Search

Achieving optimal implant restoration hinges on both robust osseointegration as the structural foundation and favorable osseoperception for advanced masticatory function. The significance of nerve innervation in the peri‐implant environment as the cornerstone of osseointegration and osseoperception is often underestimated. Despite the integral role of endogenous electric fields (EFs) in the human body, particularly in electrosensitive tissues like nerve tissue, the current approach involving external electrical stimulation is invasive and not clinically applicable. The present study introduces a conductive hydrogel designed to respond to endogenous EFs, aiming to foster nerve regeneration around dental implants to coordinate both osseointegration and osseoperception. The hydrogel promotes neurite outgrowth by upregulating intracellular Ca2+ concentration and activating subsequent pathways. Furthermore, the enhanced release of neuropeptides from neurocells improves the osteogenesis of osteoblasts. The impact of the conductive hydrogel on osseointegration and osseoperception is also thoroughly investigated in vivo. This conductive hydrogel represents a unique strategy for enhancing osseointegration and osseoperception within the endogenous EFs of the peri‐implant environment. This advancement opens the door to achieving the physiological and psychological integration of dental implants. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification. [ABSTRACT FROM AUTHOR]

Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury. Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues. These proteins initiate inflammatory dysfunction, such as neurogenic heterotopic ossification. This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies. Accordingly, a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues. Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis. The relationships among brain-derived extracellular vesicles, fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo. Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo. The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury. [ABSTRACT FROM AUTHOR]

Objectives: The benefits of professional dental treatment for oral diseases have been widely investigated. However, it is unclear whether professional dental treatment provides additional benefits for improving general health. Materials and methods: Data were obtained from the US National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 and 2011 to 2018 cycles. A total of 36,174 participants were included and followed-up for mortality until December 31, 2019. Dental visit behavior was defined as the time interval of last dental visit (TIDV, < 0.5 year, 0.5–1 year, 1–2 years, 2–5 years, and > 5 years) and the main reasons of the last dental visit (treatment, examination, and other reasons). The Cox proportional risk model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: Compared with participants with time interval of less than 0.5 year, the multivariate-adjusted HRs and 95%CI for participants with time interval of more than 5 years were 1.45 (1.31, 1.61) for all-cause mortality (P trend < 0.0001), 1.49 (1.23, 1.80) for cardiovascular diseases mortality (P trend = 0.0009) and 1.53 (1.29, 1.81) for cancer mortality (P trend = 0.013). Compared with dental visit for examination, participants who had their dental visit for treatment had higher risk for mortality. For participants with dental visit for examination, TIDV of less than 1 year showed lower risk for mortality, whereas TIDV of less than 0.5 year is recommend for population with dental visit for treatment. Conclusions: Poor dental visit behavior is associated with an increased risk of mortality. Further well-designed studies are needed to confirm the association between professional dental visit and mortality. Clinical relevance: This study highlights the potential benefits of regular dental visits in maintaining general health. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a degenerative disease characterized by abnormal neurovascularization at the osteochondral junctions, the regulatory mechanisms of which remain poorly understood. In the present study, a murine osteoarthritic model with augmented neurovascularization at the osteochondral junction is used to examine this under‐evaluated facet of degenerative joint dysfunction. Increased extracellular RNA (exRNA) content is identified in neurovascularized osteoarthritic joints. It is found that the amount of exRNA is positively correlated with the extent of neurovascularization and the expression of vascular endothelial growth factor (VEGF). In vitro binding assay and molecular docking demonstrate that synthetic RNAs bind to VEGF via electrostatic interactions. The RNA‐VEGF complex promotes the migration and function of endothelial progenitor cells and trigeminal ganglion cells. The use of VEGF and VEGFR2 inhibitors significantly inhibits the amplification of the RNA‐VEGF complex. Disruption of the RNA‐VEGF complex by RNase and polyethyleneimine reduces its in vitro activities, as well as prevents excessive neurovascularization and osteochondral deterioration in vivo. The results of the present study suggest that exRNAs may be potential targets for regulating nerve and blood vessel ingrowth under physiological and pathological joint conditions. [ABSTRACT FROM AUTHOR]

The advent of biotechnology has expedited the understanding of the biochemistry of deoxyribonucleic acids (DNA). In the past, DNA are thought to be present only in cell nucleus as bearers of the genetic code. With the identification of extracellular DNA in circulating body fluids, DNA are now utilized, at least experimentally, for diagnosis and treatment of diseases. Extracellular DNA of host origin trigger immune responses, and are closely linked to autoimmune disease, cancer‐related inflammation, bacteria adhesion and thrombosis. Recent advancements in DNA nanotechnology have led to the development of a series of DNA‐based materials for treating diseases because of their structural programmability. Current discussions on biosafety and immunogenicity of artificial DNA materials are insufficient. This issue severely restricts the clinical translation of these novel biotechnologies. The present review attempts to bridge the gap between natural extracellular DNA and their derivatives, DNA‐based materials. The pathological attributes of endogenous extracellular DNA motivate the design of targeting DNA materials. In addition, the fate of exogenous DNA in the host inspires the optimization of DNA materials in reducing immune rejection. These bioinspired strategies provide the blueprint for utilizing DNA materials in the management of diseases that are currently challenging to diagnose or treat. [ABSTRACT FROM AUTHOR]

The present study reported a method for inducing incomplete root fracture in human extracted teeth for the purpose of evaluating the merits of different diagnostic imaging techniques. Thirty-five single-rooted teeth were inspected under magnification and transillumination to exclude previously fractured teeth. Tooth crowns were removed, and the root canals were prepared up to the ProTaper Next X4 (40.06) file. Each root was lined with wax and embedded in a polystyrene resin block. The setup was attached to a universal testing machine for pressing a customized conical wedge (diameter at tip: 0.6 mm; taper: 0.2 mm/mm) into the instrumented canal with a 2 kN load at 5 mm/min. The machine was programmed to stop after a sudden 10% drop in loading force. Each specimen was removed from the resin block and inspected under × 20 magnification and transillumination to identify the fracture characteristics (pattern, surfaces and root-third affected). The gap width of each specimen was measured at different locations along the fracture line. The protocol induced incomplete vertical root fractures in all specimens. Fracture widths were < 100 μm in all specimens (mean gap width: 34.9 μm). The proposed methodology was successful in inducing incomplete vertical root fractures with characteristics that resemble the clinical presentation of these conditions. The method is easy to execute, highly reproducible and helps to minimize bias in laboratory studies that aims to mimic vertical root fractures. [ABSTRACT FROM AUTHOR]

Viruses are a major cause of mortality and socio-economic downfall despite the plethora of biopharmaceuticals designed for their eradication. Conventional antiviral therapies are often ineffective. Live-attenuated vaccines can pose a safety risk due to the possibility of pathogen reversion, whereas inactivated viral vaccines and subunit vaccines do not generate robust and sustained immune responses. Recent studies have demonstrated the potential of strategies that combine nanotechnology concepts with the diagnosis, prevention, and treatment of viral infectious diseases. The present review provides a comprehensive introduction to the different strains of viruses involved in respiratory diseases and presents an overview of recent advances in the diagnosis and treatment of viral infections based on nanotechnology concepts and applications. Discussions in diagnostic/therapeutic nanotechnology-based approaches will be focused on H1N1 influenza, respiratory syncytial virus, human parainfluenza virus type 3 infections, as well as COVID-19 infections caused by the SARS-CoV-2 virus Delta variant and new emerging Omicron variant. [ABSTRACT FROM AUTHOR]

Background: Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections. Methods: Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-β-d-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real‑time reverse transcription‑polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo. Results: Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P < 0.01). In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs, but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype (P < 0.05 or P < 0.01). The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways (P < 0.01). In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model (P < 0.01). Conclusions: These findings suggest that Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries. [ABSTRACT FROM AUTHOR]

Fungi and bacteria afflict humans with innumerous pathogen-related infections and ailments. Most of the commonly employed microbicidal agents target commensal and pathogenic microorganisms without discrimination. To distinguish and fight the pathogenic species out of the microflora, novel antimicrobials have been developed that selectively target specific bacteria and fungi. The cell wall features and antimicrobial mechanisms that these microorganisms involved in are highlighted in the present review. This is followed by reviewing the design of antimicrobials that selectively combat a specific community of microbes including Gram-positive and Gram-negative bacterial strains as well as fungi. Finally, recent advances in the antimicrobial immunomodulation strategy that enables treating microorganism infections with high specificity are reviewed. These basic tenets will enable the avid reader to design novel approaches and compounds for antibacterial and antifungal applications. [ABSTRACT FROM AUTHOR]

Tendon–bone interface is prevalent in the human body. It is divided into four zones: tendon (soft tissue), unmineralized fibrocartilage, mineralized fibrocartilage, and bone (hard tissue). Tendon–bone interface is characterized by a cell phenotype gradient that appears in the different zones. The cell phenotype gradients at the tendon–bone interface are orchestrated by specific intracellular molecular mechanisms, extracellular factors, immune signals, and neurovascular factors. These features have inspired scientists to design systems that mimic natural cell phenotype gradients. These biomimetic systems include the construction of cell sheets, regulation of cellular microenvironments, and the design of gradient functional scaffolds. Exploration of methods to mimic cell phenotype gradients is instructional for future clinical applications in reconstituting the tendon–bone interface. The present review elucidates the gradient composition of the tendon–bone interface. The associated regulatory mechanisms and applications are discussed, with the anticipation of creating a mise en scène for future research in interface tissue engineering. [ABSTRACT FROM AUTHOR]

Purpose: The present study evaluated the influence of air entrapment within demineralized dentin on bond strength, nanoleakage, and degree of conversion. Materials and Methods: A vacuum pump with adjustable pressure was used to control the gaseous pressure of a sealed container during the application of a two-step etch-and-rinse adhesive to demineralized dentin. Atmospheric pressure was used as control, and reduced pressures (0.08, 0.06, 0.04 MPa) as experimental variables. Simulated pulpal pressure was adopted during the bonding procedures. After making composite buildups and 24-h water storage, 48 specimens were occlusogingivally sectioned into beams for microtensile bond strength testing, inter- facial morphology observation, and nanoleakage evaluation immediately (6 for each group) or after artificial aging (6 for each group); 20 specimens (5 for each group) were occlusogingivally sectioned into slices for degree of con- version testing. Failure modes were compared using the chi-squared test. The other data were analyzed using ANOVA. Results: When air within composite-dentin interface was thinned with reduced pressures, more thorough adhesive infiltration was achieved, and less distinct nanoleakage as well as higher bond strength were observed compared with control groups, regardless of artificial aging. Mixed failure was predominantly identified, and its percentage was higher in the reduced pressure groups than in the controls. Adhesive application at reduced pressure improved the degree of conversion. Conclusion: Air entrapment in the demineralized dentin adversely affects composite-dentin bonds. Adhesive application at reduced pressure is helpful for reducing entrapped air, thereby improving the durability of composite-dentin bonds. [ABSTRACT FROM AUTHOR]

An ideal tissue‐engineered dermal substitute should possess angiogenesis potential to promote wound healing, antibacterial activity to relieve the bacterial burden on skin, as well as sufficient porosity for air and moisture exchange. In light of this, a glass–ceramic (GC) has been incorporated into chitosan and gelatin electrospun nanofibers (240–360 nm), which MEFs were loaded on it for healing acceleration. The GC was doped with silver to improve the antibacterial activity. The bioactive nanofibrous scaffolds demonstrated antibacterial and superior antibiofilm activities against Gram‐negative and Gram‐positive bacteria. The nanofibrous scaffolds were biocompatible, hemocompatible, and promoted cell attachment and proliferation. Nanofibrous skin substitutes with or without Ag‐doped GC nanoparticles did not induce an inflammatory response and attenuated LPS‐induced interleukin‐6 release by dendritic cells. The rate of biodegradation of the nanocomposite was similar to the rate of skin regeneration under in vivo conditions. Histopathological evaluation of full‐thickness excisional wounds in BALB/c mice treated with mouse embryonic fibroblasts‐loaded nanofibrous scaffolds showed enhanced angiogenesis, and collagen synthesis as well as regeneration of the sebaceous glands and hair follicles in vivo. [ABSTRACT FROM AUTHOR]

Biomimetic approaches utilize natural cell membrane‐derived nanovesicles to camouflage nanoparticles to circumvent some limitations of nanoscale materials. This emergent cell membrane‐coating technology is inspired by naturally occurring intercellular interactions, to efficiently guide nanostructures to the desired locations, thereby increasing both therapeutic efficacy and safety. In addition, the intrinsic biocompatibility of cell membranes allows the crossing of biological barriers and avoids elimination by the immune system. This results in enhanced blood circulation time and lower toxicity in vivo. Macrophages are the major phagocytic cells of the innate immune system. They are equipped with a complex repertoire of surface receptors, enabling them to respond to biological signals, and to exhibit a natural tropism to inflammatory sites and tumorous tissues. Macrophage cell membrane‐functionalized nanosystems are designed to combine the advantages of both macrophages and nanomaterials, improving the ability of those nanosystems to reach target sites. Recent studies have demonstrated the potential of these biomimetic nanosystems for targeted delivery of drugs and imaging agents to tumors, inflammatory, and infected sites. The present review covers the preparation and biomedical applications of macrophage cell membrane‐coated nanosystems. Challenges and future perspectives in the development of these membrane‐coated nanosystems are addressed. [ABSTRACT FROM AUTHOR]

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 Group—38.3 ± 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. [ABSTRACT FROM AUTHOR]

Background: Gluten, a food allergen, is available in foods derived from wheat, rye and barley. It damages the small intestine and causes celiac disease. Herein, we designed a rapid immunochromatographic lateral flow test assay for detecting the gluten contents of raw materials. In this rapid test, the presence of gluten was screened through the capturing of gliadin (a toxic component of gluten) by two identical gliadin monoclonal antibodies. One of the antibodies was immobilized on the membrane in the test zone as a capture reagent. The other antibody was labeled with gold nanoparticles (AuNPs) as a detector reagent. Results: Gold nanoparticles with a size of about 20 nm were synthesized and conjugated to the gliadin monoclonal antibodies. The detection limit of the experimental assay was 20 ppm and positive results were visualized after 15 min using only 40 μL of the extracted sample for each test. Analysis of different flour samples identified the best sensitivity and specificity of the lateral flow test strip (LFTS). Conclusion: The experimental LFTS is an easy-to-use and rapid method for the screening of gluten level in raw materials. The LFTS may be employed to ensure the safety of foods. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effect of CHX pre-treatment on long-term bond strength of fiber posts luted with self-adhesive resin cements. Materials and Methods: Seventy-two single-rooted teeth were selected for root canal treatment and post space preparation. The tested self-adhesive cement/post combinations were (N = 36): 1. RelyX Fiber-Posts luted with RelyX Unicem; 2. Rebilda Posts luted with Bifix SE Cement. For both self-adhesive cements, half of the specimens (experimental groups) were luted after the application of a solution of 2% CHX, while no CHX application was performed for the remaining specimens (control groups). Luted specimens were cut and used for push-out bond strength evaluation immediately, and after storage in artificial saliva for 6 months or 1 year. Additional specimens were processed for quantitative interfacial nanoleakage analysis. Results: ANOVA showed that the variable times of storage had a significant influence on the results (p < 0.05), while no influence of the luting procedure (cements with or without CHX) on the final outcome (p > 0.05) was found. Tukey’s pairwise post-hoc test showed that the radicular bond strength decreased with time of storage. In particular, a significant difference was found between T0 and T1y, but not between T0 and T6m. In contrast, in terms of pre-treatment, no significant reduction in push-out bond strength was observed, irrespective of the aging time. Conclusion: CHX pretreatment did not prevent bond strength degradation of fiber posts luted with self-adhesive cements. [ABSTRACT FROM AUTHOR]

Calcium silicate cements were identified as excellent materials for dentistry, particularly for dental procedures contacting the dental pulp or root system. Both calcium silicate and calcium aluminate cements cause the biomineralization (precipitation of hydroxyapatite [HA] phenomena and shield dental tissues from the underlying cement (a foreign body material). The cements also elute ions to stimulate cytokines that contribute to the healing of the dental pulp or in the tissue surrounding the root of a tooth. The cements serve as a foundation for other dental restorative materials. This paper reviews the cement phases, properties, in vivo reactions, and clinical benefits from the use of calcium silicate and calcium aluminate ceramic cements. [ABSTRACT FROM AUTHOR]

Nanohydroxyapatite (nHAP) has broad applications because of its nanoscopical dimension, large specific surface area, biocompatibility, and low cytotoxicity. Researchers recently discovered that nHAP synthesized in vitro inhibits the growth of different types of tumor cells. Nanohydroxyapatite with potent drug adsorption and loading capacity has potential applications in tumor diagnosis and treatment. Because local tumors and areas of tumor metastasis also produce pathological nHAP in vivo to promote progression and invasion, the role of nHAP in tumorigenesis and development is perceived literature by many as Janus, the double‐faced deity in ancient Roman mythology. In the present review, two types of nHAP (those synthesized in vitro and those produced in vivo) that are affiliated with tumors, their mechanisms in tumor progression as well as their applications in tumor treatment are elucidated to create a backdrop for future research in this exciting, yet controversial arena. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The macrophage is an innate immune defense cell involved in pathogen recognition and clearance. Aim: In view of the diversity of the macrophage phenotype and function, the present study investigated how Enterococcus faecalis infection affects the differentiation, phenotype and cytokine profile of macrophages. Methods: Murine bone marrow-derived stem cells were co-cultured with E. faecalis before and after differentiation. Macrophage M0 polarization towards M1 or M2 was initiated at day 6 by addition of LPS and INF-γ, or IL-4 and IL-13, respectively. Results: E. faecalis did not inhibit macrophage differentiation and were identified within macrophages. Viability of the macrophages infected with E. faecalis prior to differentiation was enhanced, evidenced by apoptosis inhibition, as was expression of CD38 and IRF5 proteins, indicators of M1-like polarization. These M1-like macrophages expressed an aberrant cytokine mRNA profile, with reduction in inflammatory cytokines IL-1β and IL-12 and increase in regulatory cytokine IL-10. No changes in TNF-α or TGF-β1 were detected, compared with the control groups. This atypical M1-like phenotype was retained even upon stimulation with growth factors that normally trigger their development into M2 macrophages. Conclusions: These findings suggested that E. faecalis infection of bone marrow-derived stem cells during differentiation into macrophages induces an atypical M1-like phenotype associated with intracellular bacterial survival. [ABSTRACT FROM AUTHOR]

Excessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibiotic-resistant pathogens. Discussions regarding ionic liquid derivatives in mono-meric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the effects of matrix metalloproteinase-inhibiting solutions and aging methods on the bond strength between resin composite and human dentin. Materials and Methods: Crown segments of 105 human non-carious molars were bonded using simulated pulpal pressure at 20 cm water pressure. The teeth were randomly split into 5 groups according to the solution applied: CG (control, no solution), CHX (0.2% chlorhexidine), EPE (10% ethanolic propolis extract), APE (aqueous propolis extract), and E (70% ethanol). Each solution was left on the acid-etched dentin for 1 min. Adper Single Bond 2 and resin composite (Filtek Z350 XT) were applied to all specimens. The 5 groups were subdivided according to the aging method: SI (sectioned immediately); S (storage in artificial saliva for 6 months); and T (thermomechanical aging with 240,000 mechanical cycles and 1000 thermal cycles). Specimens were sectioned into sticks and subjected to microtensile testing. Bond strength data were analyzed by two-factor ANOVA followed by a post-hoc Tukey's test (α = 0.05). Results: For the factor "solution" , there was no significant difference among the groups (p = 0.32). For the factor "aging method" , significant differences were found (p < 0.001), with the following mean bond strengths (MPa): SI: 31.1; S: 24.4; T: 26.8. Conclusions: The use of matrix metalloproteinase-inhibiting solutions on dentin as an adjunct to the application of an etch-and-rinse adhesive does not prevent the loss of bond strength after aging. Nevertheless, these solutions have no adverse effect on adhesion to tooth structure. [ABSTRACT FROM AUTHOR]

Gene therapy provides a promising strategy for curing monogenetic disorders and complex diseases. However, there are challenges associated with the use of viral delivery vectors. The advent of nanomedicine represents a quantum leap in the application of gene therapy. Recent advances in stimulus‐responsive nonviral nanocarriers indicate that they are efficient delivery systems for loading and unloading of therapeutic nucleic acids. Some nanocarriers are responsive to cues derived from the internal environment, such as changes in pH, redox potential, enzyme activity, reactive oxygen species, adenosine triphosphate, and hypoxia. Others are responsive to external stimulations, including temperature gradients, light irradiation, ultrasonic energy, and magnetic field. Multiple stimuli‐responsive strategies have also been investigated recently for experimental gene therapy. [ABSTRACT FROM AUTHOR]

The oral cavity and oropharynx are complex environments that are susceptible to physical, chemical, and microbiological insults. They are also common sites for pathological and cancerous changes. The effectiveness of conventional locally‐administered medications against diseases affecting these oral milieus may be compromised by constant salivary flow. For systemically‐administered medications, drug resistance and adverse side‐effects are issues that need to be resolved. New strategies for drug delivery have been investigated over the last decade to overcome these obstacles. Synthesis of nanoparticle‐containing agents that promote healing represents a quantum leap in ensuring safe, efficient drug delivery to the affected tissues. Micro/nanoencapsulants with unique structures and properties function as more favorable drug‐release platforms than conventional treatment approaches. The present review provides an overview of newly‐developed nanocarriers and discusses their potential applications and limitations in various fields of dentistry and oral medicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of different surface treatments on the tensile bond strength between lithium disilicate glass-ceramics, resin cement, and dentin. Fifty truncated cone-shape glass-ceramics were divided into five groups (n = 10): G1, control: 10% hydrofluoric acid (HF); G2, Nd:YAG laser + silane; G3, Sil + Nd:YAG laser; G4, graphite + Nd:YAG laser + Sil; and G5, graphite + Sil + Nd:YAG laser. Fifty human third-molars were cut to cylindrical shape and polished to standardize the bonding surfaces. The glass-ceramic specimens were bonded to dentin with a dual-cured resin cement and stored in distilled water for 24 h at 37ºC. Tensile testing was performed on a universal testing machine (10 Kgf load cell at 1 mm/min) until failure. The bond strength values (mean ± SD) in MPa were G1 (9.4 ± 2.3), G2 (9.7 ± 2.0), G3 (6.7 ± 1.9), G4 (4.6 ± 1.1), and G5 (1.2 ± 0.3). Nd:YAG laser and HF improve the bond strength between lithium disilicate glass-ceramics, resin cement, and dentin. The application of a graphite layer prior to Nd:YAG laser irradiation negatively affects this bonding and presented inferior results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bilateral communication between bone and nerves is crucial for optimal repair of large bone defects as well as repair of peripheral nerves within the skeleton. However, simultaneous regeneration of bone and nerves is an issue that has long been overlooked in prior literature. Incongruous or even contradictory requirements or regeneration environments for bone and nerves make simultaneous regeneration of multiple tissues challenging. The present review commences with introducing natural crosstalk between bone and nerves, highlighting the rationale for simultaneous regeneration of bone and nerves. These issues will pave the way for the development of inspirational materials design concepts that capitalize on the principles of osteoconduction, osteoinduction, neuroconduction, neuroinduction, and neuroattraction. Potential strategies based on selection of appropriate scaffolds, acellular biological factors and architectural design will be addressed. [ABSTRACT FROM AUTHOR]

Objectives: Bisphosphonate‐related osteonecrosis of the jaw (BRONJ) is a severe complication of systemic nitrogen‐containing bisphosphonate (N‐BP) administration, which leads to osteonecrosis, pain, and infection. Despite much effort, effective remedies are yet to be established. This study aimed to investigate potential recovery effect of borate bioactive glass (BBG) in vitro and in vivo. Methods: The effect of BBG on zoledronate‐treated bone marrow mesenchymal cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) was explored by cell counting kit‐8, EdU assay, flow cytometry, alkaline phosphatase staining, alizarin red staining, angiogenesis experiment, and real‐time quantitative polymerase chain reaction. The preventive effect of BBG on zoledronate‐induced osteonecrosis of the jaw in rat model was examined by micro‐CT, HE staining, and immunohistochemistry. Results: Exposure of BBG to BMSCs and HUVECs increased cell proliferation and restored their osteogenesis and angiogenesis potential in vitro. The BRONJ lesions were satisfactorily repaired and bone mineral density, bone volume/tissue volume, trabecula number, OCN‐positive cells, and CD31‐positive cells were increased in the BBG‐treated groups compared with saline‐treated groups. Conclusions: Exposure of BMSCs and HUVECs to BBG restores osteogenesis and angiogenesis inhibited by zoledronate. BBG successfully restores extraction socket healing of BRONJ in rat model. [ABSTRACT FROM AUTHOR]

In the progression of osteoarthritis, pathological calcification in the affected joint is an important feature. The role of these crystallites in the pathogenesis and progression of osteoarthritis is controversial; it remains unclear whether they act as a disease initiator or are present as a result of joint damage. Recent studies reported that the molecular mechanisms regulating physiological calcification of skeletal tissues are similar to those regulating pathological or ectopic calcification of soft tissues. Pathological calcification takes place when the equilibrium is disrupted. Calcium phosphate crystallites are identified in most affected joints and the presence of these crystallites is closely correlated with the extent of joint destruction. These observations suggest that pathological calcification is most likely to be a disease initiator instead of an outcome of osteoarthritis progression. Inhibiting pathological crystallite deposition within joint tissues therefore represents a potential therapeutic target in the management of osteoarthritis. [ABSTRACT FROM AUTHOR]

Microbial colonization on material surfaces is ubiquitous. Biofilms derived from surface‐colonized microbes pose serious problems to the society from both an economical perspective and a health concern. Incorporation of antimicrobial nanocompounds within or on the surface of materials, or by coatings, to prevent microbial adhesion or kill the microorganisms after their attachment to biofilms, represents an important strategy in an increasingly challenging field. Over the last decade, many studies have been devoted to preparing meta‐based nanomaterials that possess antibacterial, antiviral, and antifungal activities to combat pathogen‐related diseases. Herein, an overview on the state‐of‐the‐art antimicrobial nanosized metal‐based compounds is provided, including metal and metal oxide nanoparticles as well as transition metal nanosheets. The antimicrobial mechanism of these nanostructures and their biomedical applications such as catheters, implants, medical delivery systems, tissue engineering, and dentistry are discussed. Their properties as well as potential caveats such as cytotoxicity, diminishing efficacy, and induction of antimicrobial resistance of materials incorporating these nanostructures are reviewed to provide a backdrop for future research. [ABSTRACT FROM AUTHOR]

Gum polysaccharides are derived from renewable sources. They are readily available, inexpensive, non-hazardous and eco-friendly. Depending upon the source, gums may be categorized as microbial gums, plant exudate gums or seed gums. Naturally occurring gum carbohydrates find multiple applications in the biomedical arena, compared with synthetic compounds, because of their unique structures and functionalities. Gums and their biocomposites are preferred for sustained drug delivery because they are safe and edible as well as more susceptible to biodegradation. The present review provides a state-of-the-art conspectus on the industrial and biomedical applications of antimicrobial gum-based biocomposites. Different kinds of gums polysaccharides will first be addressed based on their sources. Metal-, carbon- and organic-based nanostructures that are used in gum nanocomposites will then be reviewed with respect to their industrial and biomedical applications, to provide a backdrop for future research. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the effect of chlorhexidine (CHX) incorporation into experimental dentin adhesives with different hydrophilicities on the microtensile bond strength (µTBS) to dentin. Materials and Methods: Flat, deep dentin surfaces were prepared from 60 extracted human third molars. Three ethanol-solvated (50 wt% ethanol/50 wt% comonomers) experimental adhesives with varying degrees of hydrophilicity were prepared for the CHX-free groups. For the CHX-containing groups, chlorhexidine diacetate was further added to the ethanol-solvated adhesives to form a concentration of 2.0 wt% CHX. Dentin surfaces were etched with 37% phosphoric acid for 15 s, rinsed and blot dried before bonding. The adhesives were generously applied to dentin with a microbrush for 15 s. A second application of fresh adhesive was made and light cured for 20 s (600 mW/cm²) after solvent evaporation. Composite buildups were made using Filtek Z250 (3M ESPE). The bonded teeth were sectioned into 0.9 mm x 0.9 mm beams and stressed to failure at a crosshead speed of 1 mm/min. Testing was performed 24 h after specimen preparation and 12 months after storage in artificial saliva. The µTBS data were analyzed using three-way ANOVA and Tukey's multiple comparison tests. Fractographic analysis was performed by SEM. Results: Significant differences were observed for the three factors "adhesive hydrophilicity" (p < 0.001), "CHX incorporation" (p = 0.001), and "storage time" (p < 0.001). Interaction among these three factors was also significant (p < 0.001). Incorporation of CHX had no effect on the immediate bond strength of the three experimental adhesives (p > 0.05). After storage in artificial saliva, significant reduction in bond strength was observed in all adhesive groups, except for CHX-containing adhesive I (p < 0.001). The µTBS of the CHX-containing experimental adhesive III was significantly higher than the corresponding CHX-free adhesive (p < 0.001) after aging. Conclusion: When incorporated into hydrophilic dental adhesives, chlorhexidine can partially reduce the degradation of the resin-dentin bonds. [ABSTRACT FROM AUTHOR]