Fibrocyte: A missing piece in the pathogenesis of fibrous epulis.

OBJECTIVES: To explore the role of fibrocytes in the recurrence and calcification of fibrous epulides. METHODS: Different subtypes of fibrous epulides and normal gingival tissue specimens were first collected for histological and immunofluorescence analyses to see if fibrocytes were present and whether they differentiated into myofibroblasts and osteoblasts upon stimulated by transforming growth factor-ß1 (TGF-ß1). Electron microscopy and elemental analysis were used to characterize the extracellular microenvironment in different subtypes of fibrous epulides. Human peripheral blood mononuclear cells (PBMCs) were subsequently isolated from in vitro models to mimic the microenvironment in fibrous epulides to identify whether TGF-ß1 as well as the calcium and phosphorus ion concentration in the extracellular matrix (ECM) of a fibrous epulis trigger fibrocyte differentiation. RESULTS: Fibrous epulides contain fibrocytes that accumulate in the local inflammatory environment and have the ability to differentiate into myofibroblasts or osteoblasts. TGF-ß1 promotes fibrocytes differentiation into myofibroblasts in a concentration-dependent manner, while TGF-ß1 stimulates the fibrocytes to differentiate into osteoblasts when combined with a high calcium and phosphorus environment. CONCLUSIONS: Our study revealed fibrocytes play an important role in the fibrogenesis and osteogenesis in fibrous epulis, and might serve as a therapeutic target for the inhibition of recurrence of fibrous epulides.

A feasible method to eliminate nanoleakage in dentin hybrid layers.

PURPOSE: To determine whether high-pressure air blowing during adhesive application affects the infiltration of resin comonomers and nanoleakage manifestation in the resin/dentin interface under simulated pulpal pressure. MATERIALS AND METHODS: Thirty mid-coronal dentin surfaces were bonded with an etch-and-rinse adhesive (Adper Single Bond 2) under simulated pulpal pressure. In the control group, the adhesive was thinned by ordinary air blowing with a pressure of 0.2 MPa, while in the experimental group, a high-pressure air blowing technique (pressure: 0.4 MPa) was used. All other procedures followed the manufacturer's instructions. Resin tag formation and nanoleakage in the bonding interface were evaluated with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: When adhesive was thinned with high pressure air blowing, longer and more homogeneous resin tags were formed. The bonding interface demonstrated good overall morphology and integrity. Almost perfect infiltration of resin and no obvious nanoleakage were observed. CONCLUSION: Thinning of adhesive with high-pressure air blowing provides a clinically feasible adjunctive procedure for better resin infiltration.

Recent advances in the pathogenesis and prevention strategies of dental calculus.

Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

Biomimetic Self-Maturation Mineralization System for Enamel Repair.

Enamel repair is crucial for restoring tooth function and halting dental caries. However, contemporary research often overlooks the retention of organic residues within the repair layer, which hinders the growth of dense crystals and compromises the properties of the repaired enamel. During the maturation of natural enamel, the organic matrix undergoes enzymatic processing to facilitate further crystal growth, resulting in a highly mineralized tissue. Inspired by this process, a biomimetic self-maturation mineralization system is developed, comprising ribonucleic acid-stabilized amorphous calcium phosphate (RNA-ACP) and ribonuclease (RNase). The RNA-ACP induces initial mineralization in the form of epitaxial crystal growth, while the RNase present in saliva automatically triggers a biomimetic self-maturation process. The mechanistic study further indicates that RNA degradation prompts conformational rearrangement of the RNA-ACP, effectively excluding the organic matter introduced earlier. This exclusion process promotes lateral crystal growth, resulting in the generation of denser enamel-like apatite crystals that are devoid of organic residues. This strategy of eliminating organic residues from enamel crystals enhances the mechanical and physiochemical properties of the repaired enamel. The present study introduces a conceptual biomimetic mineralization strategy for effective enamel repair in clinical practice and offers potential insights into the mechanisms of biomineral formation.

Intrafibrillar silicification of collagen scaffolds for sustained release of stem cell homing chemokine in hard tissue regeneration.

Traditional bone regeneration strategies relied on supplementation of biomaterials constructs with stem or progenitor cells or growth factors. By contrast, cell homing strategies employ chemokines to mobilize stem or progenitor cells from host bone marrow and tissue niches to injured sites. Although silica-based biomaterials exhibit osteogenic and angiogenic potentials, they lack cell homing capability. Stromal cell-derived factor-1 (SDF-1) plays a pivotal role in mobilization and homing of stem cells to injured tissues. In this work, we demonstrated that 3-dimensional collagen scaffolds infiltrated with intrafibrillar silica are biodegradable and highly biocompatible. They exhibit improved compressive stress-strain responses and toughness over nonsilicified collagen scaffolds. They are osteoconductive and up-regulate expressions of osteogenesis- and angiogenesis-related genes more significantly than nonsilicified collagen scaffolds. In addition, these scaffolds reversibly bind SDF-1α for sustained release of this chemokine, which exhibits in vitro cell homing characteristics. When implanted subcutaneously in an in vivo mouse model, SDF-1α-loaded silicified collagen scaffolds stimulate the formation of ectopic bone and blood capillaries within the scaffold and abrogate the need for cell seeding or supplementation of osteogenic and angiogenic growth factors. Intrafibrillar-silicified collagen scaffolds with sustained SDF-1α release represent a less costly and complex alternative to contemporary cell seeding approaches and provide new therapeutic options for in situ hard tissue regeneration.

The integration of peri-implant soft tissues around zirconia abutments: Challenges and strategies.

Stable soft tissue integration around the implant abutment attenuates pathogen penetration, protects underlying bone tissue, prevents peri-implantitis and is essential in maintaining long-term implant stability. The desire for "metal free" and "aesthetic restoration" has favored zirconia over titanium abutments, especially for implant restorations in the anterior region and for patients with thin gingival biotype. Soft tissue attachment to the zirconia abutment surface remains a challenge. A comprehensive review of advances in zirconia surface treatment (micro-design) and structural design (macro-design) affecting soft tissue attachment is presented and strategies and research directions are discussed. Soft tissue models for abutment research are described. Guidelines for development of zirconia abutment surfaces that promote soft tissue integration and evidence-based references to inform clinical choice of abutment structure and postoperative maintenance are presented.

Novel Digital Mouth Preparation Technique for Fabricating Implant-Retained Removable Partial Dentures with Distal Extension: a Case Report.

Implant-retained removable partial dentures (RPDs) are commonly used to resolve the complications associated with traditional distal extension RPDs; however, this technology does not consider the necessity and importance of parallelism between the path of RPD insertion and the long axis of the implant. This clinical report presents a novel digital preparation technique that involves the preparation of parallel guiding planes on abutment teeth and implant insertion in the distal extension area using a computer-aided design and manufacturing template. This clinical case of implant-retained RPDs illustrates the fabrication and application of the digital template. Using this technique, the path of RPD insertion is parallel to the long axis of the implant. As a result, the components of the implant-retained RPD, including the abutment teeth, implants and attachments, can demonstrate greater longevity.

Advances in materials-based therapeutic strategies against osteoporosis.

Osteoporosis is caused by the disruption in homeostasis between bone formation and bone resorption. Conventional management of osteoporosis involves systematic drug administration and hormonal therapy. These treatment strategies have limited curative efficacy and multiple adverse effects. Biomaterials-based therapeutic strategies have recently emerged as promising alternatives for the treatment of osteoporosis. The present review summarizes the current status of biomaterials designed for managing osteoporosis. The advantages of biomaterials-based strategies over conventional systematic drug treatment are presented. Different anti-osteoporotic delivery systems are concisely addressed. These materials include injectable hydrogels and nanoparticles, as well as anti-osteoporotic bone tissue engineering materials. Fabrication techniques such as 3D printing, electrostatic spinning and artificial intelligence are appraised in the context of how the use of these adjunctive techniques may improve treatment efficacy. The limitations of existing biomaterials are critically analyzed, together with deliberation of the future directions in biomaterials-based therapies. The latter include discussion on the use of combination strategies to enhance therapeutic efficacy in the osteoporosis niche.

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES.

BACKGROUND: Although tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown. METHODS: Data were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association. RESULTS: The association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (ß=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food. CONCLUSIONS: The association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.

The immunomodulatory effects of RNA-based biomaterials on bone regeneration.

The use of RNA as therapeutic agents is a visionary idea in contemporary medicine. Some forms of RNA can modulate the immune response of the host to enhance tissue regeneration events such as osteogenesis. Herein, RNA molecules commercially available for immunomodulatory applications (imRNA) were used to prepare biomaterials for bone regeneration. The polyanionic imRNA stabilized calcium phosphate ionic clusters to produce imRNA-ACP that had the capacity to mineralize the intrafibrillar compartments of collagen fibrils. For the first time, it was shown that incorporating imRNA-ACP into collagen scaffolds resulted in rapid new bone formation in cranial defects of mice. Both in vivo and in vitro results demonstrated that macrophage polarization was highly-sensitive to the imRNA-ACP containing collagen scaffolds. Macrophages were polarized into the anti-inflammatory M2 phenotype that produced anti-inflammation cytokines and growth factors. The favorable osteoimmunological microenvironment created by the scaffolds prevented their immunorejection and facilitated osteogenesis. The potential of RNA in creating immunomodulatory biomaterials has been underestimated in the past. The overall aim of this study was to explore the potential application of imRNA-based biomaterials in bone tissue engineering, with the competitive edge of facile synthesis and excellent biocompatibility. STATEMENT OF SIGNIFICANCE: In this work, commercially available RNA extracted from bovine spleens for immunomodulatory applications (imRNA) were used to stabilize amorphous calcium phosphate (ACP) and induce mineralization within collagen fibrils. Incorporation of imRNA-ACP into collagen scaffolds regenerated new bone in-situ. Because of its immunomodulatory effects, the imRNA-ACP that was incorporated into collagen scaffolds modulated the local immune environment of murine cranial defects by altering the macrophage phenotype through JAK2/STAT3 signaling pathway. The novelty of this work existed in the discovery of RNA's potential in creating immunomodulatory biomaterials. With the competitive edge of facile synthesis and excellent biocompatibility, the imRNA-based biomaterials are potentially useful for future bone tissue engineering applications.

Manifestation and Mechanisms of Abnormal Mineralization in Teeth.

Tooth biomineralization is a dynamic and complicated process influenced by local and systemic factors. Abnormal mineralization in teeth occurs when factors related to physiologic mineralization are altered during tooth formation and after tooth maturation, resulting in microscopic and macroscopic manifestations. The present Review provides timely information on the mechanisms and structural alterations of different forms of pathological tooth mineralization. A comprehensive study of these alterations benefits diagnosis and biomimetic treatment of abnormal mineralization in patients.

A biomaterial-based therapy using a sodium hyaluronate/bioglass composite hydrogel for the treatment of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant oral disorder. Its pathophysiology is extremely complex, including excessive collagen deposition, massive inflammatory infiltration, and capillary atrophy. However, the existing clinical treatment methods do not fully take into account all the pathophysiological processes of OSF, so they are generally low effective and have many side effects. In the present study, we developed an injectable sodium hyaluronate/45S5 bioglass composite hydrogel (BG/HA), which significantly relieved mucosal pallor and restricted mouth opening in OSF rats without any obvious side effects. The core mechanism of BG/HA in the treatment of OSF is the release of biologically active silicate ions, which inhibit collagen deposition and inflammation, and promote angiogenesis and epithelial regeneration. Most interestingly, silicate ions can overall regulate the physiological environment of OSF by down-regulating α-smooth muscle actin (α-SMA) and CD68 and up-regulating CD31 expression, as well as regulating the expression of pro-fibrotic factors [transforming growth factor-ß1 (TGF-ß1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and tissue inhibitors of metalloproteinase-1 (TIMP-1)] and anti-fibrotic factors [interleukin-1ß (IL-1ß)] in macrophage. In conclusion, our study shows that BG/HA has great potential in the clinical treatment of OSF, which provides an important theoretical basis for the subsequent development of new anti-fibrotic clinical preparations. STATEMENT OF SIGNIFICANCE: : Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant mucosal disease with significant impact on the quality of patients' life. However, the existing clinical treatments have limited efficacy and many side effects. There is an urgent need for development of specific drugs for OSF treatment. In the present study, bioglass (BG) composited with sodium hyaluronate solution (HA) was used to treat OSF in an arecoline-induced rat model. BG/HA can significantly inhibit collagen deposition, regulate inflammatory response, promote angiogenesis and repair damaged mucosal epithelial cells, and thereby mitigate the development of fibrosis in vivo.

Evaluation of a novel primer containing isocyanate group on dentin bonding durability.

OBJECTIVES: To evaluate the benefits of a novel dentin-bonding primer, namely, isocyanate-terminated urethane methacrylate precursor (UMP), which can form covalent bonds with demineralized dentin collagen. METHODS: The synthesized and purified UMP monomer was characterized and tested its effects on the degree of conversion (DC) and wettability of an acetone-based dental adhesive. Then UMP primers of different concentrations were formulated and used to prepare adhesive specimens, which were compared with solvent-treated groups. Primer-treated specimens with and without aging were also compared. To evaluate the bonding interface, microtensile strength tests, nano-indentation tests and nanoleakage- eavaluation were performed using a field-emission scanning electron microscope and nano-indenter. Data were analyzed using SPSS 20.0 software with significance set at α = 0.05 using one-way analysis of variance (ANOVA) and two-way ANOVA to characterize the effects of the primer. RESULTS: Treatment with the UMP primer promoted the DC and wettability of the adhesive on the demineralized dentin surface (P < 0.05); it also increased the bond strength of the aged dentin bonding interface (P < 0.05). Nanoleakage was reduced; the bonding interface became more stable, and the continuity and strength of the hybrid layer improved (P < 0.05) following UMP treatment. The application of 5 mM UMP as a primer for dentin bonding could lead to a stable bonding interface and long-lasting bonding effects. SIGNIFICANCE: The use of 5 mM UMP primer developed in this study could improve dentin bonding durability and has excellent clinical application prospects.

Polyetheretherketone Framework for Implant-supported Full-arch Fixed Dental Prostheses in a Periodontitis Patient with a 6-year Follow-up: a Case Report.

Dental implants are widely used in the rehabilitation of patients with edentulous jaws caused by periodontitis. The success of implants is closely related to their framework material and patients' periodontal health. Polyetheretherketone (PEEK) is a kind of high polymer material that has broad prospects as the framework for full-arch dental prostheses, but long-term follow-up data are lacking. The present clinical report demonstrates the use of a PEEK framework for the construction of an implant-supported full-arch fixed dental prosthesis for a patient diagnosed with periodontitis. With the guidance of biological width, a provisional retained restoration was achieved to create the emergence profile, resulting in a 3D printed PEEK framework with good aesthetics and biological functions.

Multiple Cervical Root Resorption Involving 22 Teeth: A Case with Potential Genetic Predisposition.

A rare case of extensive multiple idiopathic cervical root resorption with potential genetic predisposition was presented. A heathy 19-year-old Chinese male with no contributory medical or family/social history complained of pain during mastication that lasted for several months. Oral examination identified 7 missing teeth and external cervical root resorption involving 9 teeth. Comparison of orthopantomograms taken in May 2021 and February 2022 identified that cervical root resorption occurred in 22 teeth. Resorption commenced at the cementoenamel junction and progressed rapidly over the 9-month period. Laboratory test results were within normal limits. Trio-based whole-exome sequencing showed a missense mutation c.5630 C > T in the filamin A (FLNA) gene at chromosome X of the subject. This is suggestive of the possibility of sex-linked recessive inheritance. This is the first study to report FLNA mutation in human subjects with cervical root resorption involving multiple teeth.

Regulation of biomineralization by proteoglycans: From mechanisms to application.

Proteoglycans consist of core proteins and one or more covalently-linked glycosaminoglycan chains. They are structurally complex and heterogeneous. Proteoglycans bind to cell surface receptors, cytokines, growth factors and have strong affinity for collagen fibrils. Together with their complex spatial structures and different charge densities, proteoglycans are directly or indirectly involved in biomineralization. The present review focused on the potential mechanisms of proteoglycans-mediated biomineralization. Topics covered include the ability of proteoglycans to influence the proliferation and differentiation of odontoblasts and osteoblasts through complex signaling pathways, as well as regulate the aggregation of collagen fibrils and mineral deposition. The functions of proteoglycans in mineralization regulation and biomimetic properties render them important components in bone tissue engineering. Hence, the integrated impact of proteoglycans on bone formation was also succinctly deliberated. The potential of proteoglycans to function therapeutic targets for relieving the symptoms of ectopic mineralization and mineralization defects was also comprehensively addressed.

A mussel glue-inspired monomer-etchant cocktail for improving dentine bonding.

OBJECTIVES: The humid oral environment adversely affects the interaction between a functionalised primer and dentine collagen after acid-etching. Robust adhesion of marine mussels to their wet substrates instigates the quest for a strategy that improves the longevity of resin-dentine bonds. In the present study, an etching strategy based on the incorporation of biomimetic dopamine methacrylamide (DMA) as a functionalised primer into phosphoric acid etchant was developed. The mechanism and effect of this DMA-containing acid-etching strategy on bond durability were examined. METHODS: Etchants with different concentrations of DMA (1, 3 or 5 mM) were formulated and tested for their demineralisation efficacy. The interaction between DMA and dentine collagen, the effect of DMA on collagen stability and the collagenase inhibition capacity of the DMA-containing etchants were evaluated. The effectiveness of this new etching strategy on resin-dentine bond durability was investigated. RESULTS: All etchants were capable of demineralising dentine and exposing the collagen matrix. The latter strongly integrated with DMA via covalent bond, hydrogen bond and Van der Waals' forces. These interactions significantly improve collagen stability and inhibited collagenase activity. Application of the etchant containing 5 mM DMA achieved the most durable bonding interface. CONCLUSION: Dopamine methacrylamide interacts with dentine collagen in a humid environment and improves collagen stability. The monomer effectively inactivates collagenase activity. Acid-etching with 5 mM DMA-containing phosphoric acid has the potential to prolong the longevity of bonded dental restorations without compromising clinical operation time. CLINICAL SIGNIFICANCE: The use of 5 mM dopamine methacrylamide-containing phosphoric acid for etching dentine does not require an additional clinical step and has potential to improve the adhesive performance of bonded dental restorations.

Polyphosphate-crosslinked collagen scaffolds for hemostasis and alveolar bone regeneration after tooth extraction.

Post-extraction bleeding and alveolar bone resorption are the two frequently encountered complications after tooth extraction that result in poor healing and rehabilitation difficulties. The present study covalently bonded polyphosphate onto a collagen scaffold (P-CS) by crosslinking. The P-CS demonstrated improved hemostatic property in a healthy rat model and an anticoagulant-treated rat model. This improvement is attributed to the increase in hydrophilicity, increased thrombin generation, platelet activation and stimulation of the intrinsic coagulation pathway. In addition, the P-CS promoted the in-situ bone regeneration and alveolar ridge preservation in a rat alveolar bone defect model. The promotion is attributed to enhanced osteogenic differentiation of bone marrow stromal cells. Osteogenesis was improved by both polyphosphate and blood clots. Taken together, P-CS possesses favorable hemostasis and alveolar ridge preservation capability. It may be used as an effective treatment option for post-extraction bleeding and alveolar bone loss. Statement of significance: Collagen scaffold is commonly used for the treatment of post-extraction bleeding and alveolar bone loss after tooth extraction. However, its application is hampered by insufficient hemostatic and osteoinductive property. Crosslinking polyphosphate with collagen produces a modified collagen scaffold that possesses improved hemostatic performance and augmented bone regeneration potential.

Development of an Antibacterial Dentin Adhesive.

Nisin is a peptide that possesses potent antibacterial properties. This study evaluated the antibacterial activity of a nisin-doped adhesive against Streptococcus mutans, as well as its degree of conversion and microtensile bond strength (µTBS) to dentin. Nisin was added to the adhesive Adper Single Bond 2 (3M ESPE), resulting in four groups: Control Group (Single Bond 2); Group 1% (1 wt% nisin-incorporated), Group 3% (3 wt% nisin-incorporated) and Group 5% (5 wt% nisin-incorporated). Antibacterial activity against S. mutans was evaluated using colony-forming unit counts (CFU). The degree of conversion was tested using FTIR. Forty human teeth were restored for µTBS evaluation. Data were statistically analyzed with ANOVA and Tukey tests at α = 0.05. The nisin-doped adhesives, for all concentrations, exhibited a significant inhibition of the growth of S. mutans (p < 0.05); Incorporation of 5% and 3% nisin decreased the degree of conversion of the adhesive (p < 0.05). The µTBS (in MPa): Control Group­38.3 ± 2.3A, Group 1%­35.6 ± 2.1A, Group 3%­27.1 ± 1.6B and Group 5%­22.3 ± 1.0C. Nisin-doped adhesives exerted a bactericidal effect on S. mutans. The µTBS and degree of conversion of adhesive were not affected after incorporation of 1% nisin.