A rechargeable coating with temporal-sequence antibacterial activity and soft tissue sealing

Transcutaneous implants that penetrate through skin or mucosa are susceptible to bacteria invasion and lack proper soft tissue sealing.Traditional antibacterial strategies primarily focus on bacterial eradication,but excessive exposure to bactericidal agents can induce noticeable tissue damage.Herein,a rechargeable model(HPI-Ti)was constructed using perylene polyimide,an aqueous battery material,achieving temporal-sequence regulation of bacterial killing and soft tissue sealing.Charge storage within HPI-Ti is achieved after galvanostatic charge,and chemical discharge is initiated when immersed in physiological environments.During the early discharge stage,post-charging HPI-Ti demonstrates an antibacterial rate of 99.96±0.01%for 24 h,preventing biofilm formation.Contact-dependent violent electron transfer between bacteria and the material causes bacteria death.In the later discharge stage,the attenuated discharging status creates a gentler electron-transfer microenvironment for fibroblast proliferation.After discharge,the antibacterial activity can be reinstated by recharge against potential reinfection.The antibacterial efficacy and soft tissue compatibility were verified in vivo.These results demonstrate the potential of the charge-transfer-based model in reconciling antibacterial efficacy with tissue compatibility.

Co-implantation of magnesium and zinc ions into titanium regulates the behaviors of human gingival fibroblasts

Soft tissue sealing around implants acts as a barrier between the alveolar bone and oral environment,protecting implants from the invasion of bacteria or external stimuli.In this work,magnesium(Mg)and zinc(Zn)are introduced into titanium by plasma immersed ion implantation technology,and their effects on the behaviors of human gingival fibroblasts(HGFs)as well as the underlying mechanisms are investigated.Surface characterization confirms Mg and Zn exist on the surface in metallic and oxidized states.Contact angle test suggests that surface wettability of titanium changes after ion implantation and thus influences protein adsorption of surfaces.In vitro studies disclose that HGFs on Mg ion-implanted samples exhibit better adhesion and migration while cells on Zn ion-implanted samples have higher proliferation rate and amounts.The results of immunofluorescence staining and real-time reverse-transcriptase polymerase chain reaction(RT-PCR)suggest that Mg mainly regulates the motility and adhesion of HGFs through activating the MAPK signal pathway whereas Zn influences HGFs proliferation by triggering the TGF-βsignal pathway.The synergistic effect of Mg and Zn ions ensure that HGFs cultured on co-implanted samples possessed both high proliferation rate and motility,which are critical to soft tissue sealing of implants.

Combination types between graphene oxide and substrate affect the antibacterial activity

Duo to their superior physicochemical properties,graphene and its derivatives(GDs),such as graphene oxide(GO)and reduced graphene oxide(rGO),have attracted extensive research interests around the world.In recent years,antibacterial activities of GDs have aroused wide concern and substantial works have been done.However,the underlying antibacterial mechanisms still remain controversial.Antibacterial activities of GDs vary with various factors,such as size,number of layers,oxygen-containing groups,and experimental surroundings.We assume that combination types between graphene oxide and substrate may affect the antibacterial activity.Therefore,in this work,GO was fixed on the titanium surface with three kinds of combination types including drop with gravitational effects(GO-D),electrostatic interaction(GO-APS)and electrophoretic deposition(GO-EPD),and the antibacterial activities in vitro were systematically investigated.Results showed that combination types affected the ability of GO for preventing Staphylococcus aureus(S.aureus)from gathering,sharpness of wrinkles or edges and reactive oxygen spices(ROS)levels.Once S.aureus are in the form of separation without aggregation,GO can effectively interact with them and kill them with sharp wrinkles or edges and high ROS levels.GOEPD could effectively prevent S.aureus from gathering,own sharp wrinkles or edges and could generate higher ROS levels.As a result,GO-EPD exhibited optimal antibacterial activity against S.aureus,followed by GO-APS and GO-D.

Study of Texture Segmentation and Classification for Grading Small Hepatocellular Carcinoma Based on CT Images

To grade Small Hepatocellular Car Cinoma(SHCC)using texture analysis of CT images,we retrospectively analysed 68 cases of Grade II(medium-differentiation)and 37 cases of Grades III and IV(high-differentiation).The grading scheme follows 4 stages:(1)training a Super Resolution Generative Adversarial Network(SRGAN)migration learning model on the Lung Nodule Analysis 2016 Dataset,and employing this model to reconstruct Super Resolution Images of the SHCC Dataset(SR-SHCC)images;(2)designing a texture clustering method based on Gray-Level Co-occurrence Matrix(GLCM)to segment tumour regions,which are Regions Of Interest(ROIs),from the original and SR-SHCC images,respectively;(3)extracting texture features on the ROIs;(4)performing statistical analysis and classifications.The segmentation achieved accuracies of 0.9049 and 0.8590 in the original SHCC images and the SR-SHCC images,respectively.The classification achived an accuracy of 0.838 and an Area Under the ROC Curve(AUC)of 0.84.The grading scheme can effectively reduce poor impacts on the texture analysis of SHCC ROIs.It may play a guiding role for physicians in early diagnoses of medium-differentiation and high-differentiation in SHCC.

Synergistic effects of immunoregulation and osteoinduction of ds-block elements on titanium surface

Ds-block elements have been gaining increasing attention in the field of biomaterials modification,owing to their excellent biological properties,such as antibiosis,osteogenesis,etc.However,their function mechanisms are not well understood and conflicting conclusions were drawn by previous studies on this issue,which are mainly resulted from the inconsistent experimental conditions.In this work,three most widely used ds-block elements,copper,zinc,and silver were introduced on titanium substrate by plasma immersion ion implantation method to investigate the rule of ds-block elements in the immune responses.Results showed that the implanted samples could decrease the inflammatory responses compared with Ti sample.The trend of anti-inflammatory effects of macrophages on samples was in correlation with cellular ROS levels,which was induced by the implanted biomaterials and positively correlated with the number of valence electrons of ds-block elements.The co-culture experiments of macrophages and bone marrow mesenchymal stem cells showed that these two kinds of cells could enhance the anti-inflammation and osteogenesis of samples by the paracrine manner of PGE2.In general,in their steady states on titanium substrate(Cu2+,Zn2+,Ag),the ds-block elements with more valence electrons exhibit better anti-inflammatory and osteogenic effects.Moreover,molecular biology experiments indicate that the PGE2-related signaling pathway may contribute to the desired immunoregulation and osteoinduction capability of ds-block elements.These findings suggest a correlation between the number of valence electrons of ds-block elements and the relevant biological responses,which provides new insight into the selection of implanted ions and surface design of biomaterials.

FeeNeC single atom nanozymes with dual enzyme-mimicking activities for colorimetric detection of hydrogen peroxide and glutathione

H_(2)O_(2) and glutathione(GSH)are critical redox molecules in the organism.Abnormal levels of cellular H_(2)O_(2) and GSH are closely related to some diseases.Thus,it is imperative to detect H_(2)O_(2) and GSH effi-ciently.In this work,FeeNeC single atom nanozymes(SANs)with both peroxidase and oxidasemimicking activities were successfully prepared with the help of formamide condensation by one-step hydrothermal method.The FeeNeC SANs show excellent peroxidase-like activity,which possess a higher affinity for H_(2)O_(2) and 3,30,5,50-tetramethylbenzidine(TMB)than horseradish peroxidase(HRP).Then,based on the chromogenic reaction of TMB,a colorimetric biosensor to detect H_(2)O_(2) and GSH was developed.This biosensor has the linear ranges of 10-600 mmol/L for H_(2)O_(2) with a low detection limit of 4.360 mmol/L and 100-400 mmol/L for GSH with a low detection limit of 78.33 mmol/L.Besides,this colorimetric biosensor exhibited a good recovery of H_(2)O_(2) and GSH in diluted human serum.Finally,the FeeNeC SANs were encapsulated into agar gel to self-quantitatively detect GSH by naked eyes.This work provides a non-pyrolytic way to prepare SANs,which broadens the synthetic method of SANs and may promote the development of SANs for biosensor application.

An injectable hydrogel combining medicine and matrix with anti-inflammatory and pro-angiogenic properties for potential treatment of myocardial infarction

One of the main illnesses that put people’s health in jeopardy is myocardial infarction(MI).After MI,damaged or dead cells set off an initial inflammatory response that thins the ventricle wall and degrades the extracellular matrix.At the same time,the ischemia and hypoxic conditions resulting from MI lead to significant capillary obstruction and rupture,impairing cardiac function and reducing blood flow to the heart.Therefore,attenuating the initial inflammatory response and promoting angiogenesis are very important for the treatment of MI.Here,to reduce inflammation and promote angiogenesis in infarcted area,we report a new kind of injectable hydrogel composed of puerarin and chitosan via in situ self-assembly with simultaneous delivery of mesoporous silica nanoparticles(CHP@Si)for myocardial repair.On the one hand,puerarin degraded from CHP@Si hydrogel modulated the inflammatory response via inhibiting M1-type polarization of macrophages and expression of pro-inflammatory factors.On the other hand,silica ions and puerarin released from CHP@Si hydrogel showed synergistic activity to improve the cell viability,migration and angiogenic gene expression of HUVECs in both conventional and oxygen/glucose-deprived environments.It suggests that this multifunctional injectable CHP@Si hydrogel with good biocompatibility may be an appropriate candidate as a bioactive material for myocardial repair post-MI.

Defect engineering endows NiTi stents with photothermal-enhanced catalytic activity for high-efficiency tumor therapy

NiTi stents are widely used in clinic for palliative care to relieve obstruction caused by Gastrointestinal(GI)cancers,which have high morbidity and mortality rates.However,tumor invasion and tumor overgrowth around the stent after surgery may lead to re-obstruction of the lumen.Thus,it is urgent to endow NiTi stents with excellent tumor suppressive ability and good biocompatibility.In this study,Ce-BTC was firstly prepared on the surface of NiTi pretreated by alkaline heat,followed by pyrolysis in Ar atmosphere at 450℃.Then,a composite coating consisting of defective cerium oxide and black Ni-Ti hydroxide/oxide was constructed on NiTi surface,which exhibited tumor microenvironment-response and hyperthermia-enhanced catalytic ability.Under near-infrared light irradiation,the photothermal performance of black Ni-Ti hydroxide/oxide and hyperthermia-enhanced catalytic activity of defective cerium oxide can achieve a synergistic effect of photothermal therapy and tumor catalytic therapy.Thereafter,defective cerium oxide can sustainably inhibit the proliferation of residual tumor cells by the generation of reactive oxygen species.Moreover,the composite coating has no obvious cytotoxicity to normal cells.This work provides a new insight for the preparation of stimulus-responsive antitumor stents for palliative treatment of gastrointestinal cancer.

Characteristics ofβ-type Ti-41Nb alloy produced by laser powder bed fusion:Microstructure,mechanical properties and in vitro biocompatibility

Aβ-type Ti-41 Nb alloy with high relative density has been successfully fabricated by laser powder bed fusion(L-PBF)using pre-alloyed powders for potential implant application.The homogeneous microstructure can be achieved in L-PBF fabricated(L-PBFed)Ti-41 Nb alloy but slight composition segregation was detected along molten pool boundaries.The L-PBFed alloy was dominated by typical epitaxial columnar grains with strong(001)grain orientation along building direction(BD),and cellular structure was distinguished within the columnar grains.The main reasons for this microstructure can be attributed to effective thermal gradient and epitaxial growth.L-PBFed alloy exhibited higher mechanical strength compared with cold rolling plus annealing(CRA)alloy due to the finer grains,dislocations accumulation and different TRIP behaviors,accompanied by good ductility.It also exhibited much lower thermal conductivity and better hydrophilic feature than those of CP-Ti.Besides,the L-PBFed alloy exhibited slightly better cell spread and cell proliferation rates compared with CP-Ti.Moreover,L-PBFed alloy presented better alkaline phosphatase(ALP)activities and extracellular matrix(ECM)mineralization,which suggests that the L-PBFed alloy can stimulate the osteogenic differentiation of rat bone mesenchymal stem cells.The Ti-41 Nb alloy,fabricated by L-PBF,reveals a good combination of mechanical properties,physicochemical properties and biocompatibility,exhibiting the great potential as the dental implant.

Why does nitrogen-doped graphene oxide lose the antibacterial activity?

Graphene and its derivatives attract extensive research interests in the biomedicine field due to their outstanding physiochemical properties.Lots of studies have reported that graphene materials exhibit antibacterial activities.However,antibacterial mechanisms of graphene materials still remain controversial and need further investigation.Herein,graphene oxide(GO)with and without nitrogen-doping were fabricated on the titanium surface by cathodic electro phoretic deposition and antibacterial activities were systematically investigated.Results showed that GO on the titanium surface presented antibacterial activity,while nitrogen-doped GO lost the antibacterial activity.The reason is that antibacterial mechanisms for the GO-metal system contain two steps.First,electron transfer occurs from bacterium's cell membrane to GO surface which destroys the bacterial respiratory chain;subsequently,electrons on GO surface induce the production of reactive oxygen species(ROS)that damage the membrane structure and eventually lead to bacterial death.For nitrogen-doped GO,nitrogen atoms denote electrons into GO leading to n-type doping.Nitrogen-doped GO as an electron donor cuts off the electron transfer from the cell membrane to GO and subsequently inhibits the production of ROS.This is why nitrogen-doped GO exhibits no antibacterial activity.This work confirms the antibacterial mecha nisms for the GO-metal system with a synergistic effect of non-oxidative electron transfer and ROS mediated oxidative stress.