINE via OVID, EMBASE, and Cochrane Central, screened for inclusion, and grouped based on the performed treatments, follow-up time, type of diabetes, and level of glycemic control. Results Eleven RCTs with 504 total subjects were included. The adjunct of PDT showed a statistically significant 6-month difference in PD changes (with low certainty of evidence), but not in CAL changes, while a significant difference in 3-month PD and CAL changes was found with the adjunct of LT (low certainty of evidence). Patients treated with PDT registered a higher decrease in HbA1c levels at 3 months, but no significant difference was noted at 6 months; LT also led to better HbA1c changes at 3 months with a moderate certainty of evidence. Conclusion Despite the promising short-term HbA1c decrease, the results should be interpreted with caution due to the small effect sizes and the statistical heterogeneity, and further evidence from well-designed RCTs is needed to support the routine use of PDT or LT in adjunct to NSPT.

Purpose: To present medium- and long-term biologic outcomes of implant-supported single-tooth restorations and fixed partial dentures and to analyze their correlations with prosthesis and patient characteristics. Materials and methods: The records of patients treated with implant-supported fixed restorations between 2004 and 2019 reporting the presence or absence of peri-implantitis and/or implant failure were analyzed. The cumulative survival rate (%) over time was calculated, as well as the cumulative prevalence of units free of peri-implantitis. Results: A total of 344 implants in 112 patients were included, with a mean follow-up period of 5.3 ± 4.0 years after loading. The cumulative survival rates for implants supporting single crowns and fixed partial dentures were 98.11% and 100% after 5 years, respectively, and 97.43% and 98.96% after 10 years, with an overall survival rate of 91.69% after 12 years. At the patient level, the implant survival rates were 95.42%, 92.73%, and 85.31% at 5, 10, and 12 years, respectively. The cumulative rate of implants free from peri-implantitis was 87.46% at the implant level and 72.39% at the patient level. Implant and prosthesis characteristics did not affect the long-term occurrence of implant failure or peri-implantitis. The development of peri-implantitis was statistically correlated with patient smoking habits, but not with history of periodontitis or with diabetes mellitus. Conclusion: Implants supporting single crowns and fixed partial dentures showed relatively high medium- and long-term survival rates that were not influenced by the implant or prosthesis characteristics, including the retention method. As for patient characteristics, only smoking was correlated with the occurrence of peri-implantitis.

Background Considering the role of the inflammatory host response in the pathogenesis of periodontitis, different host modulators have been proposed to enhance the outcomes of non-surgical periodontal therapy (NSPT), but their efficacy has not been fully clarified. Objectives This systematic review investigated the efficacy of host modulators combined with NSPT in reducing probing pocket depth (PPD) in periodontitis patients. Materials and methods Placebo-controlled RCTs with ≥6 months follow-up were searched. Meta-analysis was conducted when ≥5 studies using the same host modulator were identified. Results Fifty eight studies met the inclusion criteria. After 6 months, local administration of 1.2% statin gels as adjuncts to NSPT significantly improved PPD reduction (1.83 mm) in infrabony defects and systemic administration of sub-antimicrobial dose doxycycline (SDD) in addition to NSPT improved PPD reduction of deep pockets. Administration of probiotics conferred limited clinical benefits. Local bisphosphonate and metformin gels showed potential for clinical use in infrabony defects, which needs to be confirmed. Conclusions Local delivery of statins in infrabony defects and systemic SDD for deep pockets may confer additional clinical benefits to NSPT. Their long-term effectiveness and safety need to be confirmed in independent multi-centred studies. Further studies are needed to confirm the benefit of other host modulators.

This systematic review aims to assess the available literature on the clinical efficacy of hand versus power-driven instruments for subgingival instrumentation during surgical periodontal therapy (ST).A search of the literature was carried out on MEDLINE via Ovid, Embase, Web of Science, the Cochrane Database, LILACS, and Scopus. RCTs comparing the use of powered instruments (test) to hand scalers (control) for subgingival instrumentation in terms of changes in probing pocket depth (PPD) after surgical periodontal treatment were included and screened in duplicate. Descriptive synthesis of the data and risk of bias assessment were undertaken.Four RCTs met the inclusion criteria and were included in this systematic review. ST in all studies was performed by means of open flap debridement. Gracey curettes were the most commonly used hand instruments, while sonic and ultrasonic devices were used in the test group. Sites with initial PPD ≥ 6 mm had pocket reduction ranging from 2.93 to 4.89 mm in the control group and from 2.77 to 3.86 mm in the test group. All studies found no significant difference between the different types of instruments/devices in terms of PPD reduction.Despite the limited number of studies, both manual and power-driven instruments appear to be effective in reducing PPD after surgical treatment of periodontitis.Based on the findings of this systematic review, the clinician may make a decision whether to use manual or powered instruments during ST on a case-by-case basis and considering other factors, such as the risk of creating high concentrations of aerosols.

The fast degradation of collagen-based membranes in the biological environment remains a critical challenge, resulting in underperforming Guided Bone Regeneration (GBR) therapy leading to compromised clinical results. Photoactive atelocollagen (AC) systems functionalised with ethylenically unsaturated monomers, such as 4-vinylbenzyl chloride (4VBC), have been shown to generate mechanically competent materials for wound healing, inflammation control and drug delivery, whereby control of the molecular architecture of the AC network is key. Building on this platform, the sequential functionalisation with 4VBC and methacrylic anhydride (MA) was hypothesised to generate UV-cured AC hydrogels with reduced swelling ratio, increased proteolytic stability and barrier functionality for GBR therapy. The sequentially functionalised atelocollagen precursor (SAP) was characterised via TNBS and ninhydrin colourimetric assays, circular dichroism and UV-curing rheometry, which confirmed nearly complete consumption of collagen primary amino groups, preserved triple helices and fast (within 180 s) gelation kinetics, respectively. Hydrogel swelling ratio and compression modulus were adjusted depending on the aqueous environment used for UV-curing, whilst the sequential functionalisation of AC successfully generated hydrogels with superior proteolytic stability in vitro compared to both 4VBC functionalised control and the commercial dental membrane Bio-Gide. These in vitro results were confirmed in vivo via both subcutaneous implantation and a proof-of-concept study in a GBR calvarial model, indicating integrity of the hydrogel and barrier defect, as well as tissue formation following 1-month implantation in rats., 11 figures, 2 tables, accepted on Acta Biomaterialia

Aim This review critically appraises the available knowledge on the pre-clinical and clinical use of bioactive factors for bone regeneration in the cranial and maxillofacial area. Materials and methods The use of growth factors, amelogenins and autologous platelet concentrates (APCs) for bone regeneration was reviewed in a systematic manner. More specifically, pre-clinical and clinical studies on ridge preservation, alveolar ridge augmentation, regeneration of peri-implant defects and sinus augmentation models were considered. Results Amongst different bioactive factors, the highest pre-clinical and clinical evidence of a positive effect on bone formation is associated with rhBMP-2 and the lowest with amelogenins. While APCs seem to accelerate clinical healing and reduce postoperative discomfort, there is insufficient and contrasting evidence of a significant effect on hard tissue regeneration for the different clinical applications. Conclusions Although there is increasing evidence that bioactive factors might enhance the bone regeneration process, the great heterogeneity of the available studies and the limited number of RCTs do not allow to draw robust conclusions. Issues that still need to be investigated include the optimal carriers for bioactive agents (direct vs. indirect), the dosage, the timing of administration, as well as the possibility of combining different agents to promote synergistic effects.

Aims To compare tooth- (TSRP) and implant-supported (ISRP) removable prostheses in terms of abutment and prosthesis survival (PICO 1) and estimated cumulative survival of teeth/implants and prostheses (PICO 2) at ≥12-month post-prosthesis delivery in patients with stage IV periodontitis. Materials and methods Five databases were searched to identify RCTs, CCTs, single arms, prospective cohort studies, case series and retrospective studies. Duplicate screening was performed, and ranges for abutment and prosthesis survival were calculated. Results Twenty-six studies were included in the qualitative assessment. Only one study with critical risk of bias comparing the two treatment modalities reported similar survival rates at 2 years. Overall, prospective studies on ISRPs indicated an implant survival rate ranging from 96.4% to 100% and a prosthesis survival rate of 100% with a follow-up from 12 to 54 months. Prospective studies on TSRPs indicated a tooth survival ranging from 85.71% to 100% at 1- to 10-years follow-up. Conclusions The available evidence is of poor quality, and it does not allow to make robust conclusions on the efficacy of these rehabilitations in stage IV periodontitis patients. Particularly for TSRPs, careful patient selection is crucial and a certain number of biological and prosthetic complications should be expected.

Objectives To follow-up the radiographic bone level changes and the clinical outcomes of immediately provisionalized and conventionally restored implants with a hydrophilic surface following 5 years of function. Materials and methods This was a 5-year follow-up of a prospective, randomized, single-blind controlled study involving 16 of the 24 originally recruited patients in need of a single-tooth replacement in the esthetic area. Implants were either immediately provisionalized with a non-occluding temporary crown (test group, n = 7), or left without a crown (control group, n = 9). In both groups, the definitive restoration was placed 16 weeks after implant placement. Radiographic and clinical parameters were evaluated at 36, 48, and 60 months post-implant placement, together with implant survival and success rates. The esthetic outcomes were measured with the Papilla Fill Index (PFI) and the Pink Esthetic Score (PES). Results At 60 months, similar peri-implant bone loss was observed in the test (-0.42 mm ±0.17 mm) and in the control (-0.37 mm ±0.35 mm) groups. A tendency for an improved esthetic outcome from implant loading to the subsequent follow-ups was noticed in both groups. Both groups presented with high levels of long-term implant survival and success. Conclusions This study supports non-functional immediate provisionalization as a viable long-term option for the management of single-tooth implants in the esthetic area. However, the small sample size does not allow statistical inference at 60 months of follow-up and future adequately powered studies are warranted.

Background and Aims To review the regenerative technologies used in bone regeneration: bone grafts, barrier membranes, bioactive factors and cell therapies. Material and Methods Four background review publications served to elaborate this consensus report. Results and Conclusions Biomaterials used as bone grafts must meet specific requirements: biocompatibility, porosity, osteoconductivity, osteoinductivity, surface properties, biodegradability, mechanical properties, angiogenicity, handling and manufacturing processes. Currently used biomaterials have demonstrated advantages and limitations based on the fulfilment of these requirements. Similarly, membranes for guided bone regeneration (GBR ) must fulfil specific properties and potential biological mechanisms to improve their clinical applicability. Pre‐clinical and clinical studies have evaluated the added effect of bone morphogenetic proteins (mainly BMP ‐2) and autologous platelet concentrates (APC s) when used as bioactive agents to enhance bone regeneration. Three main approaches using cell therapies to enhance bone regeneration have been evaluated: (a) “minimally manipulated” whole tissue fractions; (b) ex vivo expanded “uncommitted” stem/progenitor cells; and (c) ex vivo expanded “committed” bone‐/periosteum‐derived cells. Based on the evidence from clinical trials, transplantation of cells, most commonly whole bone marrow aspirates (BMA ) or bone marrow aspirate concentrations (BMAC ), in combination with biomaterial scaffolds has demonstrated an additional effect in sinus augmentation and horizontal ridge augmentation, and comparable bone regeneration to autogenous bone in alveolar cleft repair.

Increased life expectancy and broader restorative dental treatment alternatives for missing teeth have resulted in an increasing request of bone regeneration/augmentation procedures not only in healthy patients, but also in elderly and medically compromised ones. This is also combined with a growing demand for short implant loading protocols and for optimal aesthetic results. In order to meet these new dental needs, personalized treatment strategies tailored on each individual's characteristics and healing profile are warranted. Omics technologies are emerging as powerful tools to uncover molecules and signalling pathways involved in bone formation and osseointegration and to investigate differences in the molecular mechanisms between health and systemic diseases that could be targeted by future therapies. This review critically appraises the available knowledge on the application of omics technologies in the field of bone regeneration and osseointegration and explores their potential use for personalized medicine in the dento-maxillo-facial field. Significance The use of omics in personalising dental maxillo-facial treatments emerges as a desirable diagnostic and treatment strategy. Omics represent, in fact, powerful tools not only to shade light on the cascade of events taking place during bone formation/osseointegration, but also to identify specific signalling pathways and molecules that can be targeted by future therapies with the aim to enhance clinical outcomes in patients with compromised healing conditions.

Although collagen membranes have been clinically applied for guided tissue/bone regeneration for more than 30 years, their in vivo degradation pattern has never been fully clarified. A better understanding of the different stages of in vivo degradation of collagen membranes is extremely important, considering that the biology of bone regeneration requires the presence of a stable and cell/tissue-occlusive barrier during the healing stages in order to ensure a predictable result. Therefore, the aim of this study was to investigate the degradation pattern of a porcine non-cross-linked collagen membrane in an in vivo model of guided bone regeneration (GBR).Decalcified and paraffin-embedded specimens from calvarial defects of 18, 10-month-old Wistar rats were used. The defects were treated with a double layer of collagen membrane and a deproteinized bovine bone mineral particulate graft. At 7, 14 and 30 days of healing, qualitative evaluation with scanning electron microscopy and atomic force microscopy, and histomorphometric measurements were performed. Markers of collagenase activity and bone formation were investigated using an immunofluorescence technique.A significant reduction of membrane thickness was observed from 7 to 30 days of healing, which was associated with progressive loss of collagen alignment, increased collagen remodeling and progressive invasion of woven bone inside the membranes. A limited inflammatory infiltrate was observed at all time points of healing.The collagen membrane investigated was biocompatible and able to promote bone regeneration. However, pronounced signs of degradation were observed starting from day 30. Since successful regeneration is obtained only when cell occlusion and space maintenance exist for the healing time needed by the bone progenitor cells to repopulate the defect, the suitability of collagen membranes in cases where long-lasting barriers are needed needs to be further reviewed.

Background Three millimeter is considered as the minimum distance to obtain soft and bone tissue stability in case of adjacent implants. The possibility to preserve peri-implant bone level using a platform switching connection has questioned this concept. Purpose The study evaluates soft tissue maintenance and marginal bone stability around implants, placed at 2 or 3 mm of distance. Materials and methods Thirty patients received two immediately loaded implants either at 2-mm (test) or at 3-mm (control) of distance in the premolar area. Soft tissue esthetics (papilla height and fill, keratinized tissue, recession) and radiographic peri-implant bone level changes were measured at 3, 6, and 12 months. Results No significant differences between the two groups were detected neither for all soft tissue esthetic outcomes nor for bone level modifications up to 12 months. Conclusion The results suggested that up to 12 months post-loading, both 2- and 3-mm inter-distance platform-switched implants in healed site, supported adequate esthetic outcomes and peri-implant bone stability.

Objective To compare a behavioural management program (test) to a standard communication approach (control) to reduce plaque, improve clinical outcomes and patient's compliance with oral self-care. Background Since psychological factors affect oral health-related behaviours, approaches directed at changing behaviours and improving compliance might improve the effect of oral health education. Materials and methods This was a randomized, single-blind, parallel-design trial involving 71 patients with mild to moderate periodontitis. During a run-in period, all participants began using a power toothbrush. Two sessions of non-surgical periodontal therapy were performed post-baseline, along with one of the two oral healthcare communication approaches. Plaque and bleeding scores, probing pocket depth (PPD) and clinical attachment level (CAL) were recorded at the screening visit, baseline visit and at 8 and 14 weeks post-baseline. Patients were asked to fill in oral self-care diaries. Experience questionnaires were administered to both clinicians and patients to assess subjective experience of the clinician-patient interactions during the visits. Results In both groups, a significant reduction in plaque and bleeding scores was observed from baseline to 8 weeks after baseline, which then remained stable at week 14, but no differences between the groups were noted. An improvement in CAL and PPD was recorded at week 8 post-baseline in the test compared to the control group. No inter-group differences in the clinician's and subject's experience questionnaires were observed. Conclusion Both approaches significantly promoted periodontal health. However, changing lifestyle requires repeated communication/engagement over time and a behavioural management program based upon two visits did not provide additional benefit compared to a standard approach.

Bone regeneration is a complex biological process, where the molecular mechanisms are only partially understood. In an ageing population, where the prevalence of chronic diseases with an impact on bone metabolism is increasing, it becomes crucial to identify new strategies that would improve regenerative outcomes also in medically compromised patients. In this context, omics are demonstrating a great potential, as they offer new insights on the molecular mechanisms regulating physiologic/pathologic bone healing and, at the same time, allow the identification of new diagnostic and therapeutic targets. This review provides an overview on the current evidence on the use of transcriptomic and proteomic approaches in bone regeneration research, particularly in relation to type 1 diabetes and osteoporosis, and discusses future scenarios and potential benefits and limitations on the integration of multi-omics. It is suggested that future research will leverage the synergy of omics with statistical modeling and bioinformatics to prompt the understanding of the biology underpinning bone formation in health and medically compromised conditions. With an eye toward personalized medicine, new strategies combining the mining of large datasets and bioinformatic data with a detailed characterization of relevant phenotypes will need to be pursued to further the understanding of disease mechanisms.

Objectives To histologically define the healing events occurring in calvarial critical size defects (CSDs) following treatment with a collagen barrier for guided bone regeneration (GBR) and a particulate graft in healthy and osteoporotic conditions. Material and Methods Thirty-six 10-month-old, female, Wistar rats were used in this study. Half of them were ovariectomized (OVX) and fed with a low-calcium diet to induce an osteoporotic-like status. In each animal of both groups, two 5-mm CSDs were created, one in the centre of each parietal bone, and they were treated with a deproteinized bovine bone mineral (DBBM) particulate graft and a bi-layer collagen membrane. Six OVX and six healthy control rats were randomly euthanized at 7, 14 and 30 days. One defect per animal was randomly processed for decalcified histology. Three central sections were used for qualitative histology and histomorphometric analysis. Results No significant difference in terms of percentage of newly formed bone was detected between the two groups at the different healing periods. However, a trend towards less bone formation and of poorer quality, expressed as reduced bone maturation, was detected in the OVX animals at 30 days. Discussion According to this study, GBR with a collagen barrier and a DBBM graft can be successfully obtained also in osteoporotic-like conditions. Future studies considering longer healing periods and controlling for the confounding factors arising from the use of a particulate graft are needed to confirm these data.

BACKGROUND The aim of the study was to evaluate the use of enamel matrix derivative (EMD) alone or in association with deproteinized bovine bone mineral (DBBM) for the treatment of partially contained intrabony defects. METHODS A total of 20 two-walled intrabony defects belonging to nine patients were included. Ten defects were treated with EMD alone (test group 1) and the other 10 were treated with EMD and DBBM (test group 2), applying either modified papilla preservation technique or simplified papilla preservation technique. RESULTS Twelve months after surgery, in the test group 1, PD was 2.8 ± 0.8 mm, REC was 2.3 ± 2.4 mm and CAL was 5.0 ± 2.8 mm, significantly reduced from baseline values (P < 0.05). Likewise, in test group 2, PD, REC and CAL reduced to 3.0 ± 0.7 mm, 3.9 ± 1.5 mm and 6.9 ± 1.1 mm respectively, from baseline values at 12 months (P < 0.05). No significant differences between groups were found. CONCLUSIONS The results showed that the use of EMD alone and the use of a combination of EMD and DBBM for the treatment of partially contained defects showed comparable clinical and radiographic outcomes after 12 months.

Objectives The aim of this systematic review was to assess whether the systemic skeletal reduction of bone mineral density (BMD) that characterizes osteoporotic subjects is also associated with a reduction of BMD in the jawbones. Material and methods Two reviewers searched independently and in duplicate three databases up to May 2014 and assessed the risk of bias using a tailored version of the Newcastle-Ottawa scale (NOS). Only papers reporting either Pearson's correlation coefficient or Spearman's rank correlation coefficient between skeletal and jawbone mineral density in more than five osteoporotic subjects were selected. Results From 1763 citations, 64 full-text papers were screened and five papers that met the inclusion criteria were included in the final analysis. None of the included studies complied with all NOS criteria, and as only two studies were eligible for meta-analysis, this was not performed. Conclusions Only limited conclusions can be drawn from this systematic review, due to the small number of studies included, their heterogeneity, and their high risk of bias. Future studies that take into consideration both upper and lower jaws, that use the same technique to measure skeletal and jaw BMD (ideally dual-energy X-ray absorptiometry, DXA), and that account for confounding variables (such as medications/diseases affecting bone metabolism and demographics) are needed to provide more robust conclusions.

Osteoporosis is one of the most common skeletal disorders affecting a significant percentage of people worldwide. Research data suggested that systemic diseases such as osteoporosis could act as risk factors for osseointegration, jeopardizing the healing process and thus the predictability of dental implant success on compromised patients. It is well accepted that preclinical studies in animal models reproducing the osteoporotic condition are one of the most important stages in the research of new biomaterials and therapeutic modalities. The aim of this systematic review was to investigate whether osteoporosis compromises dental implant osseointegration in experimental osteoporotic-like conditions. A 3-stage systematic literature research was conducted in MEDLINE via OVID and EMBASE up to and including March 2017. Experimental studies reporting on dental implant osseointegration on different osteoporotic animal models were assessed. The studies had to report on the percentage of bone-to-implant contact (%BIC) as the primary outcome. ARRIVE guidelines for reporting on animal research were applied to evaluate the methodological quality and risk of bias of the studies. Fifty-seven studies met the inclusion criteria and were assessed qualitatively. The most adopted animal model was the rat. A variability of %BIC values was observed, ranging from 30% to 99% and from 26% to 94% for the healthy and osteoporotic group, respectively. The great majority (47) of the included studies concluded that estrogen deficiency significantly affects BIC values, 9 studies stated that it was not possible to observe statistical differences in BIC between ovariectomized and healthy groups and 1 study did not provide a comparison between the healthy and osteoporotic group. Owing to the great heterogeneity in implant surface, study design, observation time-points, site of implant placement and reported outcomes, a meta-analysis could not be performed. An overall high risk of bias was observed, owing to the limited information on animal housing and husbandry, baseline characteristics and health status, ethical statement and allocation to the experimental groups provided. Although the available studies seem to suggest a lower osseointegration in osteoporotic-like conditions, no robust conclusions can be drawn due to the great heterogeneity and overall low quality of the available studies. Future studies with emphasis on minimizing the possible sources of bias and evaluating osseointegration of dental implants placed into jawbones instead of long bones are warranted.

Background and objectives There is significant evidence that, during the early stages of osseointegration, moderately rough hydrophilic (SLActive) surfaces can accelerate osteogenesis and increase bone-to-implant contact in comparison to hydrophobic (SLA) surfaces. However, very little is known regarding the molecular mechanisms behind the influence that surface chemistry modifications to increase hydrophilicity determine on bone healing. The aim of this study was to describe for the first time the proteins and related signalling pathways expressed during early osseous healing stages under SLA and SLActive titanium domes for guided bone regeneration. Material and methods One SLA and 1 SLActive dome with an internal diameter of 5.0 mm and a height of 3.0 mm were secured to the parietal bones of nine 6-month-old male New Zealand rabbits. Three animals were randomly euthanized at 4, 7 and 14 days and the newly formed tissues retrieved under the domes were analysed with liquid chromatography-mass spectrometry/mass spectrometry. STRING and KEGG databases were applied for Gene Ontology and pathway analyses. Results A different modulation of several pathways was detected between the 2 groups at all healing times. The main differences in the osseous healing response associated to the 2 surfaces were related to pathways involved in regulating the inflammatory response, differentiation of osteoblast precursors and skeletogenesis. At day 7, the highest number of proteins and the highest cellular activity were observed in both groups, although a more complex and articulated proteome in terms of cellular metabolism and signal transduction was observed in SLActive samples. Conclusion This is the first study describing the proteome expressed during early healing stages of guided bone regeneration and osseointegration. A combination of enhanced early osteogenic response and reduced inflammatory response were suggested for the hydrophilic group. Future studies are needed to corroborate these findings and explore the molecular effects of different titanium surfaces on the cascade of events taking place during bone formation.

Objectives To compare the radiographic bone changes, clinical parameters and aesthetic outcomes of immediately provisionalised and conventionally restored implants at 12- and 24-months post-implant placement. Material and methods In 24 patients, 24 bone level implants with a hydrophilic (SLActive) surface were placed in healed sites and they were either immediately provisionalised with a non-occluding temporary crown (test group) or left without a crown (control group). In both groups, the definitive restoration was placed 16 weeks after implant placement. Clinical and radiographic parameters were calculated at 12- and 24-months post-implant placement, together with implant success/survival rates according to three different sets of criteria. The aesthetic outcome was evaluated through the Papilla Fill Index and the Pink Aesthetic Score. Results The mean marginal bone loss at 1 year was −0.73 mm (SD 0.83 mm) in the test group and −0.22 mm (SD 0.46 mm) in the control group (p > .05). Whilst 100% survival rate and positive aesthetic outcomes were recorded in both groups, three patients of the test group did not fulfil all success criteria. Conclusions Immediate provisionalisation may represent a viable option for the replacement of single missing teeth, with radiographic, clinical and aesthetic results comparable to those of conventionally loaded implants at 2 years of follow-up.

Objectives To investigate the effect of experimental diabetes and metabolic control on intramembranous bone healing following guided bone regeneration (GBR). Material and methods Ninety-three Wistar rats were allocated to three experimental groups, healthy (H), uncontrolled diabetes (D) and controlled diabetes (CD). Twenty one days following diabetes induction, a standardised 5-mm defect was created at the mid-portion of each parietal bone. In 75 animals (25H, 25D, 25CD), one defect was treated with an intracranial and extracranial membrane according to the GBR principle, and one defect was left empty (control); five animals per group were then randomly sacrificed at 3, 7, 15, 30 and 60 days and processed for decalcified histology. In 18 animals (6H, 6D, 6CD), both defects were treated according to the GBR principle; three animals from each group were then randomly sacrificed at 7 and 15 days of healing and employed for gene expression analysis. Results Application of the GBR therapeutic principle led to significant bone regeneration even in the D group. However, at 15 and 30 days, the osteogenesis process was impaired by uncontrolled diabetes, as shown by the significant reduction in terms of defect closure (38–42%) and newly formed bone (54–61%) compared to the healthy group. The comparison of the D vs. H group at 15 days of healing yielded the largest number of genes with significantly differential expression, among which various genes associated with the ossification process (bmp4, ltbp4, thra and cd276) were identified. Conclusions Uncontrolled diabetes seems to affect early phases of the bone regeneration following GBR. A misregulation of genes and pathways related to cell division, energy production, inflammation and osteogenesis may account for the impaired regeneration process in D rats. Further studies are warranted to optimise the GBR process in this medically compromised patient population.

Different quantitative and qualitative indices calculated on oral panoramic radiographs have been proposed as useful tools to screen for reduced skeletal bone mineral density (BMD). Our aim was to systematically review the literature on linear and qualitative panoramic measures and to assess the accuracy of these indices by performing a meta-analysis of their sensitivity and specificity. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was followed. Fifty studies were included in the qualitative appraisal and 19 were considered for meta-analysis. The methodological quality of the retrieved studies, assessed with the QUADAS-2 tool, was on average low. Three indices were reported by most of the studies: mandibular cortical width, panoramic mandibular index, and the Klemetti index. Mandibular cortical width presented with a better accuracy in excluding osteopenia/osteoporosis (specificity), since patients with a cortical width more than 4 mm had a normal BMD in 90% of the cases. Almost all studies used a cutoff of 0.3 for the panoramic mandibular index, resulting in an estimated sensitivity and specificity in detecting reduced BMD, respectively, of 0.723 (SE 0.160; 95% confidence interval [CI], 0.352–0.926) and 0.733 (SE 0.066; 95% CI, 0.587–0.841). The presence of any kind of mandibular cortical erosion gave an estimated sensitivity and specificity in detecting reduced BMD, respectively, of 0.789 (SE 0.031; 95% CI, 0.721–0.843) and 0.562 (SE 0.047; 95% CI, 0.47–0.651) and a sensitivity and specificity in detecting osteoporosis, respectively, of 0.806 (SE 0.105; 95% CI, 0.528–0.9200) and 0.643 (SE 0.109; 95% CI, 0.417–0.820). The mandibular cortical width, panoramic mandibular index, and Klemetti index are overall useful tools that potentially could be used by dentists to screen for low BMD. Their limitations are mainly related to the experience/agreement between different operators and the different image quality and magnification of the panoramic radiographs.

Several systemic diseases (and relative medications) have been reported to impair or in some cases complicate dental implant surgery. In broader terms, when dealing with patients suffering from systemic diseases, the monitoring of the medical condition and of the related post-operative complications is of great importance in order to avoid risks which could jeopardise the health of the patient. In this review, the available evidence on implant survival/success, as well as relevant surgical recommendations in patients affected by systemic diseases, are evaluated and when possible, practical suggestions for the clinician are provided.

The aim of this review was to summarize the advantages and pitfalls of the available osteoporotic animal models of bone healing. A thorough literature search was performed in MEDLINE via OVID and EMBASE to identify animal studies investigating the effect of experimental osteoporosis on bone healing and bone regeneration. The osteotomy model in the proximal tibia is the most popular osseous defect model to study the bone healing process in osteoporotic-like conditions, although other well-characterized models, such as the post-extraction model, might be taken into consideration by future studies. The regenerative potential of osteoporotic bone and its response to biomaterials/regenerative techniques has not been clarified yet, and the critical size defect model might be an appropriate tool to serve this purpose. Since an ideal animal model for simulating osteoporosis does not exist, the type of bone remodeling, the animal lifespan, the age of peak bone mass, and the economic and ethical implications should be considered in our selection process. Furthermore, the influence of animal species, sex, age, and strain on the outcome measurement should be taken into account. In order to make future studies meaningful, standardized international guidelines for osteoporotic animal models of bone healing need to be set up.

Objectives To identify and describe protein expression in a Wistar rat calvarial critical size defect (CSD) model following treatment with guided bone regeneration in healthy and osteoporotic conditions. Material and methods Thirty-six 10-month-old female Wistar rats were used. Half of them were ovariectomized (OVX) and fed with a low-calcium diet to induce an osteoporotic-like status. In each animal of both groups, two 5-mm calvarial CSDs were treated with deproteinized bovine bone mineral graft particles and a bilayer collagen membrane. Six OVX and six control rats were randomly euthanized at 7, 14, and 30 days. One defect/animal was randomly chosen for proteomic analysis. Differently expressed proteins between the two groups were identified with matrix-assisted laser desorption time-of-flight mass spectrometry and liquid chromatography–mass spectrometry/mass spectrometry. Results At 7 days, 29 and 27 proteins were, respectively, identified in the healthy and OVX animals. At 14 days, 103 proteins were detected in the healthy controls and 20 proteins in the OVX rats, while at 30 days, 31 and 75 proteins were identified, respectively. Only limited proteins known to play a role in the later stages of bone formation and maturation were identified within the animals ‘proteomes. Discussion The osseous formation process was quite immature even at 30 days of healing. An overexpression of inflammatory and stress response pathways was detected in the OVX animals, as well as a tendency toward a delayed maturation of the osseous wound and a reduced/delayed differentiation of osteoblast cell precursors.

Objectives To investigate the gene expression and molecular pathways implicated in the regulation of the osseous healing process following guided bone regeneration (GBR). Material and methods Six 6-month-old Wistar male rats were used. Standardized 5-mm critical size defects were created in the parietal bones of each animal and treated with an extracranial and intracranial ePTFE membrane, according to the GBR principle. Three animals were randomly sacrificed after 7 and 15 days of healing. Total RNA was extracted from each sample and prepared for gene expression analysis. RNA quality and quantity were assessed, followed by hybridization of the cRNA to Affymetrix GeneChip Rat Genome 230 2.0 Arrays. The Affymetrix data were processed, and first-order analysis, quality control and statistical analysis were performed. Biological interpretation was performed via pathway and Gene Ontology (GO) analysis. Results Between the 7- and 15-day samples, 538 genes were differently regulated. At day 7, inflammatory and immune responses were clearly upregulated. In addition, GO terms related to angiogenesis and cell cycle regulation were overexpressed. At day 15, a more complex cellular activity and cell metabolism were evident. The bone formation processes were significantly overexpressed, with several genes encoding growth factors, enzyme activity, and extracellular matrix formation found as upregulated. Remarkably, a negative regulation of Wnt signalling pathway was observed at 15 days. Discussion The gene expression profile of the cells participating in osseous formation varied depending on the healing stage. A number of candidate genes that seem differentially expressed during early stages of intramembranous bone regeneration was suggested.

Background: Rough surface topography enhances the activation of Wnt canonical signaling, a pathway required for osteoblast differentiation. The present study investigated the effects of the modulation of prostaglandin E-2 (PGE(2)) signaling on osteoblastic differentiation on titanium surfaces for endosseous implants with different topographies. Methods: C2C12 cells were plated on polished or acid-etched/sand-blasted (SLA) titanium discs and stimulated with 1 mu M PGE(2) or 100 nM cyclooxygenase inhibitor indomethacin. Activation of Wnt canonical signaling was measured with a reporter system. Gene expression was measured in the same cell system by real-time polymerase chain reaction (RT-PCR). Osteoblastic MC3T3 cells were then plated on polished or SLA titanium discs with or without indomethacin, and their proliferation and the expression of osteoblast-specific genes was assessed by RT-PCR. Cell morphology was furthermore studied on SEM, and cell adhesion was assessed by fluorescent labeling of focal adhesion. Results: PGE(2) decreased Wnt signaling stimulation in cells growing on polished or SLA surfaces, while indomethacin increased the expression of Wnt target genes in C2C12 and MC3T3 cells, by reporter assay. Moreover, indomethacin increased the expression of early differentiation marker alkaline phosphatase in MC3T3 cells on polished discs and of late marker osteocalcin in cells on SLA titanium. Conclusions: Prostaglandin signaling affects the activation of Wnt canonical pathway in osteoblastic and mesenchymal cells on microstructured surfaces.

Statement of problem The position of dental implants placed with software-guided systems should be highly accurate in order to ensure safety and a passive fit of the immediate prosthesis. Purpose The purpose of this study was to measure the discrepancy between the clinical and software-planned position of dental implants by applying a photogrammetric method. Material and methods Two casts were obtained, 1 from the surgical template and 1 from the actual position of the implants on the alveolar ridge of a patient. Photogrammetry was then applied to precisely locate the position of each implant on the casts. Because this mathematical technique required the identification of image points and of the relative spatial coordinates, 4 marks were drilled on the implant screw. The position of the implants was then identified as the geometric center of the 4 marks, while the orientation of the implant axis was represented by a vector normal to the plane fitting the points. A series of 16 convergent images all around the object was made using a high-resolution digital camera. A mathematical method called “rototranslation” was used to superimpose the cast images for the comparison. Results The tests performed on the casts resulted in an average precision level of 4 μm for the locations and less than 1 degree for the axis of the implants. A series of empirical and numerical tests were performed to assess the performance of the procedure and of the measurement protocol. Conclusions The photogrammetric method is reproducible and can be used to measure the discrepancy between the software-planned and the real position of dental implants. Considering that the average precision level required for an implant-based prosthesis is approximately 50 μm, the error associated with this method can be considered as negligible.