Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s...Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s disease(AD). The blood-brain barrier(BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1(Cav-1) expression was enhanced after P. gingivalis infection.Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain(RgpA) were detected.Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a(Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.展开更多
The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the r...The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.展开更多
Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials.Here bioinspired ma...Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials.Here bioinspired magnesium composites with fish-scale-like orthogonal plywood and double-Bouligand architectures were developed by pressureless infiltration of a magnesium melt into the woven contextures of continuous titanium fibers.The composites exhibit enhanced strength and work-hardening ability compared to those estimated from a simple mixture of their constituents at ambient to elevated temperatures.In particular,the double-Bouligand architecture can effectively deflect cracking paths,alleviate strain localization,and adaptively reorient titanium fibers within the magnesium matrix during the deformation of the composite,representing a successful implementation of the property-optimizing mechanisms in fish scales.The strength of the composites,specifically the effect of their bioinspired architectures,was interpreted based on the adaptation of classical laminate theory.This study may offer a feasible approach for developing new bioinspired metal-matrix composites with improved performance and provide theoretical guidance for their architectural designs.展开更多
Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immun...Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.展开更多
The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists.The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral...The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists.The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers,based on factors such as detailed clinical medical history inquiry,histopathological examination,and ulceration-related systemic diseases screening.Not only it can provide a standardized procedure of oral ulceration,but also it can improve the diagnostic efficiency,in order to avoid misdiagnosis and missed diagnosis.展开更多
Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis,has been shown to accelerate the progression of atherosclerosis(AS).However,the definite mechanisms remain elusive.Emerging evidence supports an a...Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis,has been shown to accelerate the progression of atherosclerosis(AS).However,the definite mechanisms remain elusive.Emerging evidence supports an association between mitochondrial dysfunction and AS.In our study,the impact of P.gingivalis on mitochondrial dysfunction and the potential mechanism were investigated.The mitochondrial morphology of EA.hy926 cells infected with P.gingivalis was assessed by transmission electron microscopy,mitochondrial staining,and quantitative analysis of the mitochondrial network.Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species(mtROS)and mitochondrial membrane potential(MMP)levels.Cellular ATP production was examined by a luminescence assay kit.The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence.Mdivi-1,a specific Drp1 inhibitor,was used to elucidate the role of Drp1 in mitochondrial dysfunction.Our findings showed that P.gingivalis infection induced mitochondrial fragmentation,increased the mtROS levels,and decreased the MMP and ATP concentration in vascular endothelial cells.We observed upregulation of Drp1(Ser616)phosphorylation and translocation of Drp1 to mitochondria.Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P.gingivalis.Collectively,these results revealed that P.gingivalis infection promoted mitochondrial fragmentation and dysfunction,which was dependent on Drp1.Mitochondrial dysfunction may represent the mechanism by which P.gingivalis exacerbates atherosclerotic lesions.展开更多
Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known t...Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known to induce inflammatory responses.To explore the pathological relationships between PPAD and UC,we used homologous recombination technology to construct a P.gingivalis strain in which the PPAD gene was deleted(Δppad)and aΔppad strain in which the PPAD gene was restored(comΔppad).C57 BL/6 mice were orally gavaged with saline,P.gingivalis,Δppad,or comΔppad twice a week for the entire 40 days(days 0-40),and then,UC was induced by dextran sodium sulfate(DSS)solution for 10 days(days 31-40).P.gingivalis and comΔppad exacerbated DDS-induced colitis,which was determined by assessing the parameters of colon length,disease activity index,and histological activity index,butΔppad failed to exacerbate DDS-induced colitis.Flow cytometry and ELISA revealed that compared withΔppad,P.gingivalis,and comΔppad increased T helper 17(Th17)cell numbers and interleukin(IL)-17 production but decreased regulatory T cells(Tregs)numbers and IL-10 production in the spleens of mice with UC.We also cocultured P.gingivalis,Δppad,or comΔppad with T lymphocytes in vitro and found that P.gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers.Immunofluorescence staining of colon tissue paraffin sections also confirmed these results.The results suggested that P.gingivalis exacerbated the severity of UC in part via PPAD.展开更多
Magnesium(Mg) alloys have attracted a wealth of attention in orthopedic fields for their superior mechanical properties, degradability,and excellent biocompatibility. Consistently, to resolve the issues on rapid degra...Magnesium(Mg) alloys have attracted a wealth of attention in orthopedic fields for their superior mechanical properties, degradability,and excellent biocompatibility. Consistently, to resolve the issues on rapid degradation, more studies are dedicated to the researches on the composition design, preparation and processing, surface modification, the degradation modes of Mg alloys. Nevertheless, the mechanisms by which Mg alloys promote bone healing remain elusive. This review gives an account of specific mechanisms on Mg alloys promoting bone healing from four aspects, immunomodulatory, angiogenesis, osteogenesis and regulation of osteoclast function. We highlight the regulation of Mg alloys on the functional status and interactions of numerous cells that are involved in bone healing, including immune cells, osteogenicrelated cells, osteoclasts, endothelial cells(ECs), nerve cells, etc., and summarize the signaling pathways involved, with the aim to provide the basis and support on future investigation on mechanisms on Mg alloys driving bone regeneration. More importantly, it provides a rationale and a general new basis for the application of Mg alloys in orthopedic fields.展开更多
In this work,microbiologically influenced corrosion(MIC)of 316 L stainless steel(SS)caused by oral microbiota was investigated with HOMINGS 16 S rRNA gene sequencing technology,and electrochemical and surface analysis...In this work,microbiologically influenced corrosion(MIC)of 316 L stainless steel(SS)caused by oral microbiota was investigated with HOMINGS 16 S rRNA gene sequencing technology,and electrochemical and surface analysis techniques.The results showed that oral microbiota from different subjects developed multi-species biofilms with significant differences in structure and composition of bacteria strains on the316 L SS coupons.In the presence of oral microbiota,more severe pitting corrosion and faster dissolution of metallic ions including Ni and Cr were observed.The biofilm considerably decreased the pitting potential of 316 L SS from 1268.0±29.1 mV vs.SCE(abiotic control)to less than 500 mV vs.SCE.The corrosion current density in the presence of oral microbiota from subject 1(115.3±83.3 nA cm^(-2))and subject 2(184.4±162.0 nA cm^(-2))was at least 4 times more than that in the abiotic medium(28.0±2.3 nA cm^(-2)).The electroactive microorganisms with the potential to facilitate corrosion via extracellular electron transfer found in oral microbiota may be mainly responsible for the accelerated corrosion.展开更多
Ti6Al4V3Cu alloy is a promising biomaterial for combating implant-related infection.However,the antibacterial property of Ti6Al4V3Cu is expected to be enhanced due to the low content of Cu element in titanium.To addre...Ti6Al4V3Cu alloy is a promising biomaterial for combating implant-related infection.However,the antibacterial property of Ti6Al4V3Cu is expected to be enhanced due to the low content of Cu element in titanium.To address this issue,the antibacterial property of Ti6Al4V3Cu was tailored by the grooves with different groove widths(30μm,60μm,and 90μm)that were constructed on the surface of the Ti6Al4V3Cu by selective laser melting.The effect of grooves on corrosion resistance,antibacterial property,and cytocompatibility was investigated.The electrochemical tests showed that the corrosion resistance decreased with increasing groove width.The antibacterial tests indicated that the groove with a width of 30μm and 90μm groups showed better antibacterial activity against S.aureus(>90%)compared with the groove with a width of 60μm.The in vitro study suggested that all samples with different grooves were found to exhibit good cytocompatibility with osteoblast cells.It is considered that creating grooves on Ti6Al4V3Cu by selective laser melting is a promising strategy to enhance the antibacterial activity without sacrificing cytocompatibility.展开更多
Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans i...Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans is a critical pathogenic microorganism that causes dental caries.This work investigated the corrosive effects of S.mutans on TC4 and functional gradient TC4/TC4-5Cu coupons fabricated by selective laser melting(SLM)through various electrochemical measurements,surface examination,observation of biofilm and corrosion analysis.The results indicated that the Cu-bearing alloy showed an inhibitory effect on the biofilms due to the release of Cu element,thereby reducing the corrosion rate of MIC.The corrosion current density(icorr)of TC4(11.7±0.8)nA cm−2 is higher than that of TC4/TC4-5Cu(7.4±0.4)nA cm−2 in the presence of S.mutans,while the maximum pit depth of TC4 is 1.6 times that of TC4/TC4-5Cu.Therefore,metal modification through Cu alloying is an effective strategy to improve the MIC resistance.展开更多
Biodegradable magnesium alloys have been turned out to be a promising candidate for orthopedic applications.In this study,the mechanical properties,degradation behaviorand cytocompatibility of MgZn-Zr-Nd and Mg-Zn-Zr-...Biodegradable magnesium alloys have been turned out to be a promising candidate for orthopedic applications.In this study,the mechanical properties,degradation behaviorand cytocompatibility of MgZn-Zr-Nd and Mg-Zn-Zr-Y alloys were studied in comparison with pure Mg.Mechanical tests showed that the strength and ductility of Mg-Zn-Zr-Nd and Mg-Zn-Zr-Y alloys were excellent.The corrosion resistance analyzed by electrochemical test and immersion test in alpha modified eagle(α-MEM) medium with 10% fetal bovine serum(FBS) revealed the degradation of Mg-Zn-Zr-Nd and Mg-Zn-Zr-Y alloys were faster than pure Mg at an early stage but slowed down after long time immersion.The metal ion concentrations were consistent with the corrosion rate.Mg-Zn-Zr-Nd alloy shows better mechanical properties than pure Mg and better corrosion resistance than Mg-Zn-Zr-Y alloy.The direct and indirect in vitro tests with MC3 T3-E1 cells demonstrate that Mg-Zn-Zr-Nd shows the best cytocompatibility and osteogenesis.The results suggest that Mg-Zn-Zr-Nd alloy shows an ideal combination of mechanical,corrosive and biological properties.In summary,these results implying the Mg-Zn-Zr-Nd alloy has great potential to benefit the future development of orthopedic applications.展开更多
Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research.Barium titanate(BT)is an electroactive material that can generate electrical s...Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research.Barium titanate(BT)is an electroactive material that can generate electrical signals in response to applied mechanical forces.In this study,a BT piezoelectric ceramic coating was synthesized on the surface of a TC4 titanium alloy,forming a BT/TC4 material,and low-intensity pulsed ultrasound(LIPUS)was then applied as a mechanical stimulus.The combined effects on the biological responses of MC3T3-E1 cells were investigated.Results of scanning electron microscopy,energy-dispersive X-ray spectroscopy,and X-ray diffraction showed that an uniform nanospheres-shaped BT coating was formed on TC4 substrate.Piezoelectric behaviors were observed using piezoelectric force microscopy with the piezoelectric coefficient d_(33)of 0.42 pC/N.Electrochemical measures indicated that LIPUS-stimulated BT/TC4 materials could produce a microcurrent of approximately 10μA/cm^(2).In vitro,the greatest osteogenesis(cell adhesion,proliferation,and osteogenic differentiation)was found in MC3T3-E1 cells when BT/TC4 was stimulated using LIPUS.Furthermore,the intracellular calcium ion concentration increased in these cells,possibly because opening of the L-type calcium ion channels was promoted and expression of the Ca_(V)1.2 protein was increased.Therefore,the piezoelectric BT/TC4 material with LIPUS loading synergistically promoted osteogenesis,rending it a potential treatment for early stage formation of reliable bone-implant contact.展开更多
Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent...Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent candidate for orthopedic appliances recently. But the high degradation rate is still a big problem. Making a biodegradable coating with good biocompatibility to slow down the degeneration rate of magnesium is one of the best methods. However, protective coatings will impair the antibacterial effects of magnesium which is caused by the rise of p H value throughout its degradation. To solve this problem, a series of composite coatings with different amounts of Cu O particles(3, 5 and 7 wt.%) were fabricated on pure magnesium through plasma electrolytic oxidation(PEO) to investigate in vitro biocompatibility and the antibacterial abilities against Porphyromonas gingivalis(P. gingivalis). Surface characterization and degradation behavior of the copper-bearing PEO coatings were also systematically studied. Furthermore,the most optimum coating was also systematically studied by X-ray photoelectron spectroscopy(XPS)and electrochemical corrosion test. Results of the present research revealed that adding proper amount of Cu O into PEO coatings could greatly improve the antibacterial abilities of the PEO coatings. The antibacterial activities of copper-bearing PEO coatings were excellent and revealed concentration-dependent and time-dependent. Biocompatibility of copper-bearing PEO coatings showed that proper amount of Cu could promote cell proliferation. Compared with other PEO coatings in this study, PEO-7 Cu showed some inhibition effects on cell proliferation and adhesion for long-term use. Electrochemical corrosion tests and immersion tests showed that PEO-5 Cu and PEO-7 Cu copper-bearing PEO coatings would provide satisfying corrosion resistance effects, while PEO-3 Cu was poorer than PEO coatings without Cu. However, compared with uncoated pure magnesium, the corrosion resistance of the PEO coating was much better. Based on the results of antibacterial ability, biocompatibility, and corrosion resistance of the above copper-bearing PEO coatings, PEO-5 Cu in this research was recommended to be used in patients with jaw defects.展开更多
In order to reduce implant-related infections and improve early osseointegration,we performed HF+anodic oxidation on the surface of the new antibacterial Ti-Cu alloy to make the titanium-based implants have a micro/su...In order to reduce implant-related infections and improve early osseointegration,we performed HF+anodic oxidation on the surface of the new antibacterial Ti-Cu alloy to make the titanium-based implants have a micro/submicron structure.On this basis,a series of surface-modified Ti-x Cu alloys with different Cu contents(3,5 and 7 wt%)were fabricated and a comprehensive study was conducted on MC3 T3-E1 cell adhesion,proliferation,apoptosis and its antibacterial activity against Staphylococcus aureus.Results showed that the Ti-x Cu alloys by HF etching+anodized possessed multifunctional characteristics of antibiofilm and antibacterial abilities,excellent biocompatibility and osteogenesis promoting abilities.Increment of Cu content significantly contributed to the antibacterial and osteogenic properties of HF etching+anodized Ti-Cu alloys.Cell proliferation rates of HF etching+anodized Ti-7 Cu alloys were lower than those of Ti-3 Cu and Ti-5 Cu alloys,while the early cell apoptosis rates were higher than Ti-3 Cu and Ti-5 Cu groups.All the above results finally presented that the HF etching+anodized Ti-5 Cu alloy exhibited extremely strong antibacterial properties,good biological compatibility and osteogenic ability,as well as the most excellent ductility and corrosion resistance,providing a great potential application for the future dental implantation.展开更多
Streptococcus mutans(S.mutans)is the most common cariogenic bacteria and causes caries by forming biofilms.A novel gradient Cu-bearing titanium alloy(TC4-5Cu/TC4)was manufactured using selective laser melting(SLM)tech...Streptococcus mutans(S.mutans)is the most common cariogenic bacteria and causes caries by forming biofilms.A novel gradient Cu-bearing titanium alloy(TC4-5Cu/TC4)was manufactured using selective laser melting(SLM)technology for dental applications,which is anticipated to inhibit the formation of biofilm.In this study,the released concentration of copper ions in both minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)was tested in order to assess the antibacterial property of the alloy against planktonic S.mutans,and the antibacterial and antibiofilm efficiencies of TC4-5Cu/TC4 alloy against sessile S.mutans were evaluated via quantitative antibacterial tests and biofilm determination.Reverse transcription polymerase chain reaction(RT-PCR)was performed to analyze the expression of biofilm-related genes(gtfB,gtfC,gtfD,ftf and gbpB)and acid production-related gene(ldh).The results suggested that the MIC and MBC of Cu^(2+)were much higher than the release concentration of copper ions of the alloy,which was consistent with the lack of antibacterial effect against planktonic bacteria.On the contrary,TC4-5Cu/TC4 alloy exhibited significant bactericidal property against the sessile bacteria and efficient biofilm-restrained ability,and all genes detected in this research were down-regulated.The results indicated that the TC4-5Cu/TC4 alloy suppressed biofilm formation and the sessile bacterial viability by down-regulating biofilm-related genes.展开更多
The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degrad...The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.展开更多
Friction and wear performance is critical for dental materials which are inevitably subject to reciprocating friction against opposing teeth in applications.Here in-vitro friction and wear behavior of bioinspired cera...Friction and wear performance is critical for dental materials which are inevitably subject to reciprocating friction against opposing teeth in applications.Here in-vitro friction and wear behavior of bioinspired ceramic-polymer composites,which possess nacre-like lamellar and brick-and-mortar architectures and resemble human teeth in their stiffness and hardness,against human tooth enamel were quantitatively investigated to imitate actual service conditions in line with standardized testing configuration.The composites were revealed to exhibit different wear mechanisms and lead to differing extents of wear to the opposing tooth enamel depending on their specific architectural types and orientations.In particular,the brick-and-mortar architecture displayed much less wear than the lamellar one,without obviously roughening the contact surfaces with enamel owing to its high ceramic content,and as such did not accelerate the wear of enamel as compared to smooth ceramics.Such characteristics,combined with its unique stiffness and hardness matching those of human enamel as well as the good fracture toughness and machinability,endow the composite with a promising potential for dental applications.This work may provide an experimental basis to this end and may also give insights towards designing new bioinspired wear-resistant materials for reducing friction and wear.展开更多
Mg(and Mg alloys)and Ti(and Ti alloys)are two important classes of metallic implant materials which are respectively completely degradable and non-degradable after implantation.Making composites composed of them offer...Mg(and Mg alloys)and Ti(and Ti alloys)are two important classes of metallic implant materials which are respectively completely degradable and non-degradable after implantation.Making composites composed of them offers the promise for combining their property advantages for bone repair.Here,we present a Mg-Ti composite fabricated by pressureless infiltration of pure Mg melt into 3D printed Ti scaffold,and demonstrate a potential of the composite for use as new partially degradable and bioactive implant materials.The composite has such architecture that the Mg and Ti phases are topologically bicontinuous and mutually interspersed in 3D space,and exhibits several advantages over its constituents,such as higher strengths than as-cast pure Mg and Ti scaffold along with lower Young’s modulus than dense Ti.Additionally,the degradation of Mg phase may induce the formation and ingrowth of new bone tissues into the Ti scaffold to form mechanical interlocking between them;in this process,the Ti scaffold provides constant support and Young’s modulus adaptively decreases toward that of bone.Despite the accelerated corrosion than pure Mg,the composite remains non-cytotoxic and does not cause obvious adverse reactions after implantation as revealed by in vitro and in vivo experiments.This study may offer a new possibility for combining mechanical durability and bioactivity in implant materials,and allow for customized and targeted design of the implant.展开更多
Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the do...Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated.Here,by utilizing different annealing temperatures prior to corona poling treatment,BaTiO_(3)/P(VDF-TrFE)ferroelectric nanocomposite membranes with varying charge polarization intensity(d_(33)≈0,4,12 and 19 pC N^(-1))were fabricated.Enhanced expression of neural markers,increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation.Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx,focal adhesion formation,FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge.Hence,this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.展开更多
基金supported by Scientific Research Funding Project of Education Department of Liaoning Province [grant number LJKZ0782]National Natural Science Foundation of China [grant numbers 81670999]。
文摘Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer’s disease(AD). The blood-brain barrier(BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1(Cav-1) expression was enhanced after P. gingivalis infection.Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain(RgpA) were detected.Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a(Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
基金supported by the National Natural Science Foundation of China,No.81771351the National Key R&D Program of China,No.2017YFA0105802+1 种基金the Joint Research Fund Liaoning-Shenyang National Laboratory for Materials Science,No.2019JH3/30100022the National Science Foundation for Post-doctoral Scientists of China,No.2018M641732(all to QA and LLW)。
文摘The functional properties of endogenous Schwann cells(SCs)during nerve repair are dynamic.Optimizing the functional properties of SCs at different stages of nerve repair may have therapeutic benefit in improving the repair of damaged nerves.Previous studies showed that miR-221-3p promotes the proliferation and migration of SCs,and miR-338-3p promotes the myelination of SCs.In this study,we established rat models of sciatic nerve injury by bridging the transected sciatic nerve with a silicone tube.We injected a miR-221 lentiviral vector system together with a doxycycline-inducible Tet-On miR-338 lentiviral vector system into the cavity of nerve conduits of nerve stumps to sequentially regulate the biological function of endogenous SCs at different stages of nerve regeneration.We found that the biological function of SCs was sequentially regulated,the diameter and density of myelinated axons were increased,the expression levels of NF200 and myelin basic protein were increased,and the function of injured peripheral nerve was improved using this system.miRNA Target Prediction Database prediction,Nanopore whole transcriptome sequencing,quantitative PCR,and dual luciferase reporter gene assay results predicted and verified Cdkn1b and Nrp1 as target genes of miR-221-3p and miR-338-3p,respectively,and their regulatory effects on SCs were confirmed in vitro.In conclusion,here we established a new method to enhance nerve regeneration through sequential regulation of biological functions of endogenous SCs,which establishes a new concept and model for the treatment of peripheral nerve injury.The findings from this study will provide direct guiding significance for clinical treatment of sciatic nerve injury.
基金the financial support by the National Key R&D Program of China under grant number 2020YFA0710404the National Natural Science Foundation of China under grant number 51871216+6 种基金the KC Wong Education Foundation(GJTD-2020-09)the Liao Ning Revitalization Talents Programthe State Key Laboratory for Modification of Chemical Fibers and Polymer Materials at Donghua Universitythe Opening Project of Jiangsu Province Key Laboratory of High-End Structural Materials under grant number hsm1801the Opening Project of National Key Laboratory of Shock Wave and Detonation Physics under grant number 6142A03203002the Youth Innovation Promotion Association CASsupported by the Multi-University Research Initiative under grant number AFOSR-FA9550-151-0009 from the Air Force Office of Scientific Research
文摘Natural fish scales demonstrate outstanding mechanical efficiency owing to their elaborate architectures and thereby may serve as ideal prototypes for the architectural design of man-made materials.Here bioinspired magnesium composites with fish-scale-like orthogonal plywood and double-Bouligand architectures were developed by pressureless infiltration of a magnesium melt into the woven contextures of continuous titanium fibers.The composites exhibit enhanced strength and work-hardening ability compared to those estimated from a simple mixture of their constituents at ambient to elevated temperatures.In particular,the double-Bouligand architecture can effectively deflect cracking paths,alleviate strain localization,and adaptively reorient titanium fibers within the magnesium matrix during the deformation of the composite,representing a successful implementation of the property-optimizing mechanisms in fish scales.The strength of the composites,specifically the effect of their bioinspired architectures,was interpreted based on the adaptation of classical laminate theory.This study may offer a feasible approach for developing new bioinspired metal-matrix composites with improved performance and provide theoretical guidance for their architectural designs.
基金supported by grants from the National Key R&D Program of China (2016YFC1102800)National Natural Science Foundation of China (81879741, 51872332)+1 种基金Natural Science Foundation of Liaoning Province (20170541040)China Postdoctoral Science Foundation Grant (2020M681020)
文摘Distraction osteogenesis(DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
基金supported by grants from the National Natural Science Foundations of China(No.U19A2005,81771081,81870775)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-12M-5-004,2020-I2M-C&T-A-023)。
文摘The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists.The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers,based on factors such as detailed clinical medical history inquiry,histopathological examination,and ulceration-related systemic diseases screening.Not only it can provide a standardized procedure of oral ulceration,but also it can improve the diagnostic efficiency,in order to avoid misdiagnosis and missed diagnosis.
基金supported by grants from National Natural Science Foundation of China(NO.81970943,81870771)。
文摘Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis,has been shown to accelerate the progression of atherosclerosis(AS).However,the definite mechanisms remain elusive.Emerging evidence supports an association between mitochondrial dysfunction and AS.In our study,the impact of P.gingivalis on mitochondrial dysfunction and the potential mechanism were investigated.The mitochondrial morphology of EA.hy926 cells infected with P.gingivalis was assessed by transmission electron microscopy,mitochondrial staining,and quantitative analysis of the mitochondrial network.Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species(mtROS)and mitochondrial membrane potential(MMP)levels.Cellular ATP production was examined by a luminescence assay kit.The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence.Mdivi-1,a specific Drp1 inhibitor,was used to elucidate the role of Drp1 in mitochondrial dysfunction.Our findings showed that P.gingivalis infection induced mitochondrial fragmentation,increased the mtROS levels,and decreased the MMP and ATP concentration in vascular endothelial cells.We observed upregulation of Drp1(Ser616)phosphorylation and translocation of Drp1 to mitochondria.Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P.gingivalis.Collectively,these results revealed that P.gingivalis infection promoted mitochondrial fragmentation and dysfunction,which was dependent on Drp1.Mitochondrial dysfunction may represent the mechanism by which P.gingivalis exacerbates atherosclerotic lesions.
基金supported by grants from the National Natural Science Foundation of China(81870771)the plan of the talents for Liaoning development(XLYC1802129)。
文摘Abstract:Ulcerative Colitis(UC)has been reported to be related to Porphyromonas gingivalis(P.gingivalis).Porphyromonas gingivalis peptidylarginine deiminase(PPAD),a virulence factor released by P.gingivalis,is known to induce inflammatory responses.To explore the pathological relationships between PPAD and UC,we used homologous recombination technology to construct a P.gingivalis strain in which the PPAD gene was deleted(Δppad)and aΔppad strain in which the PPAD gene was restored(comΔppad).C57 BL/6 mice were orally gavaged with saline,P.gingivalis,Δppad,or comΔppad twice a week for the entire 40 days(days 0-40),and then,UC was induced by dextran sodium sulfate(DSS)solution for 10 days(days 31-40).P.gingivalis and comΔppad exacerbated DDS-induced colitis,which was determined by assessing the parameters of colon length,disease activity index,and histological activity index,butΔppad failed to exacerbate DDS-induced colitis.Flow cytometry and ELISA revealed that compared withΔppad,P.gingivalis,and comΔppad increased T helper 17(Th17)cell numbers and interleukin(IL)-17 production but decreased regulatory T cells(Tregs)numbers and IL-10 production in the spleens of mice with UC.We also cocultured P.gingivalis,Δppad,or comΔppad with T lymphocytes in vitro and found that P.gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers.Immunofluorescence staining of colon tissue paraffin sections also confirmed these results.The results suggested that P.gingivalis exacerbated the severity of UC in part via PPAD.
基金supported by grants from The National Key Research and Development Program of China (No. 2020YFC1107501)National Natural Science Foundation of China (No. 51971222)+2 种基金STS program (No. 20201600200042)Dong Guan Innovative Research Team Program, the Natural Science Foundation of Liaoning Province (2021-BS-103)the China Postdoctoral Science Foundation Grant (2020M681020)。
文摘Magnesium(Mg) alloys have attracted a wealth of attention in orthopedic fields for their superior mechanical properties, degradability,and excellent biocompatibility. Consistently, to resolve the issues on rapid degradation, more studies are dedicated to the researches on the composition design, preparation and processing, surface modification, the degradation modes of Mg alloys. Nevertheless, the mechanisms by which Mg alloys promote bone healing remain elusive. This review gives an account of specific mechanisms on Mg alloys promoting bone healing from four aspects, immunomodulatory, angiogenesis, osteogenesis and regulation of osteoclast function. We highlight the regulation of Mg alloys on the functional status and interactions of numerous cells that are involved in bone healing, including immune cells, osteogenicrelated cells, osteoclasts, endothelial cells(ECs), nerve cells, etc., and summarize the signaling pathways involved, with the aim to provide the basis and support on future investigation on mechanisms on Mg alloys driving bone regeneration. More importantly, it provides a rationale and a general new basis for the application of Mg alloys in orthopedic fields.
基金financially supported by the National Natural Science Foundation of China(Nos.U2006219,51871050 and51901039)the Natural Science Foundation of Liaoning Province(No.20180510041)+1 种基金the Liaoning Revitalization Talents Program(No.XLYC1907158)the Fundamental Research Funds for the Central Universities of the Ministry of Education of China(Nos.N180205021,N180203019,and N2002019)。
文摘In this work,microbiologically influenced corrosion(MIC)of 316 L stainless steel(SS)caused by oral microbiota was investigated with HOMINGS 16 S rRNA gene sequencing technology,and electrochemical and surface analysis techniques.The results showed that oral microbiota from different subjects developed multi-species biofilms with significant differences in structure and composition of bacteria strains on the316 L SS coupons.In the presence of oral microbiota,more severe pitting corrosion and faster dissolution of metallic ions including Ni and Cr were observed.The biofilm considerably decreased the pitting potential of 316 L SS from 1268.0±29.1 mV vs.SCE(abiotic control)to less than 500 mV vs.SCE.The corrosion current density in the presence of oral microbiota from subject 1(115.3±83.3 nA cm^(-2))and subject 2(184.4±162.0 nA cm^(-2))was at least 4 times more than that in the abiotic medium(28.0±2.3 nA cm^(-2)).The electroactive microorganisms with the potential to facilitate corrosion via extracellular electron transfer found in oral microbiota may be mainly responsible for the accelerated corrosion.
基金the study and collection,analysis,and interpretation of data were supported by the National Natural Science Foundation of China(No.51801198)the Funds of Scientific and Technological Plan of Fujian Province(Nos.2020Y9064,2020Y0083 and 2020L3026)Fujian Science&Technology Innovation Laboratory for Optoelectronic Information of China(No.2021ZZ111).
文摘Ti6Al4V3Cu alloy is a promising biomaterial for combating implant-related infection.However,the antibacterial property of Ti6Al4V3Cu is expected to be enhanced due to the low content of Cu element in titanium.To address this issue,the antibacterial property of Ti6Al4V3Cu was tailored by the grooves with different groove widths(30μm,60μm,and 90μm)that were constructed on the surface of the Ti6Al4V3Cu by selective laser melting.The effect of grooves on corrosion resistance,antibacterial property,and cytocompatibility was investigated.The electrochemical tests showed that the corrosion resistance decreased with increasing groove width.The antibacterial tests indicated that the groove with a width of 30μm and 90μm groups showed better antibacterial activity against S.aureus(>90%)compared with the groove with a width of 60μm.The in vitro study suggested that all samples with different grooves were found to exhibit good cytocompatibility with osteoblast cells.It is considered that creating grooves on Ti6Al4V3Cu by selective laser melting is a promising strategy to enhance the antibacterial activity without sacrificing cytocompatibility.
基金supported by the National Natural Science Foundation of China(No.52301091)the Medical Engineering Intersection Joint Funds of the Natural Science Foundation of Liaoning Province of China(No.2022-YGJC-01).
文摘Ti-6Al-4V(TC4)used in dentistry and orthopedics as implant biomaterial faces the risk of microbiologically influenced corrosion(MIC)owing to the residence of diverse oral microorganisms.Hereinto,Streptococcus mutans is a critical pathogenic microorganism that causes dental caries.This work investigated the corrosive effects of S.mutans on TC4 and functional gradient TC4/TC4-5Cu coupons fabricated by selective laser melting(SLM)through various electrochemical measurements,surface examination,observation of biofilm and corrosion analysis.The results indicated that the Cu-bearing alloy showed an inhibitory effect on the biofilms due to the release of Cu element,thereby reducing the corrosion rate of MIC.The corrosion current density(icorr)of TC4(11.7±0.8)nA cm−2 is higher than that of TC4/TC4-5Cu(7.4±0.4)nA cm−2 in the presence of S.mutans,while the maximum pit depth of TC4 is 1.6 times that of TC4/TC4-5Cu.Therefore,metal modification through Cu alloying is an effective strategy to improve the MIC resistance.
基金financially supported by the National Natural Science Foundation of China(No.U1737102)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.2017QNRC001)+1 种基金the Shenyang Key R&D and Technology Transfer Program(No.Z18-0-027)the Key Program of China on Biomedical Materials Research and Tissue and Organ Replacement(Nos.2016YFC1101804 and 2016YFC1100604)。
文摘Biodegradable magnesium alloys have been turned out to be a promising candidate for orthopedic applications.In this study,the mechanical properties,degradation behaviorand cytocompatibility of MgZn-Zr-Nd and Mg-Zn-Zr-Y alloys were studied in comparison with pure Mg.Mechanical tests showed that the strength and ductility of Mg-Zn-Zr-Nd and Mg-Zn-Zr-Y alloys were excellent.The corrosion resistance analyzed by electrochemical test and immersion test in alpha modified eagle(α-MEM) medium with 10% fetal bovine serum(FBS) revealed the degradation of Mg-Zn-Zr-Nd and Mg-Zn-Zr-Y alloys were faster than pure Mg at an early stage but slowed down after long time immersion.The metal ion concentrations were consistent with the corrosion rate.Mg-Zn-Zr-Nd alloy shows better mechanical properties than pure Mg and better corrosion resistance than Mg-Zn-Zr-Y alloy.The direct and indirect in vitro tests with MC3 T3-E1 cells demonstrate that Mg-Zn-Zr-Nd shows the best cytocompatibility and osteogenesis.The results suggest that Mg-Zn-Zr-Nd alloy shows an ideal combination of mechanical,corrosive and biological properties.In summary,these results implying the Mg-Zn-Zr-Nd alloy has great potential to benefit the future development of orthopedic applications.
基金the National Natural Science Foundation of China(Grant No.81870811)the Natural Science Foundation of Liaoning Province,China(Grant No.20180530082)Scientists Partner Project of China Medical University-Shenyang Branch of Chinese Academy of Sciences(Grant No.HZHB2018017).
文摘Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research.Barium titanate(BT)is an electroactive material that can generate electrical signals in response to applied mechanical forces.In this study,a BT piezoelectric ceramic coating was synthesized on the surface of a TC4 titanium alloy,forming a BT/TC4 material,and low-intensity pulsed ultrasound(LIPUS)was then applied as a mechanical stimulus.The combined effects on the biological responses of MC3T3-E1 cells were investigated.Results of scanning electron microscopy,energy-dispersive X-ray spectroscopy,and X-ray diffraction showed that an uniform nanospheres-shaped BT coating was formed on TC4 substrate.Piezoelectric behaviors were observed using piezoelectric force microscopy with the piezoelectric coefficient d_(33)of 0.42 pC/N.Electrochemical measures indicated that LIPUS-stimulated BT/TC4 materials could produce a microcurrent of approximately 10μA/cm^(2).In vitro,the greatest osteogenesis(cell adhesion,proliferation,and osteogenic differentiation)was found in MC3T3-E1 cells when BT/TC4 was stimulated using LIPUS.Furthermore,the intracellular calcium ion concentration increased in these cells,possibly because opening of the L-type calcium ion channels was promoted and expression of the Ca_(V)1.2 protein was increased.Therefore,the piezoelectric BT/TC4 material with LIPUS loading synergistically promoted osteogenesis,rending it a potential treatment for early stage formation of reliable bone-implant contact.
基金financially supported by the National Natural Science Foundation of China(No.U1737102)the Shenyang Key R&D and Technology Transfer Program(No.Z18-0-027)+1 种基金the Shenyang Science and Technology Program(No.19-112-4-029)the Fundamental Research Funds for the Central Universities(N181903009and N2002009)。
文摘Unlike other parts of the body, jaw defection often involves dental and periodontal tissues, which colonized a great many oral anaerobic bacteria. As a remarkable degradable material, magnesium has become an excellent candidate for orthopedic appliances recently. But the high degradation rate is still a big problem. Making a biodegradable coating with good biocompatibility to slow down the degeneration rate of magnesium is one of the best methods. However, protective coatings will impair the antibacterial effects of magnesium which is caused by the rise of p H value throughout its degradation. To solve this problem, a series of composite coatings with different amounts of Cu O particles(3, 5 and 7 wt.%) were fabricated on pure magnesium through plasma electrolytic oxidation(PEO) to investigate in vitro biocompatibility and the antibacterial abilities against Porphyromonas gingivalis(P. gingivalis). Surface characterization and degradation behavior of the copper-bearing PEO coatings were also systematically studied. Furthermore,the most optimum coating was also systematically studied by X-ray photoelectron spectroscopy(XPS)and electrochemical corrosion test. Results of the present research revealed that adding proper amount of Cu O into PEO coatings could greatly improve the antibacterial abilities of the PEO coatings. The antibacterial activities of copper-bearing PEO coatings were excellent and revealed concentration-dependent and time-dependent. Biocompatibility of copper-bearing PEO coatings showed that proper amount of Cu could promote cell proliferation. Compared with other PEO coatings in this study, PEO-7 Cu showed some inhibition effects on cell proliferation and adhesion for long-term use. Electrochemical corrosion tests and immersion tests showed that PEO-5 Cu and PEO-7 Cu copper-bearing PEO coatings would provide satisfying corrosion resistance effects, while PEO-3 Cu was poorer than PEO coatings without Cu. However, compared with uncoated pure magnesium, the corrosion resistance of the PEO coating was much better. Based on the results of antibacterial ability, biocompatibility, and corrosion resistance of the above copper-bearing PEO coatings, PEO-5 Cu in this research was recommended to be used in patients with jaw defects.
基金financially supported by the National Key Research and Development Program of China(Nos.2018YFC1106601 and 2016YFC1100601)the LiaoNing Revitalization Talents Program(No.XLYC1807069)+1 种基金the National Natural Science Foundation of China(Nos.51631009 and 31870954)the Key Projects for Foreign Cooperation of Bureau of International Cooperation Chinese Academy of Sciences(No.174321KYSB2018000)。
文摘In order to reduce implant-related infections and improve early osseointegration,we performed HF+anodic oxidation on the surface of the new antibacterial Ti-Cu alloy to make the titanium-based implants have a micro/submicron structure.On this basis,a series of surface-modified Ti-x Cu alloys with different Cu contents(3,5 and 7 wt%)were fabricated and a comprehensive study was conducted on MC3 T3-E1 cell adhesion,proliferation,apoptosis and its antibacterial activity against Staphylococcus aureus.Results showed that the Ti-x Cu alloys by HF etching+anodized possessed multifunctional characteristics of antibiofilm and antibacterial abilities,excellent biocompatibility and osteogenesis promoting abilities.Increment of Cu content significantly contributed to the antibacterial and osteogenic properties of HF etching+anodized Ti-Cu alloys.Cell proliferation rates of HF etching+anodized Ti-7 Cu alloys were lower than those of Ti-3 Cu and Ti-5 Cu alloys,while the early cell apoptosis rates were higher than Ti-3 Cu and Ti-5 Cu groups.All the above results finally presented that the HF etching+anodized Ti-5 Cu alloy exhibited extremely strong antibacterial properties,good biological compatibility and osteogenic ability,as well as the most excellent ductility and corrosion resistance,providing a great potential application for the future dental implantation.
基金This study was financially supported by the National Natural Science Foundation of China(No.51871050)the Natural Science Foundation Project of Liaoning Province(Nos.2020-MS-150 and 2018225059)Shenyang Science and Technology Funded Project(No.RC190290).
文摘Streptococcus mutans(S.mutans)is the most common cariogenic bacteria and causes caries by forming biofilms.A novel gradient Cu-bearing titanium alloy(TC4-5Cu/TC4)was manufactured using selective laser melting(SLM)technology for dental applications,which is anticipated to inhibit the formation of biofilm.In this study,the released concentration of copper ions in both minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)was tested in order to assess the antibacterial property of the alloy against planktonic S.mutans,and the antibacterial and antibiofilm efficiencies of TC4-5Cu/TC4 alloy against sessile S.mutans were evaluated via quantitative antibacterial tests and biofilm determination.Reverse transcription polymerase chain reaction(RT-PCR)was performed to analyze the expression of biofilm-related genes(gtfB,gtfC,gtfD,ftf and gbpB)and acid production-related gene(ldh).The results suggested that the MIC and MBC of Cu^(2+)were much higher than the release concentration of copper ions of the alloy,which was consistent with the lack of antibacterial effect against planktonic bacteria.On the contrary,TC4-5Cu/TC4 alloy exhibited significant bactericidal property against the sessile bacteria and efficient biofilm-restrained ability,and all genes detected in this research were down-regulated.The results indicated that the TC4-5Cu/TC4 alloy suppressed biofilm formation and the sessile bacterial viability by down-regulating biofilm-related genes.
基金supported by the ERC Proof-of-Concept Grant(MINGRAFT),the AO Foundation Grant(AOCMF-17-19M)the Medical Research Council(UK Regenerative Medicine Platform Acellular/Smart Materials-3D Architecture,MR/R015651/1)+2 种基金the National Natural Science Foundation of China(81870741,82001023),China Postdoctoral Science Foundation(2019M661177)Natural Science Foundation of Liaoning Province(2020-MS-154)China Scholarship Council([2020]50).
文摘The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and regeneration.Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting ability.Encapsulating or binding these biologics within biomaterials is an effective way to address these problems.Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and versatility.However,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune response.Here,we summarize how key physical and chemical properties of hydrogels affect the immune response.We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials.Then,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical cues.Thus,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.
基金financially supported by the National Key R&D Program of China(No.2020YFA0710404)the National Natural Science Foundation of China(Nos.52173269 and 51871216)+1 种基金the Liaoning Revitalization Talents Programthe Youth Innovation Promotion Association CAS。
文摘Friction and wear performance is critical for dental materials which are inevitably subject to reciprocating friction against opposing teeth in applications.Here in-vitro friction and wear behavior of bioinspired ceramic-polymer composites,which possess nacre-like lamellar and brick-and-mortar architectures and resemble human teeth in their stiffness and hardness,against human tooth enamel were quantitatively investigated to imitate actual service conditions in line with standardized testing configuration.The composites were revealed to exhibit different wear mechanisms and lead to differing extents of wear to the opposing tooth enamel depending on their specific architectural types and orientations.In particular,the brick-and-mortar architecture displayed much less wear than the lamellar one,without obviously roughening the contact surfaces with enamel owing to its high ceramic content,and as such did not accelerate the wear of enamel as compared to smooth ceramics.Such characteristics,combined with its unique stiffness and hardness matching those of human enamel as well as the good fracture toughness and machinability,endow the composite with a promising potential for dental applications.This work may provide an experimental basis to this end and may also give insights towards designing new bioinspired wear-resistant materials for reducing friction and wear.
基金supported by the National Key R&D Program of China(No.2020YFA0710404)the National Natural Science Foundation of China(Nos.51871216 and 52173269)the Youth Innovation Promotion Association CAS.
文摘Mg(and Mg alloys)and Ti(and Ti alloys)are two important classes of metallic implant materials which are respectively completely degradable and non-degradable after implantation.Making composites composed of them offers the promise for combining their property advantages for bone repair.Here,we present a Mg-Ti composite fabricated by pressureless infiltration of pure Mg melt into 3D printed Ti scaffold,and demonstrate a potential of the composite for use as new partially degradable and bioactive implant materials.The composite has such architecture that the Mg and Ti phases are topologically bicontinuous and mutually interspersed in 3D space,and exhibits several advantages over its constituents,such as higher strengths than as-cast pure Mg and Ti scaffold along with lower Young’s modulus than dense Ti.Additionally,the degradation of Mg phase may induce the formation and ingrowth of new bone tissues into the Ti scaffold to form mechanical interlocking between them;in this process,the Ti scaffold provides constant support and Young’s modulus adaptively decreases toward that of bone.Despite the accelerated corrosion than pure Mg,the composite remains non-cytotoxic and does not cause obvious adverse reactions after implantation as revealed by in vitro and in vivo experiments.This study may offer a new possibility for combining mechanical durability and bioactivity in implant materials,and allow for customized and targeted design of the implant.
基金supported by the National Key Research and Development Program of China(2021YFB3800800,2021YFC2400400)the National Natural Science Foundation of China(Nos.82022016,81991505,51973004,52103312)+1 种基金the Beijing Municipal Natural Science Foundation(7222226)Peking University Medicine Fund(PKU2020LCXQ009).
文摘Stem cells from human exfoliated deciduous teeth(SHED)uniquely exhibit high proliferative and neurogenic potential.Charged biomaterials have been demonstrated to promote neural differentiation of stem cells,but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated.Here,by utilizing different annealing temperatures prior to corona poling treatment,BaTiO_(3)/P(VDF-TrFE)ferroelectric nanocomposite membranes with varying charge polarization intensity(d_(33)≈0,4,12 and 19 pC N^(-1))were fabricated.Enhanced expression of neural markers,increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation.Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx,focal adhesion formation,FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge.Hence,this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.
