The efficacy of combining adjuvants with non-surgical periodontal therapy in individuals with type 2 diabetes: A Bayesian network meta-analysis.

AIM: This Bayesian network meta-analysis of randomized controlled trials assessed the effect of adjuvant periodontal treatment in both periodontal and HbA1c outcomes in adult individuals with type 2 diabetes (T2DM). MATERIALS AND METHODS: A systematic search was done up to February 2023 comparing sub-gingival debridement (SD) in combination with local or systemic adjuvant treatment with SD alone for individuals with T2DM. The primary outcomes were changes in absolute HbA1c levels and full-mouth probing depth reported at 3- to 6-month post-treatment. RESULTS: Seventy-two eligible publications evaluating 27 adjuvant treatments were retrieved. The combination of SD and systemic antibiotic metronidazole or SD and antioxidant alpha lipoic acid provided, respectively, 1.4% (95% credible interval [CrI] 0.48; 2.20) and 2.4% (95% CrI 1.50; 3.30) more significant improvement on HbA1c levels, and 0.89 mm (95% CrI 0.23; 1.50) and 0.92 mm (95% CrI 0.02; 0.92) greater periodontal probing depth reductions. Other adjuvant treatments provided added benefit to the periodontal outcomes without discernible effects on HbA1c. CONCLUSIONS: Adjuvant use of metronidazole or alpha lipoic acid was the best adjunct option to provide clinically meaningful HbA1c levels and probing depth reductions. However, no strong recommendation can be drawn due to the scarcity of studies for each adjuvant treatment and the low certainty of the resultant evidence.

Mitigation of BMP-induced inflammation in craniofacial bone regeneration and improvement of bone parameters by dietary hesperidin.

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n = 10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 µg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14 post-surgery. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested at day 14 were subjected to microcomputed tomography and histology. HE + BMP2-treated rats had a statistically significant decrease in expression of inflammatory genes compared to BMP2 alone. The high-dose BMP2 alone caused cystic-like regeneration with incomplete defect closure. HE + BMP2 showed virtually complete bone fusion. Collagen fibril birefringence pattern (red color) under polarized light indicated high organization in BMP2-induced newly formed bone (NFB) in HE-supplemented group (p < 0.05). Clear changes in osteocyte lacunae as well as a statistically significant increase in osteoclasts were found around NFB in HE-treated rats. A significant increase in trabecular volume and thickness, and trabecular and cortical density was found in femurs of HE-supplemented rats (p < 0.05). Our findings show, for the first time, that dietary HE has a remarkable modulatory role in the function of locally delivered high-dose BMP2 in bone regeneration possibly via control of inflammation, osteogenesis, changes in osteocyte and osteoclast function and collagen maturation in regenerated and native bone. In conclusion, HE had a significant skeletal bone sparing effect and the ability to provide a more effective BMP-induced craniofacial regeneration.

Perception of COVID-19 pandemic restrictions on dental researchers.

BACKGROUND/OBJECTIVES: Historical evidence shows a gender-based disproportionate effect of pandemics across different populations. In 2020, the coronavirus disease 2019 (COVID-19) pandemic began spreading its devastating effects worldwide. The goal of the present study was to investigate the effect of the COVID-19 pandemic on research productivity, work-life arrangements, and mental health of dental professionals worldwide with focus on gender differences. METHODS: A 38-item survey, concerning demographics, career stage, employer support, family structure, mental health, and relationships, was distributed to 7692 active members of the International Association for Dental Research. Bivariate associations between independent variables and the primary outcome variable were tested using Spearman's correlation test. A logistic regression model was used to assess the simultaneous, independent associations between each variable and researcher productivity. RESULTS: A total of 722 responses were obtained, indicating a 9.4% response rate. Higher productivity was reported by male respondents (p = 0.021), and by those in senior career stages (p = 0.001). Institutional support was associated with higher productivity (p < 0.0001). Lower productivity was reported by younger researchers (p = 0.003). Remote work negatively affected productivity (p < 0.0001) and female respondents reported working more hours, regardless of work location (p = 0.004). Poor mental health was associated with low productivity (p < 0.0001). CONCLUSIONS: Our results showed that the COVID-19 pandemic significantly affected dental professionals' perceived productivity and mental health around the globe. Younger individuals and women were disproportionally affected, and institutional support had a significant influence to mitigate effects of the pandemic for dental researchers.

Biomimetic polydopamine-laced hydroxyapatite collagen material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts.

Polydopamine-assisted modification for bone substitute materials has recently shown great application potential in bone tissue engineering due to its excellent biocompatibility and adhesive properties. A scaffold material's impact on osteoclasts is equally as important as its impact on osteoblasts when considering tissue engineering for bone defect repair, as healthy bone regeneration requires an orchestrated coupling between osteoclasts and osteoblasts. How polydopamine-functionalized bone substitute materials modulate the activity of osteoblast lineage cells has been extensively investigated, but much less is known about their impact on osteoclasts. Moreover, most of the polydopamine-functionalized materials would need to additionally load a biomolecule to exert the modulation on osteoclast activity. Herein, we demonstrated that our biomimetic polydopamine-laced hydroxyapatite collagen (PDHC) scaffold material, which does not need to load additional bioactive agent, is sufficiently able to modulate osteoclast activity in vitro. First, PDHC showed an anti-resorptive potential, characterized by decreased osteoclast differentiation and resorption capacity and changes in osteoclasts' transcriptome profile. Next, cAMP response element-binding protein (CREB) activity was found to mediate PDHC's anti-osteoclastogenic effect. Finally, although PDHC altered clastokines expression pattern of osteoclasts, as revealed by transcriptomic and secretomic analysis, osteoclasts' coupling to osteoblasts was not compromised by PDHC. Collectively, this study demonstrated the PDHC material orients osteoclast behavior to an anti-resorptive pattern without compromising osteoclasts' coupling to osteoblasts. Such a feature is favorable for the net increase of bone mass, which endows the PDHC material with great application potential in preclinical/clinical bone defect repair.

Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo.

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.

Effect of Flavonoid Supplementation on Alveolar Bone Healing-A Randomized Pilot Trial.

We investigated the effects of two common dietary supplements on bone healing in dental extraction sockets in humans. In this randomized pilot trial, male subjects took Grape Seed Extract [GSE] or Grapefruit Extract [GFE] starting two weeks prior to dental extraction and maintained this regimen for sixty days after surgery. Extraction sockets were filled with a collagen plug. After 24 h, a socket sample was collected and processed for quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and an 84-gene wound healing assay. Sixty days after tooth extraction, a core of newly formed bone was obtained prior to dental implant placement and processed for histology. qRT-PCR revealed that GFE led to a significant decrease in platelet-derived growth factor and interleukin (IL)1-ß compared to GSE, and a significant decrease in IL-6 and CXCL2 compared to control. GSE led to a significant increase in coagulation factor Von Willebrand and inflammatory marker IL1-ß compared to GFE. WISP1 and CXCL5 were upregulated in both groups. Overall, GFE showed a downregulation of inflammation and GSE led to a decrease in collagen density and increased osteoclasts. This pilot trial highlights the need for further investigation on the mechanism of action of such supplements on bone healing and oral health.

Global deletion of Optineurin results in altered type I IFN signaling and abnormal bone remodeling in a model of Paget's disease.

Genome-wide association studies (GWAS) have identified Optineurin (OPTN) as genetically linked to Paget's disease of the bone (PDB), a chronic debilitating bone remodeling disorder characterized by localized areas of increased bone resorption and abnormal bone remodeling. However, only ~10% of mouse models with a mutation in Optn develop PDB, thus hindering the mechanistic understanding of the OPTN-PDB axis. Here, we reveal that 100% of aged Optn global knockout (Optn-/-) mice recapitulate the key clinical features observed in PDB patients, including polyostotic osteolytic lesions, mixed-phase lesions, and increased serum levels of alkaline phosphatase (ALP). Differentiation of primary osteoclasts ex vivo revealed that the absence of Optn resulted in an increased osteoclastogenesis. Mechanistically, Optn-deficient osteoclasts displayed a significantly decreased type I interferon (IFN) signature, resulting from both defective production of IFNß and impaired signaling via the IFNα/ßR, which acts as a negative feedback loop for osteoclastogenesis and survival. These data highlight the dual roles of OPTN in the type I IFN response to restrain osteoclast activation and bone resorption, offering a novel therapeutic target for PDB. Therefore, our study describes a novel and essential mouse model for PDB and define a key role for OPTN in osteoclast differentiation.

Evidence of biglycan structure-function in bone homeostasis and aging.

Purpose: Biglycan is a proteoglycan of the small leucine-rich repeat family. It is present in all connective tissues and plays key structural and signaling roles. This review aimed to compile available evidence in the characteristics and distribution of biglycan and its glycosylated and non-glycosylated forms in connective tissues with a specific focus on the contribution to homeostasis of bone and changes of biglycan structure with aging.Methods: The Pubmed database was searched and included the terms "biglycan", "proteoglycans", "glycosaminoglycans", "bone", "osteoblast", "osteocyte", "osteoclast", "aging", "inflammation", "cartilage". Abstracts were appraised and a series of original articles and reviews studied to generate this narrative review.Results: Based on the search, biglycan significantly affects bone development and homeostasis and can be significantly changed by the aging process in several connective tissues, which in turn affects the behavior of tissue and cell responses in aged networks. Further, as the understanding of the various forms of biglycan in vivo is expanded and the function of its components in vitro is dissected, this proteoglycan can potentially serve as a therapeutic or biomarker molecule to detect tissue destruction.Conclusions: Biglycan is a key player in skeletal bone homeostasis, and overall, there is more evidence on the role of biglycan in development and less in the adult physiological or diseased young and aged systems. Further understanding of its conformation, degradation peptides and post-translational modifications will be required to understand the role of biglycan in bone maintenance and to support the development of treatments for age-related bone dysfunctions.

Identification of the effector domain of biglycan that facilitates BMP-2 osteogenic function.

We have reported that recombinant biglycan (BGN) core protein accelerates bone formation in vivo by enhancing bone morphogenetic protein (BMP)-2 function. The purpose of the present study was to identify the specific domain ("effector") within the BGN core protein that facilitates BMP-2 osteogenic function. Thus, we generated various recombinant and synthetic peptides corresponding to several domains of BGN, and tested their effects on BMP-2 functions in vitro. The results demonstrated that the leucine-rich repeats 2-3 domain (LRR2-3) of BGN significantly enhanced the BMP-2 induced Smad1/5/9 phosphorylation, osteogenic gene expression, and alkaline phosphatase activity in myogenic C2C12 cells. Furthermore, addition of LRR2-3 to osteoblastic MC3T3-E1 cells accelerated in vitro mineralization without compromising the quality of the mineral and matrix. These data indicate that LRR2-3 is, at least in part, responsible for BGN's ability to enhance BMP-2 osteogenic function, and it could be useful for bone tissue regeneration.

Effect of Phosphorylated Chitosan on Dentin Erosion: An in vitro Study.

The aim of this study was to evaluate the antierosive effect of phosphorylated chitosan in dentin. Bovine dentin specimens were randomly distributed into the following groups: (1) no treatment (NoTx/negative control), (2) phosphate-buffered saline solution (PBS), (3) AmF/NaF/SnCl2 (positive control), (4) 0.5% chitosan solution (Chi), (5) 0.5% neutral phosphorylated (NP)-Chi, and (6) 0.5% alkaline phosphorylated (AP)-Chi. The specimens were submitted to de-remineralization treatment cycles for 5 days: 0.5% citric acid (2 min), remineralizing solution (30 min), and surface treatment according to assigned groups (2 min, 6×/day). The loss of dentin surface was measured by profilometry. Hardness and modulus of elasticity were measured using a nanoindenter equipped with a Berkovich diamond tip. The dentin surface was analyzed by scanning electron microscopy (SEM). The largest loss of dentin was observed in the No Tx and PBS groups (approx. 25 µm). The group treated with AmF/NaF/SnCl2 showed less loss of dentin (67% reduction vs. NoTx and PBS), followed by the groups treated with NP-Chi and AP-Chi (33% reduction), and Chi (18% reduction). Nanohardness and modulus of elasticity were similar in the NoTx and PBS groups, with a small increase in stiffness in all other groups. SEM revealed that the experimental solution of AP-Chi had a favorable effect on maintaining the integrity of collagen fibrils. AmF/NaF/SnCl2 showed a preserved mineralized collagen surface. Further studies are warranted to explore this nontoxic phosphorylated chitosan polymer as an effective agent in the prevention and treatment of dental erosion.

Characterization of genipin-modified dentin collagen.

Application of biomodification techniques to dentin can improve its biochemical and biomechanical properties. Several collagen cross-linking agents have been reported to strengthen the mechanical properties of dentin. However, the characteristics of collagen that has undergone agent-induced biomodification are not well understood. The objective of this study was to analyze the effects of a natural cross-linking agent, genipin (GE), on dentin discoloration, collagen stability, and changes in amino acid composition and lysyl oxidase mediated natural collagen cross-links. Dentin collagen obtained from extracted bovine teeth was treated with three different concentrations of GE (0.01%, 0.1%, and 0.5%) for several treatment times (0-24 h). Changes in biochemical properties of NaB(3)H4-reduced collagen were characterized by amino acid and cross-link analyses. The treatment of dentin collagen with GE resulted in a concentration- and time-dependent pigmentation and stability against bacterial collagenase. The lysyl oxidase-mediated trivalent mature cross-link, pyridinoline, showed no difference among all groups while the major divalent immature cross-link, dehydro-dihydroxylysinonorleucine/its ketoamine in collagen treated with 0.5% GE for 24 h, significantly decreased compared to control (P < 0.05). The newly formed GE-induced cross-links most likely involve lysine and hydroxylysine residues of collagen in a concentration-dependent manner. Some of these cross-links appear to be reducible and stabilized with NaB(3)H4.

Critical appraisal: Cross-linkers and the dentin matrix.

The formation of a hybrid layer is essential for successful dentin bonding and is achieved by adhesive penetration between exposed collagen fibrils in the demineralized dentin. Incomplete infiltration of the adhesive within the collagen network results in exposed fibrils, which may suffer enzymatic degradation over time. Methods to increase collagen resistance to proteinases (enzymes that degrade proteins) have been studied. One particular approach is to use collagen cross-linking agents that modify collagen through addition of specific or random amino acid linkage between and within its molecules. This Critical Appraisal provides information on the effects of various cross-linkers on dentin collagen stability, dentin properties, and resin-dentin bond strengths, and calls for critical thinking on the potential effects of this therapeutic approach.

Safety and efficacy of a high-adhesion whitening strip under extended wear regimen.

OBJECTIVES: This randomized, parallel group, single centre clinical trial was conducted to evaluate the safety and compare the whitening efficacy for an extended wear of an experimental 9.5% H2O2 high-adhesion whitening strip, relative to a marketed 10% H2O2 control strip. METHODS: Twenty-nine eligible adult volunteers were randomly assigned to either a treatment series with an experimental 9.5% H2O2 high-adhesion whitening strip at home for 2h, once a day, for 8 days; or a marketed 10% H2O2 whitening strip for 30 min, on a similar daily regimen. Tooth color/whitening progression was recorded under standardized lighting conditions at baseline, day 3, day 5, and day 9, via digital imaging. Outcomes were reported using the CIELAB system. Usage safety was also assessed at each follow-up visit. Whitening efficacy for each group was investigated using a paired-difference t-test. The treatment groups were compared among each other using the analysis of covariance, with the baseline value and age as the covariates. RESULTS: Both treatment groups demonstrated statistically significant mean color improvement from baseline for b* (yellow ness) and L* (lightness) at each post-baseline visit. In addition, the 2-h high-adhesion strips demonstrated significantly greater improvement in b* and L* relative to the 30-min strip group at each follow-up visit. CONCLUSIONS: The 2-h regimen for the 9.5% H2O2 high-adhesion whitening strip was more efficient for tooth whitening than the 30-min regimen of 10% H2O2 whitening strip. Both treatments were well tolerated and the use of the test products during the study time frame was considered safe. CLINICAL RELEVANCE: Extending the daily wear time of whitening strips can improve the efficacy of the treatment and ultimately shorten the length of the treatment without any significant adverse effects.

Titanium surface topography affects collagen biosynthesis of adherent cells.

Collagen-dependent microstructure and physicochemical properties of newly formed bone around implant surfaces represent key determinants of implant biomechanics. This study investigated the effects of implant surface topography on collagen biosynthesis of adherent human mesenchymal stem cells (hMSCs). hMSCs were grown for 0 to 42 days on titanium disks (20.0 × 1.0 mm) with smooth or rough surfaces. Cell attachment and spreading were evaluated by incubating cells with Texas-Red-conjugated phalloidin antibody. Quantitative real-time PCR was used to measure the mRNA levels of Col1α1 and collagen modifying genes including prolyl hydroxylases (PHs), lysyl oxidases (LOXs) and lysyl hydroxylases (LHs). Osteogenesis was assessed at the level of osteoblast specific gene expression and alizarin red staining for mineralization. Cell layer-associated matrix and collagen content were determined by amino acid analysis. At 4h, 100% cells were flattened on both surfaces, however the cells on smooth surface had a fibroblast-like shape, while cells on rough surface lacked any defined long axis. PH, LH, and most LOX mRNA levels were greater in hMSCs grown on rough surfaces for 3 days. The mineralized area was greater for rough surface at 28 and 42 days. The collagen content (percent total protein) was also greater at rough surface compared to smooth surface at 28 (36% versus 26%) and 42 days (46% versus 29%), respectively (p<.05). In a cell culture model, rough surface topography positively modulates collagen biosynthesis and accumulation and the expression of genes associated with collagen cross-linking in adherent hMSC. The altered biosynthesis of the collagen-rich ECM adjacent to endosseous implants may influence the biomechanical properties of osseointegrated endosseous implants.

Long-term bond strengths to dentin treated with different re-wetting solutions.

PURPOSE: To evaluate the microtensile bond strengths (microTBS) of two etch-and-rinse one-bottle adhesive systems to air-dried dentin re-wet with different agents. METHODS: 48 bovine teeth were ground flat to 600-grit and were assigned for treatment with either Single Bond or One-Step adhesives. Each group had three subgroups of re-wetting agents: water, Gluma Desensitizer and Aqua-Prep F. The teeth were acid-etched, air-dried for 5 seconds and re-wet with water, Gluma Desensitizer or Aqua-Prep F for 30 seconds and blot dried. Control specimens were prepared using a moist bonding technique. The adhesives were applied and the teeth were restored with Filtek Z250 or Renew composite. After 24 hours in distilled water at 37 degrees C, the teeth were sectioned into 0.7 mm-thick slabs, trimmed, and immediately tested for microTBS or stored for 6 months or 1 year prior to testing. Fracture sites were examined under scanning electron microscope (SEM). Data were evaluated by one- and three-way ANOVA, and Fisher's PLSD test (P<0.05). RESULTS: Except for Aqua-Prep F, the microTBS in the control, water and Gluma Desensitizer subgroups did not change significantly after 1-year for both Single Bond and One-Step groups. SEM analysis showed no specific pattern of fracture in the Single Bond specimens. One-Step had the majority of the fractures at the interface at baseline, and becoming a mixture of fractures at the interface and within the adhesive resin after 1 year.

Bond strengths of a 1-step self-etching system to caries-affected and normal dentin.

This study was designed to evaluate the bond strengths of a 1-step self-etching system and a 2-step "etch and rinse" adhesive system to caries-affected dentin and normal dentin. In addition, the micromorphology of the adhesive interfaces was analyzed using scanning electron microscopy (SEM). Extracted human molars with occlusal caries that had been stored frozen were ground in order to expose the caries-affected dentin and surrounding normal dentin. The teeth were then bonded using either Adper Prompt L-Pop or Single Bond (3M ESPE) and restored with Filtek Z250 (3MESPE). After storage in water for 24 hours at 37 degrees C, the teeth were sectioned, prepared for microtensile bond strength test and tested in tension at a crosshead speed of 1-mm/minute. After debonding of the interfaces, microhardness of the dentin underlying the interface of all specimens was measured. The thickness of the hybrid layers was observed under SEM. The results of this study indicate that the bond strength of Adper Prompt L-Pop adhesive was significantly higher to normal dentin than to caries-affected dentin (p<0.05) and that the bond strength of Single Bond to both normal and caries-affected dentin was not significantly different (p>0.05). Additionally, the thickness of the hybrid layers produced by both adhesive systems was thicker for caries-affected dentin.

Microtensile bond strength of luting materials to coronal and root dentin.

PURPOSE: The purpose of this study was to evaluate the microtensile bond strength (muTBS) of two dual-cured resin cements and a glass ionomer cement to coronal dentin versus root dentin. MATERIALS AND METHODS: RelyX Unicem (3M ESPE, St. Paul, MN, USA) and Panavia F (Kuraray Medical Inc., Tokyo, Japan) were the resin cements used and FujiCEM (GC Corp., Tokyo, Japan) was the glass ionomer cement used. Once separated, the labial coronal and root surfaces of six bovine incisors were ground with 600-grit SiC papers to expose middle dentin. Then, the dentin surfaces were treated following the manufacturers' instructions and a 1 mm thick layer of each material was applied to the flattened coronal and root surfaces. Each material was cured following the manufacturers' recommendations and a composite buildup was made over the cured luting materials for testing purposes. After 24 hours in water at 37 degrees C, the teeth were sectioned into 1 mm x 1 mm x 6 mm beams and tested for muTBS. The data were analyzed by one- and two-way analysis of variance and Fisher's Protected Least Squares Differences test (p < .05). RESULTS: The microTBSs to coronal and root dentin were similar within each cement. Comparing the materials, RelyX Unicem presented the highest muTBS, followed by Panavia F and FujiCEM, respectively (p < .0001). CONCLUSIONS: Although there were differences in muTBS among the materials tested, no significant differences were found between bond strengths to coronal and root substrates. CLINICAL SIGNIFICANCE: Since bond strengths of luting materials to coronal and root dentin showed comparable results, there is no need to treat those surfaces differently prior to luting of indirect restorations. Nevertheless, because significant differences existed among the different luting materials, the choice of a luting material should be based on the type of preparation and restoration as well as the need for fluoride release.