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.

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.

Research Progress of Duodenal-Jejunal Bypass Liner in the Treatment of Obesity and Type 2 Diabetes Mellitus.

With the development of economy and improvement of people's living standards, the incidence of obesity and type 2 diabetes mellitus (T2DM) has increased significantly and obesity has also become one of the most important risk factors of T2DM. In light of these trends, there have been many ways to take effect in losing weight. However, they also have corresponding deficiencies including inapparent curative effect, complex and incomplete reversible procedures and severe complications. Duodenal-Jejunal Bypass Liner (DJBL), which mimics Roux-en-Y gastric bypass (RYGB), is proved to play a key role in weight loss and control of T2DM. DJBL is reversible, less invasive and is more suitable for the treatment of obesity and T2DM, which is associated with multiple mechanisms, including incretin effect, gastric emptying mechanism, bile acid regulation, intestinal microbiota, inflammatory reaction mechanism and neural mechanism. In our review, we aimed to elaborate DJBL's clinical efficacy, safety and mechanisms in detail.

Color change of glass ceramic restorations cemented by four types of dual-cured resin luting agents with different initiator systems.

This study aimed to comprehensively evaluate the effect of dual-cured resin luting agents with different initiator systems on the color stability of glass ceramic restorations by simulating various clinical glass ceramic restorations. Three commonly used shades from each of the two dual-cured resin luting agents with an amine-initiation system or without it were studied. The individual specimens had different translucency and thickness and were artificially aged using a xenon light aging machine. The color was measured before and after aging using a digital spectrophotometer with the difference calculated and analyzed statistically. As results, the amine-free dual-cured resin luting agents were more color stable than those using amine-initiation systems for both uncovered and bonding groups. The translucency and thickness of the ceramic, and shade and type of the resin luting agent significantly affected the color stability of glass ceramic restorations.

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.

Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism.

Background: Globally, obesity is a significant public problem, especially when aging. Sesamol, a phenolic lignan present in sesame seeds, might have a positive effect on high-fat diet (HFD)-induced obesity associated with aging. Objective: The purpose of current research study was to explore salutary effects and mechanisms of sesamol in treating alimentary obesity and associated metabolic syndrome in middle-aged mice. Methods: C57BL/6J mice aged 4-6 weeks and 6-8 months were assigned to the young normal diet group, middle-aged normal diet group, middle-aged HFD group, and middle-aged HFD + sesamol group. At the end of experiment, glucose tolerance test and insulin tolerance test were performed; the levels of lipids and oxidative stress-related factors in the serum and skeletal muscle were detected using chemistry reagent kits; lipid accumulation in skeletal muscle was observed by oil red O staining; the expressions of muscular glucose and lipid metabolism associated proteins were measured by Western blotting. Results: Sesamol decreased the body weight and alleviated obesity-associated metabolism syndrome in middle-aged mice, such as glucose intolerance, insulin resistance, dyslipidemia, and oxidative stress. Moreover, muscular metabolic disorders were attenuated after treatment with sesamol. It increased the expression of glucose transporter type-4 and down-regulated the protein levels of pyruvate dehydrogenase kinase isozyme 4, implying the increase of glucose uptake and oxidation. Meanwhile, sesamol decreased the expression of sterol regulatory element binding protein 1c and up-regulated the phosphorylation of hormone-sensitive lipase and the level of carnitine palmityl transferase 1α, which led to the declined lipogenesis and the increased lipolysis and lipid oxidation. In addition, the SIRT1/AMPK signaling pathway was triggered by sesamol, from which it is understood how sesamol enhances glucose and lipid metabolism. Conclusions: Sesamol counteracts on metabolic disorders of middle-aged alimentary obese mice through regulating skeletal muscle glucose and lipid metabolism, which might be associated with the stimulation of the SIRT1/AMPK pathway.

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.

Multifunctional Nanomachinery for Enhancement of Bone Healing.

The visionary idea that RNA adopts nonbiological roles in today's nanomaterial world has been nothing short of phenomenal. These RNA molecules have ample chemical functionality and self-assemble to form distinct nanostructures in response to external stimuli. They may be combined with inorganic materials to produce nanomachines that carry cargo to a target site in a controlled manner and respond dynamically to environmental changes. Comparable to biological cells, programmed RNA nanomachines have the potential to replicate bone healing in vitro. Here, an RNA-biomineral nanomachine is developed, which accomplishes intrafibrillar and extrafibrillar mineralization of collagen scaffolds to mimic bone formation in vitro. Molecular dynamics simulation indicates that noncovalent hydrogen bonding provides the energy source that initiates self-assembly of these nanomachines. Incorporation of the RNA-biomineral nanomachines into collagen scaffolds in vivo creates an osteoinductive microenvironment within a bone defect that is conducive to rapid biomineralization and osteogenesis. Addition of RNA-degrading enzymes into RNA-biomineral nanomachines further creates a stop signal that inhibits unwarranted bone formation in tissues. The potential of RNA in building functional nanostructures has been underestimated in the past. The concept of RNA-biomineral nanomachines participating in physiological processes may transform the nanoscopic world of life science.

Use of a digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery.

A digitally guided triple technique for bone reduction, implant placement, and immediate interim prostheses in complete-arch implant surgery is presented. This technique integrates bone reduction and implant placement information into a dual-function surgical template and introduces a digital approach to fabricating immediate interim implant-supported fixed dental prostheses with the same occlusal relationship as the one evaluated with diagnostic removable prostheses.

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.

Polyetheretherketone versus titanium CAD-CAM framework for implant-supported fixed complete dentures: a retrospective study with up to 5-year follow-up.

PURPOSE: To evaluate the performance of polyetheretherketone (PEEK) versus titanium computer-aided designed and manufactured (CAD-CAM) framework for implant-supported fixed complete dentures (ISFCDs) with a follow-up for a duration of up to 5 years. METHODS: Consecutively edentulous patients who underwent ISFCDs with a PEEK framework or titanium framework at one dental specialist center were included in this retrospective study. Implant/prosthesis survival rates, mechanical/biological complications, and bone and soft tissue parameters were analyzed. Overall survival was analyzed using Kaplan-Meier survival curves and the log-rank test. RESULTS: Sixty ISFCDs (29 PEEK, 31 titanium) performed on 43 edentulous patients (331 implants) were included. An implant survival rate of 100% was obtained. There was no significant difference in the cumulative prosthesis survival rate between the PEEK (93.1%) and titanium groups (93.5%). The most common mechanical complications were fracture of the artificial veneer in both the PEEK (13.8%) and titanium (16.7%) groups. Bruxers had a higher prevalence of mechanical complications than non-bruxers (p<0.05). The biological complications included bleeding upon probing (13.8% for the PEEK group; 16.1% for the titanium group), soft tissue inflammation (3.4% for the PEEK group; 3.2% for the titanium group), and temporomandibular disorders (6.5% for the titanium group). The vertical bone loss was significantly lower in the PEEK group (0.70 mm) than in the titanium group (0.96 mm). Smokers had a significantly higher prevalence of biological complications than non-smokers. CONCLUSION: Within the limitations of this study, ISFCDs with PEEK frameworks can provide good prognosis for edentulous patients, still requiring longer-term validation.

Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization.

Although deoxyribonucleic acid (DNA) is the genetic coding for the very essence of life, these macromolecules or components thereof are not necessarily lost after a cell dies. There appears to be a link between extracellular DNA and biomineralization. Here the authors demonstrate that extracellular DNA functions as an initiator of collagen intrafibrillar mineralization. This is confirmed with in vitro and in vivo biological mineralization models. Because of their polyanionic property, extracellular DNA molecules are capable of stabilizing supersaturated calcium phosphate solution and mineralizing 2D and 3D collagen matrices completely as early as 24 h. The effectiveness of extracellular DNA in biomineralization of collagen is attributed to the relatively stable formation of amorphous liquid droplets triggered by attraction of DNA to the collagen fibrils via hydrogen bonding. These findings suggest that extracellular DNA is biomimetically significant for fabricating inorganic-organic hybrid materials for tissue engineering. DNA-induced collagen intrafibrillar mineralization provides a clue to the pathogenesis of ectopic mineralization in different body tissues. The use of DNase for targeting extracellular DNA at destined tissue sites provides a potential solution for treatment of diseases associated with ectopic mineralization.

Upregulation of mitochondrial dynamics is responsible for osteogenic differentiation of mesenchymal stem cells cultured on self-mineralized collagen membranes.

Collagen membranes crosslinked with high molecular weight polyacrylic acid (HPAA) are capable of self-mineralization via in situ intrafibrillar mineralization. These HPAA-crosslinked collagen membranes (HCM) have been shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs) and enhance bone regeneration in vivo. Nevertheless, the biological triggers involved in those processes and the associated mechanisms are not known. Here, we identified the contribution of mitochondrial dynamics in HCM-mediated osteogenic differentiation of MSCs. Mitochondriogenesis markers were significantly upregulated when MSCs were cultured on HCM, committing the MSCs to osteogenic differentiation. The mitochondria fused to form an interconnected mitochondrial network in response to the high energy requirements. Mitochondrial fission in MSCs was also triggered by HCM; fission slightly declined at 14 days to restore the equilibrium in mitochondrial dynamics. Mitophagy, another event that regulates mitochondrial dynamics, occurred actively to remove dysfunctioned mitochondria and isolate damaged mitochondria from the rest of network. The mitophagy level of MSCs was significantly elevated in the presence of HCM. Taken together, the present findings indicate that upregulation of mitochondrial dynamics via mitochondriogenesis, fusion, fission and mitophagy is responsible for HCM-mediated osteogenic differentiation of MSCs. STATEMENT OF SIGNIFICANCE: High molecular weight polyacrylic acid (HPAA)-crosslinked collagen membrane (HCM) was found to promote in-situ bone regeneration because of it can stimulate osteogenic differentiation of mesenchymal stem cells (MSCs). Nevertheless, the biological triggers involved in those processes and associated mechanisms are not known. This study identifies that activation of mitochondrial dynamics is centrally involved in HCM-mediated osteogenic differentiation of MSCs. The HCM accelerates mitochondriogenesis and regulates homeostasis of the mitochondrial network in response to the increased energy demand for osteogenic differentiation. Concomitantly, mitophagy actively occurs to remove dysfunctioned mitochondria from the rest of the mitochondrial network. Identification of the involvement of mitophagy in HCM-mediated osteogenic differentiation of MSCs opens new vistas in the application of biomimetic mineralization in bone tissue regeneration.

ß-Caryophyllene Ameliorates MSU-Induced Gouty Arthritis and Inflammation Through Inhibiting NLRP3 and NF-κB Signal Pathway: In Silico and In Vivo.

Gouty arthritis serves as an acute reaction initiated by the deposition of monosodium urate (MSU) crystals around the joints. In this study, the anti-inflammatory effects of phytochemical ß-caryophyllene on MSU crystal-induced acute gouty arthritis in vivo and in silico were explored. Through bioinformatics methods and molecular docking, it screened the specific influence pathway of ß-caryophyllene on gout. Certain methods including enzyme-linked immunosorbent assay, western blotting, and immunohistochemical staining were adopted to quantify. ß-caryophyllene significantly reduced inflammation and function of ankle joints in MSU Crystals-induced gouty arthritis rats, while decreasing serum cytokine levels. Furthermore, it inhibited the expressions of NLRP3, Caspase-1, ASC, TLR4, MyD88, p65, and IL-1ß in the synovial tissue so as to reduce inflammation and protect ankle joints' function. A new research approach in which ß-caryophyllene treatment to acute attacks of gout is provided through the research results.

Biomaterials from the sea: Future building blocks for biomedical applications.

Marine resources have tremendous potential for developing high-value biomaterials. The last decade has seen an increasing number of biomaterials that originate from marine organisms. This field is rapidly evolving. Marine biomaterials experience several periods of discovery and development ranging from coralline bone graft to polysaccharide-based biomaterials. The latter are represented by chitin and chitosan, marine-derived collagen, and composites of different organisms of marine origin. The diversity of marine natural products, their properties and applications are discussed thoroughly in the present review. These materials are easily available and possess excellent biocompatibility, biodegradability and potent bioactive characteristics. Important applications of marine biomaterials include medical applications, antimicrobial agents, drug delivery agents, anticoagulants, rehabilitation of diseases such as cardiovascular diseases, bone diseases and diabetes, as well as comestible, cosmetic and industrial applications.

Crosstalk between Bone and Nerves within Bone.

For the past two decades, the function of intrabony nerves on bone has been a subject of intense research, while the function of bone on intrabony nerves is still hidden in the corner. In the present review, the possible crosstalk between bone and intrabony peripheral nerves will be comprehensively analyzed. Peripheral nerves participate in bone development and repair via a host of signals generated through the secretion of neurotransmitters, neuropeptides, axon guidance factors and neurotrophins, with additional contribution from nerve-resident cells. In return, bone contributes to this microenvironmental rendezvous by housing the nerves within its internal milieu to provide mechanical support and a protective shelf. A large ensemble of chemical, mechanical, and electrical cues works in harmony with bone marrow stromal cells in the regulation of intrabony nerves. The crosstalk between bone and nerves is not limited to the physiological state, but also involved in various bone diseases including osteoporosis, osteoarthritis, heterotopic ossification, psychological stress-related bone abnormalities, and bone related tumors. This crosstalk may be harnessed in the design of tissue engineering scaffolds for repair of bone defects or be targeted for treatment of diseases related to bone and peripheral nerves.

[Application of biomimetic restoration in oral-maxillofacial hard tissue repair].

Oral-maxillofacial hard tissue is the support of maxillofacial structure and appearance, and lays the foundation for functions of oral and maxillofacial system. Once the defect occurs, it will not only affect the physiological functions such as chewing and pronunciation, but also have a significant impact on the psychological and social life of patients. However, the self-repairing capability of the oral-maxillofacial hard tissue is pretty limited, in which case, substitute materials are required for tissue repair. A huge gap exists between the physical, chemical, structural characteristics of conventional substitute materials and those of human hard tissues, resulting in poor repair effect. Based on this, scholars simulated the process of biomineralization in the development of hard tissues, to improve the structure and function of materials through biomimetic mineralization technology and enhance the repair performance of materials. The current understanding of biomineralization theory and the construction of biomimetic repair technology is still in the stage of rapid development. In recent years, a mass of innovative studies are keeping emerging. In this review, the representative advances in the repair of oral-maxillofacial hard tissues of the past five years are reviewed.

Biofabrication of AuNPs using Coriandrum sativum leaf extract and their antioxidant, analgesic activity.

In this work, Gold nanoparticles (AuNPs) were synthesized by reducing aqueous Au metal ions upon interaction with Coriandrum sativum (C. sativum) leaf extract. The optical absorption peak for the synthesized AuNPs was obtained by using UV-visible spectroscopy within a range of 540-550 nm. The formation of diffraction peaks found at 2θ values of 78.00°, 66.05°, 44.85° and 38.48° that corresponds to the index planes (311), (220), (200), and (111) validate the effective synthesis of AuNPs. Transmission electron microscopy (TEM) was utilized to measure the size range of the spherical shaped nanoparticles, which is obtained to be 32.96 ± 5.25 nm. The peaks obtained from the FTIR results are closely linked to anthocyanins, benzophenones, flavonoids and phenols, which indicated that these biomolecules may serve as reducing agents. Additionally, studies of antioxidant function in vitro revealed that the activities of ABTS (2, 2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) were improved dose-dependently. Further, the results of analgesic analysis showed that the cumulative action of AuNPs and the C. sativum leaf extract in pain relief is more efficient than independent C. sativum leaf extract and the aspirin drug.

Matrix stiffening by self-mineralizable guided bone regeneration.

Collagen membranes produced in vitro with different degrees of intrafibrillar mineralization are potentially useful for guided bone regeneration (GBR). However, highly-mineralized collagen membranes are brittle and difficult for clinical manipulation. The present study aimed at developing an intrafibrillar self-mineralization strategy for GBR membrane by covalently conjugating high-molecular weight polyacrylic acid (HPAA) on Bio-Gide® membranes (BG). The properties of the self-mineralizable membranes (HBG) and their potential to induce bone regeneration were investigated. The HBG underwent the progressive intrafibrillar mineralization as well as the increase in stiffness after immersed in supersaturated calcium phosphate solution, osteogenic medium, or after being implanted into a murine calvarial bone defect. The HBG promoted in-situ bone regeneration via stimulating osteogenic differentiation of mesenchymal stromal cells (MSCs). Hippo signaling was inhibited when MSCs were cultured on the self-mineralized HBG, and in HBG-promoted MSC osteogenesis during in-situ bone regeneration. This resulted in translocation of the transcription co-activators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) into the nucleus to induce transcription of genes promoting osteogenic differentiation of MSCs. Taken together, these findings indicated that HBG possessed the ability to self-mineralize in situ via intrafibrillar mineralization. The increase in stiffness of the extracellular matrix expedited in-situ bone regeneration by inactivating the Hippo-YAP/TAZ signaling cascade. STATEMENT OF SIGNIFICANCE: Guided bone regeneration (GBR) membranes made of naturally derived collagen have been widely used in the bone defect restoration. However, application of collagen GBR membranes run into the bottleneck with the challenges like insufficient stress strength, relatively poor dimensional stability and unsatisfactory osteoinductivity. This study develops a modified GBR membrane that can undergo progressive self-mineralization and matrix stiffening in situ. Increase in extracellular matrix stiffness provides the mechanical cues required for MSCs differentiation and expedites in-situ bone regeneration by inactivating the Hippo-YAP/TAZ signaling cascade.