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Suelen Cristina Sartoretto,1– 4 Jose Calasans-Maia,5 Rodrigo Resende,2,4,6 Eduardo Câmara,3 Bruna Ghiraldini,7 Fabio Jose Barbosa Bezerra,8 Jose Mauro Granjeiro,4,9 Monica Diuana Calasans-Maia4,6 1Oral Surgery Department, Universidade Veiga de Almeida, Rio de Janeiro, RJ, Brazil; 2Oral Surgery Department, Universidade Iguaçu, Nova Iguaçu, RJ, Brazil; 3Post-Graduation Program in Dentistry, Universidade Veiga de Almeida, Rio de Janeiro, RJ, Brazil; 4Clinical Research Laboratory, Dentistry School, Universidade Federal Fluminense, Niteroi, RJ, Brazil; 5Orthodontics Department, Dentistry School, Universidade Federal Fluminense, Niteroi, RJ, Brazil; 6Oral Surgery Department, Universidade Federal Fluminense, Niteroi, RJ, Brazil; 7Dental Research Division, Dentistry School, Universidade Paulista, São Paulo, SP, Brazil; 8Laboratory of Bioassays and Cell Dynamics, IBB-UNESP, Botucatu, Brazil; 9National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ, BrazilCorrespondence: Monica Diuana Calasans-Maia; Jose Mauro GranjeiroUniversidade Federal Fluminense, Rua Mario Santos Braga, 28/4 Floor, Niteroi, RJ, BrazilTel +55 21 98153-5884Email monicacalasansmaia@gmail.com; jmgranjeiro@gmail.comBackground and Objective: The success rates of dental implants in low-density bone have been reported as a challenge, especially for early or immediate loading in the maxilla posterior area. Nanoscale architecture affects the roughness, surface area, surface energy of the implant and can enhance osseointegration. This study aimed to evaluate the implant-surface topography and biomechanical, histomorphometric, and histological bone responses to a new nanostructured hydroxyapatite surface placed in the iliac crest of sheep.Methods: Ten female sheep (2– 4 years) received 30 implants (n=10/group): HAnano® coated (Epikut Plus®, S.I.N. Implant System, Sao Paulo, SP, Brazil), SLActive (BLX®, Straumann, Basel, Switzerland), and TiUnite (NobelActive®, Nobel Biocare, Göteborg, Sweden) surfaces. Scanning electron microscopy with energy-dispersive spectroscopy evaluated the implant surface topography, the insertion torque value, and resonance frequency analysis evaluated the primary stability, bone-implant contact, and bone-area fraction occupancy were evaluated after 14 and 28 days after implant placement.Results: The surface morphology was considerably comparable between the implant groups’; however, the TiUnite® group presented a remarkable different surface. The SLActive® and TiUnite® groups presented an insertion torque average of 74 (± 8.9) N/cm that was similar to that of HAnano® 72 (± 8.3) N/cm (p > 0.05). The resonance frequency evaluated with Osstell®/SmartPeg® or Penguin®/MulTipeg® showed similar results when assessing implants from the same group. BIC and BAFO significantly increased (p< 0.05) throughout the experimental periods to all groups, but BIC and BAFO values were similar among the implants at the same time point. After 4 weeks, bone-implant contact was higher than 80% of the total length analyzed. New bone occupies around 60% of analyzed area around the implants.Conclusion: HAnano® coated surface promoted comparable osseointegration as SLActive and TiUnite in the sheep model. The three tested surfaces showed comparable osseointegration at the early stages of low-density bone repair in the sheep model.Keywords: osseointegration, dental implant surface, nanotechnology, hydroxyapatite, sheep, bone response

Mônica Diuana Calasans-Maia,1 Carlos Alberto Brazil Barboza Junior,2 Carlos Alberto Soriano-Souza,3 Adriana Terezinha Neves Novellino Alves,4 Marcelo Jose de Pinheiro Uzeda,1 Victor R Martinez-Zelaya,3 Elena Mavropoulos,3 Maria Helena Rocha Leão,5 Ronaldo Barcellos de Santana,2 Jose Mauro Granjeiro,1 Alexandre Malta Rossi31Clinical Research in Dentistry Laboratory, School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 2Department of Periodontology, School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 3Department of Condensed Matter, Applied Physics and Nanoscience, Brazilian Center for Research in Physics, Rio de Janeiro, Brazil; 4Department of Stomatology. School of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil; 5Department of Biochemical Engineering, School of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilBackground and objective: Tetracycline and its derivatives, combined with calcium phosphates, have been proposed as a delivery system to control inflammatory processes and chronic infections. The objective of this study was to evaluate the microspheres of alginate encapsulated minocycline-loaded nanocrystalline carbonated hydroxyapatite (CHAMINO) as a biomimetic device to carry out target-controlled drug delivery for alveolar bone repair.Methods: CHAMINO microspheres were implanted in a rat central incisor socket after 7 and 42 days. New bone was formed in both groups between 7 and 42 days of implantation. However, the bone growth was significantly higher for the CHAMINO microspheres.Results: The minocycline (MINO) loading capacity of the nanocrystaline carbonated hydroxyapatite (CHA) nanoparticles was 25.1±2.2 μg MINO/mg CHA for adsorption over 24 hrs. The alginate microspheres containing minocycline-loaded CHA were biologically active and inhibited the Enterococcus faecalis culture growth for up to seven days of the MINO release. An osteoblastic cell viability assay based on the resazurin reduction was conducted after the cells were exposed to the CHAMINO powder and CHAMINO microspheres. Thus, it was found that the alginate extracts encapsulated the minocycline-loaded CHA microspheres and did not affect the osteoblastic cell viability, while the minocycline-doped CHA powder reduced the cell viability by 90%.Conclusion: This study concluded that the alginate microspheres encapsulating the minocycline-loaded nanocrystalline carbonated hydroxyapatite exhibited combined antibacterial activity against Enterococcus faecalis with cytocompatibility and osteoconduction properties. The significant improvement in the new bone formation after 42 days of implantation suggests that the CHAMINO microsphere has potential in clinical applications of bone regeneration.Keywords: nanomaterials, carbonated hydroxyapatite, minocycline, biocompatibility, bone regeneration

Victor R Martinez-Zelaya,1 Laila Zarranz,2 Edher Z Herrera,1 Adriana T Alves,2 Marcelo José Uzeda,2 Elena Mavropoulos,1 André L Rossi,1 Alexandre Mello,1 José M Granjeiro,2,3 Monica D Calasans-Maia,2 Alexandre M Rossi11Department of Condensed Matter, Applied Physics and Nanoscience, Brazilian Center for Research in Physics, Rio de Janeiro, RJ, Brazil; 2Dental Clinical Research Center, Oral Diagnosis Department and Oral Surgery Department, Dentistry School, Fluminense Federal University, Niteroi, RJ, Brazil; 3National Institute of Metrology, Quality and Technology, Duque de Caxias, RJ, BrazilBackground: Zinc-doped hydroxyapatite has been proposed as a graft biomaterial for bone regeneration. However, the effect of zinc on osteoconductivity is still controversial, since the release and resorption of calcium, phosphorus, and zinc in graft-implanted defects have rarely been studied.Methods: Microspheres containing alginate and either non-doped carbonated hydroxyapatite (cHA) or nanocrystalline 3.2 wt% zinc-doped cHA (Zn-cHA) were implanted in critical-sized calvarial defects in Wistar rats for 1, 3, and 6 months. Histological and histomorphometric analyses were performed to evaluate the volume density of newly formed bone, residual biomaterial, and connective tissue formation. Biomaterial degradation was characterized by transmission electron microscopy (TEM) and synchrotron radiation-based X-ray microfluorescence (SR-μXRF), which enabled the elemental mapping of calcium, phosphorus, and zinc on the microsphere-implanted defects at 6 months post-implantation.Results: The bone repair was limited to regions close to the preexistent bone, whereas connective tissue occupied the major part of the defect. Moreover, no significant difference in the amount of new bone formed was found between the two microsphere groups. TEM analysis revealed the degradation of the outer microsphere surface with detachment of the nanoparticle aggregates. According to SR-μXRF, both types of microspheres released high amounts of calcium, phosphorus, and zinc, distributed throughout the defective region. The cHA microsphere surface strongly adsorbed the zinc from organic constituents of the biological fluid, and phosphorus was resorbed more quickly than calcium. In the Zn-cHA group, zinc and calcium had similar release profiles, indicating a stoichiometric dissolution of these elements and non-preferential zinc resorption.Conclusions: The nanometric size of cHA and Zn-cHA was a decisive factor in accelerating the in vivo availability of calcium and zinc. The high calcium and zinc accumulation in the defect, which was not cleared by the biological medium, played a critical role in inhibiting osteoconduction and thus impairing bone repair.Keywords: zinc-doped carbonated hydroxyapatite, nanocomposite, synchrotron radiation-based X-ray microfluorescence, zinc/calcium bioavailability, bone regeneration

Objective: To evaluate the long-term survival and success rates of implants placed in reconstructed areas using microvascularized or non-microvascularized extraoral bone grafts., Materials and Methods: An electronic search was performed in five databases and in gray literature for articles published until June, 2023. The eligibility criteria comprised observational studies (prospective or retrospective) and clinical trials, reporting survival and success rates of implants placed in extraoral bone grafts. A meta-analysis (implant failure) was categorized into subgroups based on the type of bone graft used. The risk of bias within studies was assessed using the Newcastle-Ottawa Scale., Results: Thirty-one studies met the inclusion criteria. The mean follow-up time was 92 months. The summary estimate of survival rate at the implant level were 94.9% (CI: 90.1%-97.4%) for non-vascularized iliac graft, 96.5% (CI: 91.4%-98.6%) for non-vascularized calvaria graft, and 92.3% (CI: 89.1%-94.6%) for vascularized fibula graft. The mean success rate and marginal bone loss (MBL) were 83.2%; 2.25 mm, 92.2%; 0.93 mm, and 87.6%; 1.49 mm, respectively., Conclusions: Implants placed in areas reconstructed using extraoral autogenous bone graft have high long-term survival rates and low long-term MBLs. The data did not demonstrate clinically relevant differences in the survival, success, or MBL of grafts from different donor areas or with different vascularization. This systematic review was registered in INPLASY under number INPLASY202390004., (© 2024 Wiley Periodicals LLC.)

Purpose: To compare the fracture load of two framework materials, zirconia and a new fiber-reinforced composite (FRC), for full-arch implant-supported rehabilitations using various cross- sections., Material and Methods: A cobalt-chromium metal model simulating the all-on-four concept and including 2 anterior straight and 2 posterior 45- degree angled multi-unit digital implant analogs was manufactured. 4 straight multi-unit abutments were screwed onto the implant analogs. The metallic model was scanned, and 18 frameworks were fabricated, consisting of 9 made of zirconia and 9 made of fiber-reinforced composite (FRC). The frameworks were then divided into 6 groups, with each group consisting of 3 frameworks (n=3). Group division was based on material type (Zirconia or FRC Trilor) and framework cross-section: 3.5 x 6 mm2, 5.5 x 6 mm2, or 7.5 x 6 mm2. All specimens underwent thermocycling in 2 baths (5 ͦ c- 55 ͦ c for 2350 cycles). Subsequently, the frameworks were cemented to the abutments of the metal model and subjected to a load-to-failure bending test at 3 different points using a universal testing machine (crosshead speed: 1 mm/min) until complete fracture occurred (according to ISO/TS 11405:2015). Descriptive statistics were used to present quantitative variables as means ± standard deviations. To compare two means, Student's t-test or Mann-Whitney test was utilized, and for three means, ANOVA test was used., Results: The FRC group with a 7.5 x 6 mm2 cross-section exhibited the highest load-to-failure values (ranging from 1020 N to 2994N) , while the zirconia group with a 3.5 x 6 mm2 cross-section recorded the lowest values (ranging from 212 N to 1287 N). The material type and framework cross-section significantly affected the mean load-to-fracture values (p< 0.05). Regardless of the framework cross-section, the FRC group exhibited higher fracture loads than the zirconia group. In both materials, fracture load values were increased with larger framework cross-sectional areas, with the highest values observed at the inter-implant midpoint., Conclusion: The FRC Trilor demonstrated a fracture load that make it a suitable alternative to zirconia for all-on-four implant prosthetic frameworks.

This systematic review (SR) aimed to evaluate the antimicrobial potential of different types of platelet-rich fibrin (PRF) often used in regenerative treatments. An electronic search was performed in four databases and in Gray literature for articles published until January, 2023. The eligibility criteria comprised in vitro studies that evaluated the antimicrobial effect of different types of PRF. For the analysis of the risk of bias within studies, the modified OHAT (Office of Health Assessment and Translation) tool was used. For the evaluation of the results, a qualitative critical analysis was carried out in the synthesis of the results of the primary studies. Sixteen studies published between 2013 and 2021 were included in this SR. The antimicrobial effects of PRF variations (PRF, injectable PRF [I-PRF], PRF with silver nanoparticles [agNP-PRF], and horizontal PRF [H-PRF]), were analyzed against 16 types of bacteria from the oral, periodontal, and endodontic environments. All types of PRF showed significant antimicrobial action, with the antibacterial efficacy being more expressive than the fungal one. The I-PRF, H-PRF, and agNP-PRF subtypes improve antimicrobial activity. According to the OHAT analysis, no study was classified as having a high risk of bias. Evidence suggests that PRF variations have significant antimicrobial activity, with bacterial action being greater than fungal. Evolutions such as I-PRF, H-PRF, and agNP-PRF improve antimicrobial activity. Future studies analyzing the clinical effect of these platelets are fundamental. This SR was registered in INPLASY under number INPLASY202340016., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Bone critical-size defects and non-union fractures have no intrinsic capacity for self-healing. In this context, the emergence of bone engineering has allowed the development of functional alternatives. The aim of this study was to evaluate the capacity of ASC spheroids in bone regeneration using a synergic strategy with 3D-printed scaffolds made from poly (lactic acid) (PLA) and nanostructured hydroxyapatite doped with carbonate ions (CHA) in a rat model of cranial critical-size defect. In summary, a set of results suggests that ASC spheroidal constructs promoted bone regeneration. In vitro results showed that ASC spheroids were able to spread and interact with the 3D-printed scaffold, synthesizing crucial growth factors and cytokines for bone regeneration, such as VEGF. Histological results after 3 and 6 months of implantation showed the formation of new bone tissue in the PLA/CHA scaffolds that were seeded with ASC spheroids. In conclusion, the presence of ASC spheroids in the PLA/CHA 3D-printed scaffolds seems to successfully promote bone formation, which can be crucial for a significant clinical improvement in critical bone defect regeneration.

This study aimed to analyze the physicochemical and histological properties of nanostructured hydroxyapatite and alginate composites produced at different temperatures with and without sintering and implanted in rabbit tibiae. Hydroxyapatite-alginate (HA) microspheres (425-600 µm) produced at 90 and 5 °C without (HA90 and HA5) or with sintering at 1000 °C (HA90S and HA5S) were characterized and applied to evaluate the in vitro degradation; also were implanted in bone defects on rabbit's tibiae ( n = 12). The animals were randomly divided into five groups (blood clot, HA90S, HA5S, HA90, and HA5) and euthanized after 7 and 28 d. X-ray diffraction and Fourier-transform infrared analysis of the non-sintered biomaterials showed a lower crystallinity than sintered materials, being more degradable in vitro and in vivo . However, the sinterization of HA5 led to the apatite phase's decomposition into tricalcium phosphate. Histomorphometric analysis showed the highest ( p < 0.01) bone density in the blood clot group, similar bone levels among HA90S, HA90, and HA5, and significantly less bone in the HA5S. HA90 and HA5 groups presented higher degradation and homogeneous distribution of the new bone formation onto the surface of biomaterial fragments, compared to HA90S, presenting bone only around intact microspheres ( p < 0.01). The elemental distribution (scanning electron microscope and energy dispersive spectroscopy and μ XRF-SR analysis) of Ca, P, and Zn in the newly formed bone is similar to the cortical bone, indicating bone maturity at 28 d. The synthesized biomaterials are biocompatible and osteoconductive. The heat treatment directly influenced the material's behavior, where non-sintered HA90 and HA5 showed higher degradation, allowing a better distribution of the new bone onto the surface of the biomaterial fragments compared to HA90S presenting the same level of new bone, but only on the surface of the intact microspheres, potentially reducing the bone-biomaterial interface., (Creative Commons Attribution license.)

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 ( t -test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates.

Background and objectives : Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods : A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results : The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

The aim of this study was to assess the reporting quality of abstracts in systematic reviews (SRs) related to implant dentistry and to assess the possible factors associated with the reporting quality. Abstracts of SRs in the field of implant dentistry, published in the last 5 years, were searched. The reporting quality was assessed and scored using the PRISMA for Abstracts checklist (PRISMA-A). The overall PRISMA-A score (OPS) and relative score (OPS%) per review were calculated according to adherence to the criteria presented in the checklist. Multivariable linear regression was performed to identify possible factors associated with reporting quality. Overall, 310 SRs were eligible for this study. Based on the maximum PRISMA-A score (score of 12), the mean OPS was 6.5 and OPS% was 54.2%. The items 'title', 'objectives', and 'number of included studies' were those most frequently reported in the abstracts, while the items 'registration' and 'funding' were the least reported. According to multivariable linear regression, the geographical origin of the articles was the only factor associated with better quality of abstract reporting, with higher OPS for SRs from Europe when compared to North America (coefficient 0.73; P = 0.049). The reporting quality of abstracts in SRs related to implant dentistry is suboptimal and needs to be improved. Journals should encourage adherence to reporting checklists in SRs., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: This in vivo study, aimed to biomechanically, histomorphometrically and histologically evaluate an implant surface coated with nanostructured hydroxyapatite using the wet chemical process (biomimetic deposition of calcium phosphate coating) when compared to a dual acid-etching surface., Material and Methods: Ten sheep (2-4 years old) received 20 implants, 10 with nanostructured hydroxyapatite coating (HAnano), and 10 with dual acid-etching surface (DAA). The surfaces were characterized with scanning electron microscopy and energy dispersive spectroscopy; insertion torque values and resonance frequency analysis were measured to evaluate the primary stability of the implants. Bone-implant contact (BIC) and bone area fraction occupancy (BAFo) were evaluated 14 and 28 days after implant installation., Results: The HAnano and DAA groups showed no significant difference in insertion torque and resonance frequency analysis. The BIC and BAFo values increased significantly (p<0.05) over the experimental periods in both groups. This event was also observed in BIC value of HAnano group. The HAnano surface showed superior results compared to DAA after 28 days (BAFo, p = 0.007; BIC, p = 0.01)., Conclusion: The results suggest that the HAnano surface favors bone formation when compared to the DAA surface after 28 days in low-density bone in sheep., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Almeida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Zygomatic implants (ZI) have been frequently indicated to rehabilitate patients with extensive atrophies in alternatives to major bone reconstructions. It can be installed inside the maxillary sinus, called instrasinus zygomatic implant (IZI) or outside the maxillary sinus (EZI), depending on the surgery technique., Objective: To evaluate the survival and complication rates of ZI in longitudinal studies when compared with conventional implants (CI)., Methods: An electronic search was performed in five databases and in Gray literature for articles published until April, 2022. The eligibility criteria comprised observational cohort studies (prospective or retrospective) and randomized clinical trials (RCTs) with at least 5 years of follow-up, reporting survival rate of ZI versus CI. A meta-analysis was conduct with 18 studies., Results: A total of 5434 implants (2972 ZI and 2462 CI) were analyzed in 1709 patients. The mean survival rate was 96.5% ± 5.02 and 95.8% ± 6.36 for ZI and CI, respectively (mean follow-up time of 78 months). There were observed no statistically significant between ZI and CI in prospective studies (risk ratio [RR] of 1.21; 95% confidence intervals [CIs]: 0.28 to 5.28; chi-squared [Chi 2 ] = 11.37; I 2  = 56%; degrees of freedom [df] = 5; z-score = 0.25; P = 0.80), retrospective studies IZI (RR of 1.29; 95% CIs: 0.52 to 3.23; Chi 2  = 4.07; I 2  = 2%; df = 4; z-score = 0.55; P = 0.58) and retrospective studies EZI (RR of 0.72; 95% CIs: 0.31 to 1.66; Chi 2  = 1.99; I 2  = 0%; df = 3; z-score = 0.78; P = 0.44). The biological complications most related to ZI was sinusitis, followed by infection and oroantral communication., Conclusion: ZI have a high long-term survival rate (96.5% with a mean of 91.5 months of follow-up), showing no significant difference when compared with CI. The most prevalent biological complication is sinusitis, being most commonly to the IZI technique. This systematic review (SR) was registered in INPLASY under number INPLASY202280025., (© 2022 Wiley Periodicals LLC.)

Medication-related osteonecrosis of the jaw (MRONJ) is considered as a severe adverse side effect of specific drugs such as anti-resorptive and anti-angiogenic medications. Evidence suggests that MRONJ is linked to invasive dental procedures, mainly dentoalveolar surgery. Several preventive strategies to minimize the risk of developing MRONJ have been investigated. However, no investigation has been attempted to evaluate the therapeutic effect of local drug-delivery technology as a preventive strategy protocol. The aim of this study is to evaluate the efficacy of hydroxyapatite-containing doxycycline (HADOX) in rats with high-risk MRONJ development. All the rats used in this study were divided into seven groups. Six groups of rats out of seven were exposed to two different doses of antiresorptive drug therapy for four weeks before undergoing an upper incisor extraction. After 28 days, all the animals were euthanized, and the bone blocks were processed for histological and histomorphometrical evaluation. The histomorphometric analysis confirmed that newly formed bone (NFB) was present in all groups, with significant differences. NFB in the HADOX group treated with zoledronic acid at 4% showed (28.38; C.I. 22.29-34.48), which represents a significant increase compared to HA (15.69; C.I. 4.89-26.48) ( p = 0.02). A similar pattern was observed in the HADOX group treated with zoledronic acid 8% ZA treatment ( p = 0.001). Conclusions : HADOX did not inhibit any bone repair and reduced early inflammatory response. Hence, HADOX could promote bone healing in patients undergoing antiresorptive drug therapy.

Background and objectives : Calcium phosphates have been widely used as bone substitutes, but their properties are limited to osteoconduction. The association of calcium phosphates with osteoinductive bioactive molecules has been used as a strategy in regenerative medicine. Melatonin has been studied due to its cell protection and antioxidant functions, reducing osteoclastic activity and stimulating newly formed bone. This study aimed to evaluate the effect of topical application of melatonin associated with nanostructured carbonated hydroxyapatite microspheres in the alveolar bone repair of Wistar rats through histological and histomorphometric analysis. Materials and Methods: Thirty female Wistar rats (300 g) were used, divided randomly into three experimental groups ( n = 10), G1: nanostructured carbonated hydroxyapatite microspheres associated with melatonin gel (CHA-M); G2: nanostructured carbonated hydroxyapatite (CHA); G3: blood clot (without alveolar filling). The animals were euthanized after 7 and 42 days of the postoperative period and processed for histological and histomorphometric evaluation. Kruskal-Wallis and Dunn's post-test were applied to investigate statistical differences between the groups at the same time point for new bone and connective tissue variables. Mann-Whitney was used to assess statistical differences between different time points and in the biomaterial variable. Results: Results showed a greater volume of residual biomaterial in the CHA-M than the CHA group ( p = 0.007), and there were no significant differences in terms of newly formed bone and connective tissue between CHA and CHA-M after 42 days. Conclusions: This study concluded that both biomaterials improved alveolar bone repair from 7 to 42 days after surgery, and the association of CHA with melatonin gel reduced the biomaterial's biodegradation at the implanted site but did not improve the alveolar bone repair.

Objectives: The objectives of the study were to investigate the long-term prevalence of taste disorder (TD) and olfactory disorder (OD) and associated risk factors in the non-hospitalized southeastern Brazil population of COVID-19 patients., Methods: This cross-sectional open survey evaluated possible long-term OD and TD in non-hospitalized patients who had been diagnosed with COVID-19 for more than 30 days, through an online self-report questionnaire. Demographic data, comorbidities, symptoms, and the intensity of OD and TD at the time of diagnosis and at the time of completing the questionnaire were evaluated., Results: Three hundred five responses were included. The reported prevalence of OD and TD was 72.9% and 67.4%, respectively, in the moment of diagnosis; after a mean follow-up period of 179 days, 45% and 50% still had some degree of the symptoms. There was a positive correlation between age and the high prevalence of OD (p = 0.02). However, there was no correlation between age and TD (p = 0.961) and weight in relation to OD/TD (p = 0.500 and p = 0.636, respectively)., Conclusion: This study observed a high long-term prevalence of OD and TD associated with COVID-19, with a low recovery rate during the study period. There was a positive association between older participants and the prevalence of OD., (© 2022 Wiley Periodicals LLC.)

Peri-implantitis is characterized by nonreversible and progressive loss of supporting bone and is associated with bleeding and/or suppuration on probing. Peri-implant disease is considered as the main etiologic factor related to implant failure. Peri-implant disease has a pathogenesis similar to that of periodontal disease, both being triggered by an inflammatory response to the biofilm accumulation. Although the prevalence of peri-implantitis has been evaluated by several clinical studies with different follow-ups, there are currently little data on the impact of implant location and the prevalence of peri-implantitis. The aim of this review, therefore, was to summarize the evidence concerning the prevalence of peri-implantitis in relation to implant location and associated risk predictors. Even though most studies evaluating the prevalence of peri-implantitis in relation to implant location are cross-sectional or retrospective, they suggest that the occurrence of peri-implantitis is most prevalent in the anterior regions of the maxilla and mandible. Moreover, it seems that there is a higher prevalence of peri-implantitis in the maxilla than in the mandible., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Bioceramic nanometer coatings have been regarded as potential substitutes for plasma-sprayed hydroxyapatite coatings, and the association with bone morphogenetic protein (BMP) is an attempt to achieve faster osseointegration to hasten oral rehabilitation. Objective: This study aimed to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) on the osseointegration of titanium implants coated with a thin film surface of hydroxyapatite (HA). Methods: Two implants (n = 24) were placed in each white New Zealand rabbits’ femur (n = 6). Implants were placed in the right femur after standard instrumentation (A and B) and in the left femur after an over-instrumentation (C and D), preventing bone-implant contact. The distal implants were installed associated with rhBMP-7 (groups B [regular instrumentation] and D [over-instrumentation]) and, also, in the absence of without BMP (control groups A [regular instrumentation] and C [over-instrumentation]). After 4 weeks, the animals were euthanized. The bone blocks containing the implants were embedded in methyl methacrylate and sectioned parallel to the long axis of the implant, which were analyzed by image segmentation. The data were analyzed using a nonparametric statistical method. Results: We observed that Group A had a mean bone formation of 35.6% compared to Group B, which had 48.6% (p > 0.05). Moreover, this group showed 28.3% of connective tissue compared to Group A, with 39.3%. In the over-instrumented groups, rhBMP-7 (Group D) showed an enhanced and significant increase in bone formation when compared with the group without rhBMP-7 (Group C). Conclusion: We concluded that the association of rhBMP-7 to thin nanostructure HA-coated implants promoted greater new bone area than the same implants in the absence of rhBMP-7, mainly in cases of over-instrumented implant sites.

Background: The degree of biodegradation and the inflammatory response of membranes employed for guided bone regeneration directly impact the outcome of this technique. This study aimed to evaluate four different experimental versions of Poly (L-lactate-co-Trimethylene Carbonate) (PTMC) + Poly (L-lactate-co-glycolate) (PLGA) membranes, implanted in mouse subcutaneous tissue, compared to a commercially available membrane and a Sham group., Methods: Sixty Balb-C mice were randomly divided into six experimental groups and subdivided into 1, 3, 6 and 12 weeks (n = 5 groups/period). The membranes (1 cm 2 ) were implanted in the subcutaneous back tissue of the animals. The samples were obtained for descriptive and semiquantitative histological evaluation (ISO 10993-6)., Results: G1 and G4 allowed tissue adhesion and the permeation of inflammatory cells over time and showed greater phagocytic activity and permeability. G2 and G3 detached from the tissue in one and three weeks; however, in the more extended periods, they presented a rectilinear and homogeneous aspect and were not absorbed. G2 had a major inflammatory reaction. G5 was almost completely absorbed after 12 weeks., Conclusions: The membranes are considered biocompatible. G5 showed a higher degree of biosorption, followed by G1 and G4. G2 and G3 are considered non-absorbable in the studied periods.

Evidence shows that an increased width and thickness of the keratinized mucosa favours peri-implant health. The aim of this network meta-analysis was to compare the clinical effects of alternative biomaterials for peri-implant soft tissue phenotype modification (PSPM) in patients with dental implants when compared to autologous tissue grafts. An electronic search without language or date limitations was performed in four databases and the grey literature for articles published until November 2020. The eligibility criteria included randomized clinical trials (RCTs) evaluating the clinical outcomes of biomaterials for PSPM. A pairwise and network meta-analysis was conducted for each parameter to assess and compare the outcomes between the different treatment arms for the primary and secondary outcomes. A total of 11 RCTs were included in this review. The free gingival graft (FGG) showed the best clinical effect for increasing keratinized mucosa width (KMW). When compared in a network, the FGG demonstrated the best treatment ranking of probability results, followed by connective tissue graft (CTG), acellular dermal matrix (ADM), and xenogeneic collagen matrix (XCM). For the parameters 'mucosa thickness' and 'participant satisfaction with aesthetics', the results were CTG > ADM > XCM and XCM > ADM > CTG, respectively. Autogenous tissue grafts (FGG/CTG) demonstrate the best results in increasing KMW and mucosa thickness when compared to the other biomaterials., (Copyright © 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Sticky bone, a growth factor-enriched bone graft matrix, is a promising autologous material for bone tissue regeneration. However, its production is strongly dependent on manual handling steps. In this sense, a new device was developed to simplify the confection of the sticky bone, named Sticky Bone Preparation Device (SBPD ® ). The purpose of this pilot study was to investigate the suitability of the SBPD ® to prepare biomaterials for bone regeneration with autologous platelet concentrates. The SBPD ® allows the blending of particulate samples from synthetic, xenograft, or autogenous bone with autologous platelet concentrates, making it easy to use and avoiding the need of further manipulations for the combination of the materials. The protocol for the preparation of sticky bone samples using the SBPD ® is described, and the resulting product is compared with hand-mixed SB preparations regarding in vitro parameters such as cell content and the ability to release growth factors and cytokines relevant to tissue regeneration. The entrapped cell content was estimated, and the ability to release biological mediators was assessed after 7 days of incubation in culture medium. Both preparations increased the leukocyte and platelet concentrations compared to whole-blood samples ( p < 0.05), without significant differences between SB and SBPD ® . SBPD ® samples released several growth factors, including VEGF, FGFb, and PDGF, at concentrations physiologically equivalent to those released by SB preparations. Therefore, the use of SBPD ® results in a similar product to the standard protocol, but with more straightforward and shorter preparation times and less manipulation. These preliminary results suggest this device as a suitable alternative for combining bone substitute materials with platelet concentrates for bone tissue regeneration.

Osteonecrosis of the jaw is a severe adverse condition affecting patients exposed to specific types of medications. Previous studies have highlighted that osteonecrosis of the jaw is triggered by invasive dental procedures and can be very challenging to manage, especially in patients with cancer. The primary aim of this review was to analyse all available evidence on the management (surgical and/or conservative) of medication related osteonecrosis of the jaws (MRONJ) in patients with a history of antiangiogenic drugs therapy and who had not been previously exposed to any antiresorptive drug treatments. A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until November 2020. Data were extracted from relevant papers and analysed according to the outcomes selected in this review. The search generated 28 studies eligible for the analysis. The total number of patients included in the analysis was 36. Sixteen patients were treated with anti-vascular endothelial growth factor drugs (anti-VEGF) while the remaining patients were administered a combination of antiangiogenic drugs. The most common MRONJ site was the mandible in 29 patients. MRONJ recurrence after treatment was only reported in six patients, the majority of which were treated conservatively. The data reviewed confirmed that an invasive procedure was the most common trigger of MRONJ with relatively high frequency of postoperative recurrence following treatment. However, due to the low quality of available research in the literature, it is difficult to draw a definitive conclusion on the validity of the presented treatment to manage patients affected by MRONJ associated with angiogenic therapy., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

To preserve alveolar bone thickness and width after extraction, clinical strategies have been adopted to reduce or eliminate the need for future surgical interventions to increase the alveolar ridge. The use of xenogeneic biomaterials has been increasing for such application. The association of bone substitutes with active oxygen-based materials, which is essential in the wound-healing process, could accelerate bone repair, optimizing the maintenance of alveolar architecture after extraction. However, the truth of this hypothesis is not clear. The present study aimed to compare the biological response to inorganic bovine bone graft Bonefill (BF), associated or not with active oxygen-based oral gel Bluem (BF+BM), in alveolar bone repair. Twenty female Wistar rats were randomly allocated. The left upper central incisor was extracted, and the dental sockets were filled with BF in the control group (n = 10) and with BF+BM in the experimental group (n = 10). The animals were euthanized at 7 and 42 days after implantation (n = 5), and the samples were processed for descriptive histological and histomorphometric evaluations. The results showed no significant difference between the groups (P > .05). Both groups presented a time-dependent increase in newly formed bone and biosorption biomaterial (P = .0001). The association between active oxygen-based gel and inorganic bovine bone graft did not interfere with or improve bone repair during the experimental periods of alveolar bone repair in rats.

Making an intraoral digital scan for fixed mandibular implant-supported complete-arch prostheses is a clinical challenge. The absence of references in the mandibular arch for precise scan alignment may complicate the correct digital design of the prosthesis framework. This article presents a straightforward method that allows a completely digital approach to digital scanning for fixed mandibular implant-supported prostheses., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Primary implant stability is a prerequisite for successful implant osseointegration. The osseodensification technique (OD) is a non-subtractive drilling technique that preserves the bone tissue, increases osteotomy wall density, and improves the primary stability. This study aimed to investigate the hypothesis that OD, through a wider osteotomy, produces healing chambers (HCs) at the implant-bone interface without impacting low-density bone primary stability. Twenty implants (3.5 × 10 mm) with a nanohydroxyapatite (nHA) surface were inserted in the ilium of ten sheep. Implant beds were prepared as follows: (i) 2.7-mm-wide using subtractive conventional drilling (SCD) technique (n = 10); (ii) 3.8-mm-wide using an OD bur system (n = 10). The sheep were randomized to two groups, with samples collected at either 14-(n = 5) or 28-days (n = 5) post-surgery and processed for histological and histomorphometric evaluation of bone-implant contact (BIC) and bone area fraction occupancy (BAFO). No significant group differences were found with respect to final insertion torque and implant stability quotient (p > 0.050). BIC values were higher for SCD after 14 and 28 days (p < 0.050); however, BAFO values were similar (p > 0.050). It was possible to conclude that the OD technique allowed a wider implant bed preparation without prejudice on primary stability and bone remodeling., (© 2021. The Author(s).)

In daily clinical practice, there is a notable variety of synthetic bone substitute, with various resorption rates, different chemical and structural characteristics that influence on bone regeneration and are not suitable for every clinical use. New biomaterials based on nanotechnology have been developed to be bioabsorbable as new bone is formed. This study intends to evaluate THP-1 cell viability when exposed to extracts of unsintered nanostructured carbonated hydroxyapatite (cHA) microspheres processed at 5 and 37°C compared to sintered hydroxyapatite processed at 90°C. cHA shows, in previous studies, biocompatibility, and better bioabsorption rates, consequently, improve the deposition of new bone and tissue repair. The results demonstrated that the tested biomaterials did not activate inflammatory role through THP-1 cells and did not affect activated macrophages independently of their crystallinities, suggesting their safety and biocompatibility. These results are of fundamental importance for the advancement of research on smart materials, especially in what controls the effect of nanostructured cHA microspheres in the biological environment, seems to be a promising biomaterial in clinical application on regenerative medicine., (© 2020 Wiley Periodicals LLC.)

Aim: This study aimed to evaluate the prevalence of S. pneumoniae colonization in three different sites in healthy adults: nasopharynx, oropharynx and gingival sulcus., Methods: Two-hundred and sixty five adults, aged 20-60 years, who attended dental clinics in one public university (n = 106) and one military institution (n = 159) were enrolled in this study. Pneumococcal detection was performed by direct culture (DC) and PCR for lytA gene after a broth enrichment step. Capsular types were determined by sequential multiplex PCR., Results: We identified 18 (6.8%) pneumococcal carriers among 265 adults by PCR, but only one (0.4%) pneumococcal strain was isolated by DC method. Oropharynx (17; 6.4%) was the main source of S. pneumoniae. Colonization of gingival sulcus and nasopharynx was found in 4 (1.5%) and 2 (0.8%) adults, respectively. Nine distinct capsular types were detected from 9 adults and co-colonization with 2 serotypes was confirmed in 4 (1.5%) subjects. Factors associated with carriage were being females, low level of schooling, non-military and regular medication. We observed a low (6.8%) pneumococcal carriage prevalence, but oropharyngeal samples yielded more sensitive results, especially by the PCR-based detection methodology., Conclusion: Gingival sulcus was found to be a possible reservoir for S. pneumoniae independently of the oropharynx or nasopharynx colonization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This systematic review aimed to review the literature on the coronectomy technique and evaluate the incidence of success and complications as a surgical approach for inferior third molars. Online databases were searched for data on the frequency of inferior alveolar nerve damage, lingual nerve damage, root migration, pain, infection, dry socket, and extraction of the remaining root, and data on the necessity of reintervention were also extracted. Randomized clinical trials, controlled clinical trials, prospective cohort studies, and prospective and retrospective studies with or without the control group were intercepted. This systematic review was registered in PROSPERO (CDR 42020135485). Sixteen papers analyzed 2176 coronectomies in total, and only five of them were judged as appropriate according to methodological quality assessment. The incidence of inferior alveolar nerve injury was documented in 0.59% of the procedures, lingual nerve injury in 0.22%, infection 3.95%, dry socket 1.12%, extraction of the root 5.28%, and reintervention 1.13%. The pain was the most reported, in 22.04% of the population. This study provides an overview of the clinical success and complications of coronectomy, and their prevalence. A coronectomy may be considered a low-risk procedure and an option for treatment to avoid potential damage to nervous structures. However, patients should still undergo a full screening and evaluation of postsurgical procedures.

Objectives: This study aimed to evaluate dimensional changes, level of soft tissue healing, and pain/discomfort perception in post-extraction sockets filling with 1.2% simvastatin (SIM) gel covered with polypropylene membranes (PPPM)., Material and Methods: Twenty-six post-extraction sockets of posterior teeth were randomly allocated in two groups: (a) socket filling with 1.2% SIM gel and covered with PPPM (n = 13) and (b) socket filling with placebo gel and covered with PPPM (n = 13). Cone-beam computed tomography (CBCT) images before and 90 days after the extraction enabled alveolar bone dimensional changes calculation using horizontal and vertical measurements. The measurements occurred at three different levels for thickness located 1, 3, and 5 mm from the top of the bone crest. The vertical (depth) measure was assessed from the most apical portion of the socket to the bone crest's most coronal portion. Seven days after the extractions, the level of soft tissue healing and pain perception were also analyzed., Results: After 90 days of extractions, the dimensional changes in thickness in the test group were significantly smaller in sections A (p = .044), B (p = .036) and C (p = .048) when compared to the control group. The test group showed a significantly lower height-dimensional change than the control group (p < .0001). Soft tissue healing index (p = .63), perception of pain (p = .23), and number of analgesics consumed (p = .25) were similar between groups., Conclusions: Simvastatin at 1.2% compared with placebo effectively reduced the dimensional changes in post-extraction sockets covered with PPPM. There was no significant difference in the level of soft tissue healing and postoperative pain between the test and control groups., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Osteonecrosis of the jaw (ONJ) is reported to be primarily associated with patients receiving bisphosphonate therapies but has been found in patients taking a number of other medications. A number of recent reports have noted the presence of metastatic cancers in the histologic analysis of osteonecrotic lesions from the jaw. The aim of the present review is to estimate the frequency and the type of metastatic cancer most commonly found in ONJ specimens in patients undergoing antiresorptive and/or antiangiogenic drug therapy., Material and Methods: A multidatabase (PubMed, MEDLINE, EMBASE, and CINAHL) systematic search was performed. Any studies involving human participants treated with antiresorptive and antiangiogenic drugs were considered. Where study patients presented with malignant cells within osteonecrotic specimens, further data were collected. Data are presented using descriptive statistics., Results: A total of 13 studies met the inclusion criteria for this systematic review. Thirty-seven study patients had histologic evidence of malignant cells within medication-related osteonecrosis of the jaw (MRONJ) specimens. The most frequent phenotype of malignant cells found within MRONJ specimens were breast cancer variants (n = 15). The frequency of malignant tumor cells found within the MRONJ specimens was calculated using 4 studies. Out of 604 patients, the frequency was 4.64% (n = 28)., Conclusions: Based on the limited data available in the literature, it is plausible that not histologically analyzing all ONJ specimens could result in a small number of undiagnosed and untreated malignant diseases. Additional data based on a larger cohort of study patients is necessary to understand the role of MRONJ in metastatic spread and the influence of surgical treatment and reoccurrence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Guided bone regeneration (GBR) is a process that involves the regeneration of bone defects through the application of occlusive membranes that mechanically exclude the population of non-osteogenic cells from the surrounding soft tissue. Interestingly, platelet-rich fibrin (PRF) has previously been proposed as an autologous GBR membrane despite its short-term resorption period of 2-3 weeks. Recent clinical observations have demonstrated that, by heating a liquid platelet-poor plasma (PPP) layer and mixing the cell-rich buffy coat zone, the resorption properties of heated albumin gel with liquid-PRF (Alb-PRF) can be significantly improved. The aim of this study was to evaluate the inflammatory reaction, biocompatibility, and extended degradation properties of a new autologous Alb-PRF membrane in comparison to commonly utilized standard PRF after nude mice implantation, according to ISO 10993-6/2016. Two standard preparations of PRF (L-PRF and H-PRF) were compared to novel Alb-PRF following subcutaneous implantation at 7, 14, and 21 days. All groups demonstrated excellent biocompatibility owing to their autologous sources. However, it is worth noting that, while both L-PRF and H-PRF membranes demonstrated significant or complete resorption by 21 days, the Alb-PRF membrane remained volume-stable throughout the duration of the study. This study demonstrates-for the first time, to the best of our knowledge-a marked improvement in the membrane stability of Alb-PRF. This indicates its future potential for use as a biological barrier membrane for GBR procedures with a long-lasting half-life, or as a biological filler material in esthetic medicine applications. Thus, further studies are warranted to explore future clinical applications in various fields of medicine.

Objectives: This study aims to compare the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) with other commonly utilized modalities., Materials and Methods: The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 10 categories as follows: (1) open flap debridement (OFD) alone versus OFD/PRF; (2) OFD/bone graft (OFD/BG) versus OFD/PRF; (3) OFD/BG versus OFD/BG/PRF; (4-6) OFD/barrier membrane (BM), OFD/PRP, or OFD/enamel matrix derivative (EMD) versus OFD/PRF; (7) OFD/EMD versus OFD/EMD/PRF; (8-10) OFD/PRF versus OFD/PRF/metformin, OFD/PRF/bisphosphonates, or OFD/PRF/statins. Weighted means and forest plots were calculated for probing depth (PD), clinical attachment level (CAL), and radiographic bone fill (RBF)., Results: From 551 articles identified, 27 RCTs were included. The use of OFD/PRF statistically significantly reduced PD and improved CAL and RBF when compared to OFD. No clinically significant differences were reported when OFD/BG was compared to OFD/PRF. The addition of PRF to OFD/BG led to significant improvements in CAL and RBF. No differences were reported between any of the following groups (OFD/BM, OFD/PRP, and OFD/EMD) when compared to OFD/PRF. No improvements were also reported when PRF was added to OFD/EMD. The addition of all three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements of PD, CAL, and RBF., Conclusions: The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone with similar levels being observed between OFD/BG and OFD/PRF. Future research geared toward better understanding potential ways to enhance the regenerative properties of PRF with various small biomolecules may prove valuable for future clinical applications. Future research investigating PRF at histological level is also needed., Clinical Relevance: The use of PRF in conjunction with OFD statistically significantly improved PD, CAL, and RBF values, yielding to comparable outcomes to OFD/BG. The combination of PRF with bone grafts or small biomolecules may offer certain clinical advantages, thus warranting further investigations.

Objectives: To present and explore the potential of an animal-based experimental model developed to determine the set of root canal sealers in vivo. The setting of AH Plus, BioC Sealer, TotalFill BC Sealer, and Sealapex was determined using either ISO 6876 or the novel in vivo method proposed in this study., Material and Methods: The in vitro setting time of the sealers tested was determined in accordance with ISO 6876:2012. In determining the in vivo set, 24 adult Wistar rats were followed up for two evaluation periods: 1 and 4 weeks. Their upper-right incisor was extracted, and its pulp tissue was removed. The root canal was then filled from retrograde with one of the 4 sealers, and the tooth was re-implanted and fixed with a layer of a flowable composite resin. After 1 or 4 weeks of the surgical procedures, the animals were euthanized, and their incisors were extracted. Two-mm-thick slices of the middle third of the tooth root were obtained and assessed with a Gillmore device, to determine whether or not the sealer had set., Results: The following in vitro results were obtained by using ISO 6876 methodology: AH Plus set after a mean time of 423 ± 20 min and 476 ± 35 min, in metal and plaster molds, respectively. BioC Sealer set after 7 days (in dental plaster molds), whereas TotalFill BC Sealer and Sealapex did not set even after 25 days in both tested conditions (metal or dental plaster molds). Using the novel in vivo methodology, AH Plus, BioC Sealer, and TotalFill BC Sealer set after both 7 and 30 days. In contrast, Sealapex did not set at either time point., Conclusions: AH Plus and BioC Sealer set under both in vitro and in vivo test conditions. TotalFill BC Sealer did not set under in vitro conditions but did after 1 week under in vivo conditions. Sealapex did not set under either in vitro or in vivo conditions., Clinical Relevance: The influence of the testing conditions on the setting results is a clear indication that new in vivo experimental models should be useful in future studies on Bioceramics root canal sealers.

Medication related osteonecrosis of the jaw (MRONJ) is a severe condition affecting the jaws of patients exposed to specific drugs, and is primarily described in patients receiving bisphosphonate (BP) therapy. However, more recently it has been observed in patients taking other medications, such as the RANK ligand inhibitor (denosumab) and antiangiogenic drugs. It has been proposed that the existence of other concomitant medical conditions may increase the incidence of MRONJ. The primary aim of this research was to analyze all available evidence and evaluate the reported outcomes of osteonecrosis of the jaws (ONJ) due to antiresorptive drugs in immunosuppressed patients. A multi-database (PubMed, MEDLINE, EMBASE and CINAHL) systematic search was performed. The search generated twenty-seven studies eligible for the analysis. The total number of patients included in the analysis was two hundred and six. All patients were deemed to have some form of immunosuppression, with some patients having more than one disorder contributing to their immunosuppression. Within this cohort the commonest trigger for MRONJ was a dental extraction (n=197). MRONJ complications and recurrence after treatment was sparsely reported in the literature, however a total of fourteen cases were observed. The data reviewed have confirmed that an invasive procedure is the commonest trigger of MRONJ with relatively high frequency of post-operative complications or recurrence following management. However, due to low-quality research available in the literature it is difficult to draw a definitive conclusion on the outcomes analysed in this systematic review., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Research in Medical Sciences.)

This systematic review (SR) aimed to evaluate implant survival rate, marginal bone loss (MBL), and biological/prosthetic complications of extra-short 4 mm dental implants. An electronic search without language or date restrictions was performed in five databases and in gray literature for articles published until August 2020. Prospective cohort studies and randomized clinical trials (RCTs) that evaluated the clinical performance of extra-short 4 mm dental implants were included. Studies were independently assessed for risk of bias using the Cochrane Collaboration's tool. The protocol of this SR was registered in the PROSPERO database under number CRD42019139709. Four studies were included in the present SR. There was no significant difference in implant survival rate ( p = 0.75) between extra-short 4 mm and long implants. After 12 months of function, the extra-short implants had a significantly ( p = 0.003) lower marginal bone loss (MBL) rate when compared to long implants. Extra-short implants had a lower number of biological and prosthetic complications when compared to long implants. After 12 months of follow-up, extra-short 4 mm dental implants placed in the mandible exhibit satisfactory clinical outcomes concerning implant survival rate and MBL when compared to longer implants, with a low number of biological and prosthetic complications. A higher number of RCTs with longer follow-up is necessary for the future.

Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is rare. It is a serious adverse effect of certain drugs, of which bisphosphonates (BPs) are the most widely known. The aim of this systematic review was to analyze all published evidence for the reported adverse outcomes as a result of orthodontic treatment in patients undergoing antiresorptive therapy., Data: All types of studies involving patients undergoing orthodontic treatment and treated with antiresorptive drugs were considered. A meta-analysis was not conducted due to the high amount of variability and heterogeneity in the reporting and presentation of data among the studies meeting the inclusion criteria., Sources: A systematic search was performed using 4 databases (PubMed, MEDLINE, EMBASE and CINAHL)., Study Selection: Seven studies matched the inclusion criteria for this review, reporting a total of 29 patients. MRONJ was only reported in 1 patient. The adverse outcomes following orthodontic treatment included difficulty achieving root parallelism ( n = 4), difficulty achieving complete space closure ( n = 3), exaggerated tooth mobility post-debond ( n = 2), increased duration of orthodontic treatment beyond expected completion ( n = 1), sclerotic alveolar bone changes seen on post-op radiographic images ( n = 2), and an increased amount of root resorption ( n = 1)., Conclusions: The high amount of heterogeneity and limited evidence precluded a valid interpretation and analysis of the results through pooling of data. Additional data with sufficient quality, a reduction of bias, and a greater prospective cohort of patients is crucial to assess adverse effects, mechanisms of action, and associated risk factors in at-risk patients., Clinical Significance: Based on the limited evidence available in the literature, it is unclear whether orthodontic treatment alone can precipitate MRONJ. However, antiresorptive drug therapy may be associated with a sub-optimal treatment outcome., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Synthetic biphasic calcium phosphate (BCP) granules and powder are biocompatible biomaterials with a well-known capacity for osteoconduction, presenting very satisfactory clinical and histological results. It remains unanswered if the putty configuration impacts the biological response to the material. In this study, we aimed to compare the cytocompatibility and biocompatibility of nanostructured BCP in the putty configuration (moldable nanostructured calcium phosphate, MnCaP) on the healing of critical-sized bone defects (8 mm) in rat calvaria. Cytocompatibility was determined through the viability of fibroblast cells (V-79) to the extracts of different concentrations of MnCaP. Forty-five Wistar rats were randomly divided into three groups ( n = 15)-clot, MnCaP, and commercial biphasic calcium phosphate in granules configurations (Nanosynt ® )-and subdivided into three experimental periods (1, 3, and 6 months). Histological, histomorphometric, and microtomographic analyses allowed the evaluation of newly formed bone, residual biomaterial, and connective tissue. The in vitro evaluation showed that MnCaP was cytocompatible. The histomorphometric results showed that the Nanosynt ® group granted the highest new-formed bone values at six months ( p < 0.05), although the biomaterial volume did not differ between groups. The putty configuration was easier to handle, and both configurations were biocompatible and osteoconductive, presented similar biosorption rates, and preserved the calvaria architecture.

Background: Although several therapies are proposed for medication-related osteonecrosis of the jaw (MRONJ), to date there is no consensus or treatment protocol for MRONJ. This overview aims to summarize the available evidence on the management and outcomes of MRONJ., Methods: An electronic search without language or date restrictions occurred in five databases and gray literature for articles published until March 2020. This overview was performed according to the PICO format. The eligibility criteria comprised systematic reviews (RS) with or without meta-analyses that analyzed treatments outcomes for MRONJ. The methodological quality of each SR was evaluated using AMSTAR 2., Results: Fifteen studies published between 2014 and 2020 were included in this overview. The summary of the evidence showed that conservative treatment and low level laser therapy can yield favorable results for early stages of MRONJ whereas surgical treatment seems to be better for advanced stages. However, qualitative assessment of the SRs highlighted a global low level of quality., Conclusions: There is weak evidence to support treatment protocols for MRONJ. Because of the low quality of the SRs, highlighted by this overview, no insightful therapeutic recommendations can be issued for any intervention for MRONJ., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Orbital fractures alone represent 10% up to 25% of all facial fractures, but when they are associated with other fractures of the middle-third of the face, their incidence can increase up to 55%. This study aimed to identify whether the size of the orbital defect based on the classification by Jaquiéry et al. influenced the resolution of post-traumatic complications after orbital wall reconstruction using PRECLUDE®MVP alone or in combination with a titanium mesh or autogenous bone graft. Thirty-five orbits were categorized into four groups on the basis of the size of the defect and the operative techniques: group 1 contained 16 Jaquiéry class I orbits treated only with PRECLUDE®MVP; group 2 included eight class II orbits treated with PRECLUDE®MVP along with autogenous bone graft harvested from the calvaria or a titanium mesh; group 3 included five class III orbits and group 4 included six class IV orbits that were treated the same way as those in group 2. Spearman correlation showed that the use PRECLUDE®MVP didn't improve the post traumatic complications for big orbital defects due to the three-dimensional anatomical changes that occurred by neurologic lesions and lipolysis of the orbital contents., Competing Interests: The authors have no conflict of interest., (© 2021 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.)

This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods ( p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity.

Mechanical barriers prevent the invasion of the surrounding soft tissues within the bone defects. This concept is known as Guided Bone Regeneration (GBR). The knowledge about the local tissue reaction and the time of degradation of absorbable membranes favors the correct clinical indication. This study aimed to evaluate the biocompatibility and biodegradation of a bovine collagen membrane (Lyostypt ® , São Gonçalo, Brazil) and compare it to a porcine collagen membrane (Bio-Gide ® ) implanted in the subcutaneous tissue of mice, following ISO 10993-6:2016. Thirty Balb-C mice were randomly divided into three experimental groups, LT (Lyostypt ® ), BG (Bio-Gide ® ), and Sham (without implantation), and subdivided according to the experimental periods (7, 21, and 63 days). The BG was considered non-irritant at seven days and slight and moderate irritant at 21 and 63 days, respectively. The LT presented a small irritant reaction at seven days, a mild reaction after 21, and a reduction in the inflammatory response at 63 days. The biodegradation of the LT occurred more rapidly compared to the BG after 63 days. This study concluded that both membranes were considered biocompatible since their tissue reactions were compatible with the physiological inflammatory process; however, the Bio-Gide ® was less degraded during the experimental periods, favoring the guided bone regeneration process.

Many biomaterials are used for Bone Morphogenetic Proteins (BMPs) delivery in bone tissue engineering. The BMP carrier system's primary function is to hold these growth factors at the wound's site for a prolonged time and provide initial support for cells to attach and elaborate the extracellular matrix for bone regeneration. This study aimed to evaluate the nanostructured carbonated hydroxyapatite microspheres (nCHA) as an rhBMP-2 carrier on rats calvaria. A total of fifteen male Wistar rats were randomly divided into three groups ( n = 5): clot (control group), rhBMP-2 associated with collagen membrane (COL/rhBMP-2) or associated with the microspheres (nCHA/rhBMP-2). After 45 days, the calvaria defect samples were evaluated through histological, histomorphometric, and SR-µCT analyses to investigate new-formed bone and connective tissue volume densities. The descriptive histological analysis showed that nCHA/rhBMP-2 improved bone formation compared to other groups. These results were confirmed by histomorphometric and SR-µCT analysis that showed substantially defect area filling with a higher percentage of newly formed (36.24 ± 6.68) bone than those with the COL/rhBMP-2 (0.42 ± 0.40) and Clot (3.84 ± 4.57) ( p < 0.05). The results showed that nCHA is an effective carrier for rhBMP-2 encouraging bone healing and an efficient alternative to collagen membrane for rhBMP-2 delivery.

Objectives: This study aimed to conduct a network comparison of the clinical effect of connective tissue graft (CTG) substitutes on the treatment of gingival recessions using coronally advanced flap., Materials and Methods: An electronic search without language or dates restrictions was performed in five databases and in Grey literature for articles published until May, 2020. The eligibility criteria comprised randomized controlled trials (RCTs) that analyzed the clinical outcomes of CTG substitutes when compared with coronally advanced flap (CAF) for the treatment of Miller class I and II (Cairo RT I) gingival recessions. A pairwise and network meta-analysis were conducted for each periodontal parameters to assess and compare the outcomes among different treatment arms for the primary and secondary outcomes. This systematic review (SR) was registered in INPLASY under number INPLASY202060075., Results: Twenty-seven studies were included in the present SR. All analyzed CTG substitutes showed superior results when comparing with CAF alone for all periodontal parameters. However, when compared in a network, the acellular dermal matrix (ADM) demonstrated the best treatment ranking of probability results, followed by platelet-rich fibrin (PRF), enamel matrix derivative (EMD), and xenogeneic collagen matrix (XCM) for root coverage (RC)., Conclusion: This SR observed that the association of biomaterials increases the effectiveness of RC in comparison with CAF alone. Based on the treatment ranking, although all the biomaterials analyzed showed a positive effect for RC, the ADM demonstrated the best results., Clinical Relevance: To know the effectiveness of CTG substitutes for the treatment of gingival recessions.

Background and Objectives: There is still considerable controversy regarding the possibility of submitting replanted teeth to orthodontic movement (OM). The purpose of the present study was to evaluate the tissue response after orthodontic movement on replanted teeth. Materials and Methods: Sixty Wistar rats were randomly assigned to four groups ( n = 15): G1, replantation without OM after 30 days; G2, replantation with OM after 30 days; G3, replantation without OM after 60 days, and G4, replantation with OM after 60 days. The maxillary left central incisors were extracted and the teeth were stored in milk media. After 30 min, the teeth were replanted and fixed with non-rigid immobilization. All specimens were observed after 30 and 60 days of replantation and then subdivided into two subgroups (with OM or without OM). The animals were euthanized after seven days of the OM started, and the maxillary bone blocks were processed for histological evaluation. Results: The histological results showed periodontal ligament repair in both periods studied without OM; however, ankylosis and root resorption was seen in all orthodontically moved teeth. Conclusions: The orthodontic movement did not favor tissue response in all replanted teeth, regardless of the experimental periods.

Zinc is an important element for bone structure and metabolism. Its interaction with hydroxyapatite has been investigated for the improvement of bone repair. The objective of this study was to evaluate the in vitro and in vivo biological response to nanostructured calcium alginate-hydroxyapatite (HA) and zinc-containing HA (ZnHA). Cytocompatibility was evaluated by applying PrestoBlue reagent after exposing murine pre-osteoblast cells to extracts of each biomaterial microspheres. After physical and chemical characterization, the biomaterial microspheres were implanted in a critical size calvaria defect (8 mm) in Wistar rats (n = 30) that were randomly divided into the HA and ZnHA groups. Tissue samples were evaluated through histological and histomorphometric analyses after 1, 3, and 6 months (n = 5). The results showed cellular viability for both groups compared to the negative control, and no differences in metabolic activity were observed. The HA group presented a significant reduction of biomaterial compared with the ZnHA group in all experimental periods; however, a considerable amount of new bone formation was observed surrounding the ZnHA spheres at the 6-month time point compared with the HA group (p < .05). Both biomaterials were biocompatible, and the combination of zinc with hydroxyapatite was shown to improve bone repair., (© 2020 Wiley Periodicals, Inc.)

The apoptosis-associated Speck-like protein containing a caspase-1 recruitment domain (ASC), present in inflammasomes, regulates inflammation events and is involved in osteogenic phenotype. Nevertheless, its function in bone repair induced by bone substitute biomaterials is unclear. This study aimed to unveil the role of ASC on osteoprogenitor and tissue response to stoichiometric-hydroxyapatite (HA), nanostructured carbonated-hydroxyapatite (CHA), and CHA containing 5% Strontium (SrCHA), characterized previously by XRD, uXRF-SR, and FTIR spectroscopy implants. Thereafter, conditioned media by the biomaterials were used later to treat pre-osteoblasts and an osteogenic stimulus was shown in response to the materials, with higher expression of Runx2, Osterix, ALP, and Collagen 1a1 genes, with significant involvement of inflammatory-related genes. Thus, to better address the involvement of inflammasome, primary cells obtained from both genotypes [Wild-Type (WT) and ASC Knockout (ASC-KO) mice] were subjected to conditioned media up to 7 days, and our data reinforces both HA and CHA induces lower levels of alkaline phosphatase (ALP) than SrCHA, considering both genotypes (p < 0.01), and ASC seems contribute with osteogenic stimulus promoted by SrCHA. Complimentarily, the biomaterials were implanted into both subcutaneous and bone defects in tibia. Histological analysis on 28 days after implantation of biomaterials into mice's subcutaneous tissue revealed moderate inflammatory response to them. Both histomorphometry and μCT analysis of tibias indicated that the biomaterials did not reverse the delay in bone repair of ASC KO, reinforcing the involvement of ASC on bone regeneration and bone de novo deposition. Also, the bone density in CHA was >2-fold higher in WT than ASC-KO samples. HA was virtually not resorbed throughout the experimental periods, in opposition to CHA in the WT group. CHA reduced to half-area after 28 days, and the bone deposition was higher in CHA for WT mice than HA. Taken together, our results show that biomaterials did not interfere with the healing pattern of the ASC KO, but CHA promoted higher bone deposition in the WT group, probably due to its greater biodegradability. These results reinforce the importance of ASC during bone de novo deposition and healing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the clinical effects of xenogeneic collagen matrix (XCM) in augmenting keratinized mucosa width (KMW) around dental implants., Materials and Methods: Articles that were published before or during April 2020 were electronically searched in four databases without any date or language restrictions and manually searched in regular journals and grey literature. The eligibility criteria comprised randomized controlled trials (RCTs) or prospective studies that analysed the clinical efficacy of XCM for augmenting KMW around dental implants. This systematic review (SR) was registered in PROSPERO under number CRD42018115399., Results: Eleven studies published between 2009 and 2019 were included in this SR. There was no significant difference in KMW increase (p = 0.14), probing depth (PD) decrease (p = 0.17) or participants' aesthetic satisfaction (PAS) (p = 0.32) when XCM was compared to connective tissue graft (CTG). However, the increase in gingival thickness (GT) was significantly higher (p = 0.001) with the use of CTG., Conclusions: The use of XCM improved KMW and PD with rates comparable to those for CTG. XCM showed lower results for GT when compared to CTG. XCM presented similar results in terms of PAS when compared to CTG., Clinical Relevance: The presence of a KMW around dental implants is associated with better peri-implant tissue health.

Among the biomaterials based on calcium phosphate, hydroxyapatite has been widely used due to its biocompatibility and osteoconduction. The substitution of the phosphate group by the carbonate group associated with the absence of heat treatment and low synthesis temperature leads to the formation of carbonated hydroxyapatite (CHA). The association of CHA with other metals (strontium, zinc, magnesium, iron, and manganese) produces amorphous calcium phosphate-containing metals (ACPMetals), which can optimize their properties and mimic biological apatite. This study aimed to evaluate the biocompatibility and biodegradation of ACPMetals in mice subcutaneous tissue. The materials were physicochemically characterized with Fourier Transform InfraRed (FTIR), X-Ray Diffraction (XRD), and Atomic Absorption Spectrometry (AAS). Balb-C mice ( n = 45) were randomly divided into three groups: carbonated hydroxyapatite, CHA ( n = 15), ACPMetals ( n = 15), and without implantation of material (SHAM, n = 15). The groups were subdivided into three experimental periods (1, 3, and 9 weeks). The samples were processed histologically for descriptive and semiquantitative evaluation of the biological effect of biomaterials according to ISO 10993-6:2016. The ACPMetals group was partially biodegradable; however, it presented a severe irritating reaction after 1 and 3 weeks and moderately irritating after nine weeks. Future studies with other concentrations and other metals should be carried out to mimic biological apatite.