The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defec...The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.展开更多
Background:Soil organic carbon(SOC)is important for soil quality and fertility in forest ecosystems.Labile SOC fractions are sensitive to environmental changes,which reflect the impact of short-term internal and exter...Background:Soil organic carbon(SOC)is important for soil quality and fertility in forest ecosystems.Labile SOC fractions are sensitive to environmental changes,which reflect the impact of short-term internal and external management measures on the soil carbon pool.Organic mulching(OM)alters the soil environment and promotes plant growth.However,little is known about the responses of SOC fractions in rhizosphere or bulk soil to OM in urban forests and its correlation with carbon composition in plants.Methods:A one-year field experiment with four treatments(OM at 0,5,10,and 20 cm thicknesses)was conducted in a 15-year-old Ligustrum lucidum plantation.Changes in the SOC fractions in the rhizosphere and bulk soil;the carbon content in the plant fine roots,leaves,and organic mulch;and several soil physicochemical properties were measured.The relationships between SOC fractions and the measured variables were analysed.Results:The OM treatments had no significant effect on the SOC fractions,except for the dissolved organic carbon(DOC).OM promoted the movement of SOC to deeper soil because of the increased carbon content in fine roots of subsoil.There were significant correlations between DOC and microbial biomass carbon and SOC and easily oxidised organic carbon.The OM had a greater effect on organic carbon fractions in the bulk soil than in the rhizosphere.The thinnest(5 cm)mulching layers showed the most rapid carbon decomposition over time.The time after OM had the greatest effect on the SOC fractions,followed by soil layer.Conclusions:The frequent addition of small amounts of organic mulch increased SOC accumulation in the present study.OM is a potential management model to enhance soil organic matter storage for maintaining urban forest productivity.展开更多
The static comer frequency and dynamic comer frequency in stochastic synthesis of ground motion from fi- nite-fault modeling are introduced, and conceptual disadvantages of the two are discussed in this paper. Further...The static comer frequency and dynamic comer frequency in stochastic synthesis of ground motion from fi- nite-fault modeling are introduced, and conceptual disadvantages of the two are discussed in this paper. Furthermore, the non-uniform radiation of seismic wave on the fault plane, as well as the trend of the larger rupture area, the lower comer frequency, can be described by the source spectral model developed by the authors. A new dynamic comer frequency can be developed directly from the model. The dependence of ground motion on the size of subfault can be eliminated if this source spectral model is adopted in the synthesis. Finally, the approach presented is validated from the comparison between the synthesized and observed ground motions at six rock stations during the Northridge earthquake in 1994.展开更多
Nitrogen is an essential component in forest ecosystem nutrient cycling.Nitrogen fractions,such as dissolved nitrogen,ammonium,nitrate,and microbial biomass nitrogen,are sensitive indicators of soil nitrogen pools whi...Nitrogen is an essential component in forest ecosystem nutrient cycling.Nitrogen fractions,such as dissolved nitrogen,ammonium,nitrate,and microbial biomass nitrogen,are sensitive indicators of soil nitrogen pools which affect soil fertility and nutrient cycling.However,the responses of nitrogen fractions in forest soils to organic mulching are less well understood.The rhizosphere is an important micro-region that must be considered to better understand element cycling between plants and the soil.A field investigation was carried out on the effect of mulching soil in a 15-year-old Ligustrum lucidum urban plantation.Changes in total nitrogen and nitrogen fractions in rhizosphere and bulk soil in the topsoil(upper 20 cm)and in the subsoil(20-40 cm)were evaluated following different levels of mulching,in addition to nitrogen contents in fine roots,leaves,and organic mulch.The relationships between nitrogen fractions and other measured variables were analysed.Organic mulching had no significant effect on most nitrogen fractions except for the rhizosphere microbial biomass nitrogen(MBN),and the thinnest(5 cm)mulching layer showed greater effects than other treatments.Rhizosphere MBN was more sensitive to mulching compared to bulk soil,and was more affected by soil environmental changes.Season and soil depth had more pronounced effects on nitrogen fractions than mulching.Total nitrogen and dissolved nitrogen were correlated to soil phosphorus,whereas other nitrogen fractions were strongly affected by soil physical properties(temperature,water content,bulk density).Mulching also decreased leaf nitrogen content,which was more related to soil nitrogen fractions(except for MBN)than nitrogen contents in either fine roots or organic mulch.Frequent applications of small quantities of organic mulch contribute to nitrogen transformation and utilization in urban forests.展开更多
The Palongzangbu River Basin contains the highest number of maritime province glaciers in China. There are 130 glacial lakes, 64 snow avalanche sites and 28 glacial debris flow gullies distributed within the basin. Sn...The Palongzangbu River Basin contains the highest number of maritime province glaciers in China. There are 130 glacial lakes, 64 snow avalanche sites and 28 glacial debris flow gullies distributed within the basin. Snow disasters play a controlling role in the Sichuan-Tibet Highway construction, due to the terrain’s special characteristics of high altitude and large height differential. Segmentation mitigation countermeasures for the Sichuan-Tibet Highway are presented based on snow disaster severity level and damage mode of the road. In the Ranwu to Midui section, snow avalanches are regional disasters, so the line should be placed in sunny slopes. In the Midui Gully to Yupu section, the line should be placed in shady slopes and at higher elevations to reduce the risk of glacial lake outburst. In the Yupu to Guxiang section, all three snow disasters are minimal. In the Guxiang to Tongmai section, glacier debris flows are the major threat, thus the road should be placed in shady slopes.展开更多
Stochastic modeling of ground motion is a simple tool to predict ground shaking level for future earthquake and less time consuming than physics-based deterministic modeling.In this paper,a record-based stochastic met...Stochastic modeling of ground motion is a simple tool to predict ground shaking level for future earthquake and less time consuming than physics-based deterministic modeling.In this paper,a record-based stochastic method that considers the time-and frequency-evolution of ground motion is used to estimate ground motion for scenario earthquakes in tectonic active region.The stochastic method employs a time-domain modulation function to describe the temporal nonstationarity and a filter impulse response function that describe the evolution of frequency content.For characterizing the modulation function and the filter impulse function,six parameters(Ia,D5-95,tmid,ωmid,ω',ξf)are defined,and 2,571 pairs of ground motion recording in the NGA-west2 database are selected to identify the six parameters.Probabilistic density function is assigned to each of the parameter by fitting the frequency distribution histogram.The parameters are then transformed into standard normal space where regression analysis is performed by considering each parameter as function of moment magnitude,rupture distance,vS30(The time-averaged shear wave velocity of the top 30 m of soil).The prediction equations are used to generate ground motions for several scenario earthquakes and compared to NGA-West2 GMPEs.展开更多
Purpose–The smoothness of the high-speed railway(HSR)on the bridge may exceed the allowable standard when an earthquake causes vibrations for HSR bridges,which may threaten the safety of running trains.Indeed,few stu...Purpose–The smoothness of the high-speed railway(HSR)on the bridge may exceed the allowable standard when an earthquake causes vibrations for HSR bridges,which may threaten the safety of running trains.Indeed,few studies have evaluated the exceeding probability of rail displacement exceeding the allowable standard.The purposes of this article are to provide a method for investigating the exceeding probability of the rail displacement of HSRs under seismic excitation and to calculate the exceeding probability.Design/methodology/approach–In order to investigate the exceeding probability of the rail displacement under different seismic excitations,the workflow of analyzing the smoothness of the rail based on incremental dynamic analysis(IDA)is proposed,and the intensity measure and limit state for the exceeding probability analysis of HSRs are defined.Then a finite element model(FEM)of an assumed HSR track-bridge system is constructed,which comprises a five-span simply-supported girder bridge supporting a finite length CRTS II ballastless track.Under different seismic excitations,the seismic displacement response of the rail is calculated;the character of the rail displacement is analyzed;and the exceeding probability of the rail vertical displacement exceeding the allowable standard(2mm)is investigated.Findings–The results show that:(1)The bridge-abutment joint position may form a step-like under seismic excitation,threatening the running safety of high-speed trains under seismic excitations,and the rail displacements at mid-span positions are bigger than that at other positions on the bridge.(2)The exceeding probability of rail displacement is up to about 44%when PGA 50.01g,which is the level-five risk probability and can be described as’very likely to happen’.(3)The exceeding probability of the rail at the mid-span positions is bigger than that above other positions of the bridge,and the mid-span positions of the track-bridge system above the bridge may be the most hazardous area for the running safety of trains under seismic excitation when high-speed trains run on bridges.Originality/value–The work extends the seismic hazardous analysis of HSRs and would lead to a better understanding of the exceeding probability for the rail of HSRs under seismic excitations and better references for the alert of the HSR operation.展开更多
Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments.The physical signals of structural anisotropy o...Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments.The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through physical contact and cellular mechano-sensing pathways,irrespective of cell type.In this study,we developed a highly oriented anisotropic nanofiber hydrogel designed to provide directional guidance for cellular extension and cytoskeletal organization,thereby achieving pronounced multicellular modulation,including shape-induced polarization of macrophages,morphogenetic maturation of Schwann cells,oriented extracellular matrix(ECM)deposition by fibroblasts,and enhanced vascularization by endothelial cells.Additionally,we incorporated a VEGF-mimicking peptide to further reinforce angiogenesis,a pivotal phase that interlocks with immune regulation,neurogenesis,and tissue regeneration,ultimately contributing to optimized inter-microenvironmental crosstalk.In vivo studies validated that the anisotropic bioactive nanofiber hydrogel effectively accelerated diabetic wound healing by harnessing the triadic synergy of the immune-angiogenic-neurogenic microenvironments.Our findings highlight the promising potential of combining physical and bioactive signals for the modulation of various cell types and the refinement of the multidimensional microenvironment,offering a novel strategy for diabetic wound healing.展开更多
Biomimetic neural substitutes,constructed through the bottom-up assembly of cell-matrix modulus via 3D bioprinting,hold great promise for neural regeneration.However,achieving precise control over the fate of neural s...Biomimetic neural substitutes,constructed through the bottom-up assembly of cell-matrix modulus via 3D bioprinting,hold great promise for neural regeneration.However,achieving precise control over the fate of neural stem cells(NSCs)to ensure biological functionality remains challenging.Cell behaviors are closely linked to cellular dynamics and cell-matrix mechanotransduction within a 3D microenvironment.To address this,a dynamic bioactive bioink is designed to provide adaptable biomechanics and instructive biochemical cues,specifically tailored for the fate commitment of NSCs,through incorporating reversible Schiff-base bonds and bioactive motifs,N-cadherin-mimicking and BDNF-mimicking peptides.We demonstrate that the dynamic properties of 3D bioprinted living fibers alleviate the mechanical confinement on NSCs and significantly enhance their mechanosensing,spreading,migration,and matrix remodeling within the 3D matrix.Additionally,the inclusion of N-cadherin-mimicking and BDNF-mimicking peptides further enhances cells’ability to sense and respond to mechanical and neurotrophic cues provided by the surrounding matrix,which accelerates the selforganization of a functional neural network within the 3D bioprinted construct,leading to significant motor and sensory function recovery in a rat complete spinal cord injury model.This work underscores the critical role of precisely designing cell-instructive bioinks for the advanced functionality of 3D bioprinted living constructs in neural regeneration.展开更多
Bone marrow(BM),a natural niche rich in growth factors and bone marrow mesenchymal stem cells(BMSCs),provides an optimal regenerative microenvironment and is widely used in clinical applications.However,the limited pr...Bone marrow(BM),a natural niche rich in growth factors and bone marrow mesenchymal stem cells(BMSCs),provides an optimal regenerative microenvironment and is widely used in clinical applications.However,the limited proliferative capacity of BMSCs and the mismatch between bone regeneration and growth factors release constrain their effectiveness in treating critical bone defects.Drawing inspiration from the regenerative properties of BM,we developed self-assembled hybrid microspheres to replicate its function and address these challenges through a tissue engineering approach.This BM-mimicking niche enriched BMSCs via fast-degrading gelatin methacryloyl(GelMA)microspheres,which were loaded with exogenous BMSCs and conjugated with stem cell homing peptides(SKP)to recruit endogenous BMSCs.SKP further enhanced the stemness of BMSCs,thereby promoting angiogenesis and resolving inflammation.Slow-degrading chitosan methacryloyl(ChitoMA)microspheres facilitated sustained release of angiogenic(KLT)and osteogenic(OGP)peptides,supporting blood vessel maturation and osteogenesis.The early release of BMSCs and SKP,followed by the subsequent release of OGP and KLT,aligned with the dynamic process of bone regeneration.In a rat critical femoral condyle defect model,the BM-mimicking niche formed an in-situ ossification center,significantly enhancing bone regeneration.This study introduces a novel BM-mimicking niche characterized by a BMSC-enriched environment and the sequential release of therapeutic factors,offering a promising strategy for treating critical bone defects.展开更多
Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging...Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging （MRI）-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes （IOMS NCs） via the integration of MoS2 （MS） film onto iron oxide （IO） nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose （2-DG）, a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs （IOMS-PEG-2DG NCs） acted as drug-carriers for doxorubicin （DOX）, which could be easily loaded within the NCs. The obtained IOMS-PEG（DOX）-2DG NCs exhibited a 3？2 relaxivity coefficient of 48.86 （mM）^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG（DOX）-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.展开更多
Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment u...Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube （hCST） to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide （RGI, RGIDKRHWNSQ） derived from brain-derived neurotrophic factor （BDNF） to the C-terminus of the self-assembling peptide RADA16-I （Ac-（RADA）4-CONH2）. Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.展开更多
Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expect...Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.展开更多
Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of deve...Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.展开更多
Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles （NPs） as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential t...Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles （NPs） as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential toxicity in synthesis, the lack of general methods for the controlled synthesis of various kinds of magnetic NP （MNP）@conjugated polymer NPs, and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics. We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole （PPy） NPs with balanced, prominent magneto-optical properties. MNP@PPy NPs with an adjustable size, different shapes, and a controlled shell thickness were obtained using this method. The method was extended to synthesize other MNP-conjugated polymer core-shell NPs, such as MNP@polyaniline and MNP@poly（3,4-ethylenedioxythiophene）：poly（4- styrenesulfonate） （PEDOT：PSS）. We discuss the formation mechanism of the proposed method according to our experimental results. Finally, using the optical and magnetic properties of the obtained MNP@PEDOT：PSS NPs, in vivo multimodal imaging-guided hyperthermia was induced in mice, achieving an excellent tumor-ablation therapeutic effect. Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.展开更多
Adult central nervous system （CNS） tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterial- loaded stem cells with the capability of differentiation ...Adult central nervous system （CNS） tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterial- loaded stem cells with the capability of differentiation to specific neural population has directed focuses toward the recovery of CNS. Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal cells. Here we report on the fabrication of an electrospun polypyrrole/polylactide composite nanofiber film that direct or determine the fate of mesenchymal stem cells （MSCs）, via combination of aligned surface topography, and electrical stimulation （ES）. The surface morphology, mechanical properties and electric properties of the film were characterized. Comparing with that on random surface film, expression of neurofilament-lowest and nestin of human umbilical cord mesenchymal stem cells （huMSCs） cultured on film with aligned surface topography and ES were obviously enhanced. These results suggest that aligned topography combining with ES facilitates the neurogenic differentiation of huMSCs and the aligned conductive film can act as a potential nerve scaffold.展开更多
The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained in...The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.展开更多
The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which e...The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.展开更多
The induction time of cefodizime sodium was measured in ethanol-water at different solvent composi- tions by the laser technology measurement. The results indicate that the solvent composition played an important role...The induction time of cefodizime sodium was measured in ethanol-water at different solvent composi- tions by the laser technology measurement. The results indicate that the solvent composition played an important role in the supersaturation and the nucleation process of cefodizime sodium solution. According to the modified classical nucleation theory, the nucleation and growth mechanism were identified. The correlation results show that heterogeneous nucleation dominated the nucleation process at lower supersaturation, where homogeneous nucleation is the most important mechanism at higher supersaturation. Based on the correlated results, the 2D mediated growth mechanism had the highest correlation coefficients （R2）, so this mechanism was selected as the proper growth mechanism for cefodizime sodium.展开更多
A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical prop...A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical properties and in vitro degradation behavior were all evaluated.The adhesion and proliferation of Schwann cells(SCs)were observed.In the in vivo experiment,MC@Col NGC and other conduits including Col,chitosan(CST)and polycaprolactone(PCL)conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect.Histological analyses,morphological analyses,electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks.The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC.In vitro cytocompatibility evaluation revealed that the SCs had good viability,attachment and proliferation in the MC@Col.In in vivo results,the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects,but superior to those by Col,CST and PCL conduits.The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration,thus showing great promising potential as a new type of conduit in clinical applications.展开更多
基金financially supported by the Versus Arthritis (No. 21160)the Rosetree Trust (No. A1184)+2 种基金the European Commission via H2020-MSCA-RISE Program (BAMOS Project (No.734156))Innovate UK via Newton Fund (No. 102872)the Engineering and Physical Science Research Council (EPSRC) via DTP Case Programme (No. EP/T517793/1)
文摘The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.
基金This work was supported by the National Key Research and Development Program of China(No.2016YFC0502703)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Postgraduate Research&Practice Innovation Program of Jiangsu Province.
文摘Background:Soil organic carbon(SOC)is important for soil quality and fertility in forest ecosystems.Labile SOC fractions are sensitive to environmental changes,which reflect the impact of short-term internal and external management measures on the soil carbon pool.Organic mulching(OM)alters the soil environment and promotes plant growth.However,little is known about the responses of SOC fractions in rhizosphere or bulk soil to OM in urban forests and its correlation with carbon composition in plants.Methods:A one-year field experiment with four treatments(OM at 0,5,10,and 20 cm thicknesses)was conducted in a 15-year-old Ligustrum lucidum plantation.Changes in the SOC fractions in the rhizosphere and bulk soil;the carbon content in the plant fine roots,leaves,and organic mulch;and several soil physicochemical properties were measured.The relationships between SOC fractions and the measured variables were analysed.Results:The OM treatments had no significant effect on the SOC fractions,except for the dissolved organic carbon(DOC).OM promoted the movement of SOC to deeper soil because of the increased carbon content in fine roots of subsoil.There were significant correlations between DOC and microbial biomass carbon and SOC and easily oxidised organic carbon.The OM had a greater effect on organic carbon fractions in the bulk soil than in the rhizosphere.The thinnest(5 cm)mulching layers showed the most rapid carbon decomposition over time.The time after OM had the greatest effect on the SOC fractions,followed by soil layer.Conclusions:The frequent addition of small amounts of organic mulch increased SOC accumulation in the present study.OM is a potential management model to enhance soil organic matter storage for maintaining urban forest productivity.
基金supported by National Natural Science Foundation of China under grant No. 50778058 and 90715038National Key Technology Research and Development Program under grant No. 2006BAC13B02
文摘The static comer frequency and dynamic comer frequency in stochastic synthesis of ground motion from fi- nite-fault modeling are introduced, and conceptual disadvantages of the two are discussed in this paper. Furthermore, the non-uniform radiation of seismic wave on the fault plane, as well as the trend of the larger rupture area, the lower comer frequency, can be described by the source spectral model developed by the authors. A new dynamic comer frequency can be developed directly from the model. The dependence of ground motion on the size of subfault can be eliminated if this source spectral model is adopted in the synthesis. Finally, the approach presented is validated from the comparison between the synthesized and observed ground motions at six rock stations during the Northridge earthquake in 1994.
基金This study was supported by the National Natural Science Foundation of China(No.31971453)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)and Postgraduate Research&Practice Innovation Program of Jiangsu Province.
文摘Nitrogen is an essential component in forest ecosystem nutrient cycling.Nitrogen fractions,such as dissolved nitrogen,ammonium,nitrate,and microbial biomass nitrogen,are sensitive indicators of soil nitrogen pools which affect soil fertility and nutrient cycling.However,the responses of nitrogen fractions in forest soils to organic mulching are less well understood.The rhizosphere is an important micro-region that must be considered to better understand element cycling between plants and the soil.A field investigation was carried out on the effect of mulching soil in a 15-year-old Ligustrum lucidum urban plantation.Changes in total nitrogen and nitrogen fractions in rhizosphere and bulk soil in the topsoil(upper 20 cm)and in the subsoil(20-40 cm)were evaluated following different levels of mulching,in addition to nitrogen contents in fine roots,leaves,and organic mulch.The relationships between nitrogen fractions and other measured variables were analysed.Organic mulching had no significant effect on most nitrogen fractions except for the rhizosphere microbial biomass nitrogen(MBN),and the thinnest(5 cm)mulching layer showed greater effects than other treatments.Rhizosphere MBN was more sensitive to mulching compared to bulk soil,and was more affected by soil environmental changes.Season and soil depth had more pronounced effects on nitrogen fractions than mulching.Total nitrogen and dissolved nitrogen were correlated to soil phosphorus,whereas other nitrogen fractions were strongly affected by soil physical properties(temperature,water content,bulk density).Mulching also decreased leaf nitrogen content,which was more related to soil nitrogen fractions(except for MBN)than nitrogen contents in either fine roots or organic mulch.Frequent applications of small quantities of organic mulch contribute to nitrogen transformation and utilization in urban forests.
基金financially supported by the general project of Natural Science Foundation of China (No. 41571004)Scientific and technological research and development plan of China Railway Corporation (No. 2015G002-N)General project of Natural Science Foundation of China (No. 41172321)
文摘The Palongzangbu River Basin contains the highest number of maritime province glaciers in China. There are 130 glacial lakes, 64 snow avalanche sites and 28 glacial debris flow gullies distributed within the basin. Snow disasters play a controlling role in the Sichuan-Tibet Highway construction, due to the terrain’s special characteristics of high altitude and large height differential. Segmentation mitigation countermeasures for the Sichuan-Tibet Highway are presented based on snow disaster severity level and damage mode of the road. In the Ranwu to Midui section, snow avalanches are regional disasters, so the line should be placed in sunny slopes. In the Midui Gully to Yupu section, the line should be placed in shady slopes and at higher elevations to reduce the risk of glacial lake outburst. In the Yupu to Guxiang section, all three snow disasters are minimal. In the Guxiang to Tongmai section, glacier debris flows are the major threat, thus the road should be placed in shady slopes.
基金supported by the National Natural Science Foundation of China(No.51878578).
文摘Stochastic modeling of ground motion is a simple tool to predict ground shaking level for future earthquake and less time consuming than physics-based deterministic modeling.In this paper,a record-based stochastic method that considers the time-and frequency-evolution of ground motion is used to estimate ground motion for scenario earthquakes in tectonic active region.The stochastic method employs a time-domain modulation function to describe the temporal nonstationarity and a filter impulse response function that describe the evolution of frequency content.For characterizing the modulation function and the filter impulse function,six parameters(Ia,D5-95,tmid,ωmid,ω',ξf)are defined,and 2,571 pairs of ground motion recording in the NGA-west2 database are selected to identify the six parameters.Probabilistic density function is assigned to each of the parameter by fitting the frequency distribution histogram.The parameters are then transformed into standard normal space where regression analysis is performed by considering each parameter as function of moment magnitude,rupture distance,vS30(The time-averaged shear wave velocity of the top 30 m of soil).The prediction equations are used to generate ground motions for several scenario earthquakes and compared to NGA-West2 GMPEs.
基金supported by National Key Research and Development Plan of China“Basic Theory and Methods for Resilience Assessment and Risk Control of Transportation Infrastructures”(2021YFB2600500)the National Nature Science Foundation of Si Chuan(2023NSFSC0388)the Joint Research Fund for Earthquake Science launched by the National Natural Science Foundation of China and China Earthquake Administration(U2039208).
文摘Purpose–The smoothness of the high-speed railway(HSR)on the bridge may exceed the allowable standard when an earthquake causes vibrations for HSR bridges,which may threaten the safety of running trains.Indeed,few studies have evaluated the exceeding probability of rail displacement exceeding the allowable standard.The purposes of this article are to provide a method for investigating the exceeding probability of the rail displacement of HSRs under seismic excitation and to calculate the exceeding probability.Design/methodology/approach–In order to investigate the exceeding probability of the rail displacement under different seismic excitations,the workflow of analyzing the smoothness of the rail based on incremental dynamic analysis(IDA)is proposed,and the intensity measure and limit state for the exceeding probability analysis of HSRs are defined.Then a finite element model(FEM)of an assumed HSR track-bridge system is constructed,which comprises a five-span simply-supported girder bridge supporting a finite length CRTS II ballastless track.Under different seismic excitations,the seismic displacement response of the rail is calculated;the character of the rail displacement is analyzed;and the exceeding probability of the rail vertical displacement exceeding the allowable standard(2mm)is investigated.Findings–The results show that:(1)The bridge-abutment joint position may form a step-like under seismic excitation,threatening the running safety of high-speed trains under seismic excitations,and the rail displacements at mid-span positions are bigger than that at other positions on the bridge.(2)The exceeding probability of rail displacement is up to about 44%when PGA 50.01g,which is the level-five risk probability and can be described as’very likely to happen’.(3)The exceeding probability of the rail at the mid-span positions is bigger than that above other positions of the bridge,and the mid-span positions of the track-bridge system above the bridge may be the most hazardous area for the running safety of trains under seismic excitation when high-speed trains run on bridges.Originality/value–The work extends the seismic hazardous analysis of HSRs and would lead to a better understanding of the exceeding probability for the rail of HSRs under seismic excitations and better references for the alert of the HSR operation.
基金financial support from the Beijing Natural Science Foundation of China(Grant No.QY23102,2254091,and L234075)the National Natural Science Foundation of China(Grant No.32271414,32401140,and 82301560).
文摘Wound healing in chronic diabetic patients remains challenging due to the multiple types of cellular dysfunction and the impairment of multidimensional microenvironments.The physical signals of structural anisotropy offer significant potential for orchestrating multicellular regulation through physical contact and cellular mechano-sensing pathways,irrespective of cell type.In this study,we developed a highly oriented anisotropic nanofiber hydrogel designed to provide directional guidance for cellular extension and cytoskeletal organization,thereby achieving pronounced multicellular modulation,including shape-induced polarization of macrophages,morphogenetic maturation of Schwann cells,oriented extracellular matrix(ECM)deposition by fibroblasts,and enhanced vascularization by endothelial cells.Additionally,we incorporated a VEGF-mimicking peptide to further reinforce angiogenesis,a pivotal phase that interlocks with immune regulation,neurogenesis,and tissue regeneration,ultimately contributing to optimized inter-microenvironmental crosstalk.In vivo studies validated that the anisotropic bioactive nanofiber hydrogel effectively accelerated diabetic wound healing by harnessing the triadic synergy of the immune-angiogenic-neurogenic microenvironments.Our findings highlight the promising potential of combining physical and bioactive signals for the modulation of various cell types and the refinement of the multidimensional microenvironment,offering a novel strategy for diabetic wound healing.
基金support from the National Natural Science Foundation of China(Grant No.32271414 and 82301560)support from State Key Laboratory of New Ceramic Materials Tsinghua University(No.KF202409).
文摘Biomimetic neural substitutes,constructed through the bottom-up assembly of cell-matrix modulus via 3D bioprinting,hold great promise for neural regeneration.However,achieving precise control over the fate of neural stem cells(NSCs)to ensure biological functionality remains challenging.Cell behaviors are closely linked to cellular dynamics and cell-matrix mechanotransduction within a 3D microenvironment.To address this,a dynamic bioactive bioink is designed to provide adaptable biomechanics and instructive biochemical cues,specifically tailored for the fate commitment of NSCs,through incorporating reversible Schiff-base bonds and bioactive motifs,N-cadherin-mimicking and BDNF-mimicking peptides.We demonstrate that the dynamic properties of 3D bioprinted living fibers alleviate the mechanical confinement on NSCs and significantly enhance their mechanosensing,spreading,migration,and matrix remodeling within the 3D matrix.Additionally,the inclusion of N-cadherin-mimicking and BDNF-mimicking peptides further enhances cells’ability to sense and respond to mechanical and neurotrophic cues provided by the surrounding matrix,which accelerates the selforganization of a functional neural network within the 3D bioprinted construct,leading to significant motor and sensory function recovery in a rat complete spinal cord injury model.This work underscores the critical role of precisely designing cell-instructive bioinks for the advanced functionality of 3D bioprinted living constructs in neural regeneration.
基金funding support from the Beijing Science and Technology Project(Z241100009324005)National Key Research and Development Program of China(2023YFC2412302).
文摘Bone marrow(BM),a natural niche rich in growth factors and bone marrow mesenchymal stem cells(BMSCs),provides an optimal regenerative microenvironment and is widely used in clinical applications.However,the limited proliferative capacity of BMSCs and the mismatch between bone regeneration and growth factors release constrain their effectiveness in treating critical bone defects.Drawing inspiration from the regenerative properties of BM,we developed self-assembled hybrid microspheres to replicate its function and address these challenges through a tissue engineering approach.This BM-mimicking niche enriched BMSCs via fast-degrading gelatin methacryloyl(GelMA)microspheres,which were loaded with exogenous BMSCs and conjugated with stem cell homing peptides(SKP)to recruit endogenous BMSCs.SKP further enhanced the stemness of BMSCs,thereby promoting angiogenesis and resolving inflammation.Slow-degrading chitosan methacryloyl(ChitoMA)microspheres facilitated sustained release of angiogenic(KLT)and osteogenic(OGP)peptides,supporting blood vessel maturation and osteogenesis.The early release of BMSCs and SKP,followed by the subsequent release of OGP and KLT,aligned with the dynamic process of bone regeneration.In a rat critical femoral condyle defect model,the BM-mimicking niche formed an in-situ ossification center,significantly enhancing bone regeneration.This study introduces a novel BM-mimicking niche characterized by a BMSC-enriched environment and the sequential release of therapeutic factors,offering a promising strategy for treating critical bone defects.
基金This study was supported by the National Natural Science Foundation of China （NSFC） （No. 81671829）.
文摘Molybdenum disulfide （MoS2）, a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging （MRI）-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe3O4@MoS2 nanocubes （IOMS NCs） via the integration of MoS2 （MS） film onto iron oxide （IO） nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose （2-DG）, a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG- modified PEGylated NCs （IOMS-PEG-2DG NCs） acted as drug-carriers for doxorubicin （DOX）, which could be easily loaded within the NCs. The obtained IOMS-PEG（DOX）-2DG NCs exhibited a 3？2 relaxivity coefficient of 48.86 （mM）^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG（DOX）-2DG NCs, the tumor site was clearly detected by enhanced T2-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 rain at a low power density of 0.5 W·cm^-2 a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.
文摘Nerve guidance conduit （NGC） is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube （hCST） to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide （RGI, RGIDKRHWNSQ） derived from brain-derived neurotrophic factor （BDNF） to the C-terminus of the self-assembling peptide RADA16-I （Ac-（RADA）4-CONH2）. Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.
基金supported by Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(20191080871)the National Natural Science Foundation of China(82272464,82002314).
文摘Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.
基金the National Natural Science Foundation of China(31771056 and 81200931)the Tsinghua University Initiative Scientific Research Program(20161080091)+1 种基金the 111 Project(B17026)a special fund from Key laboratory of Neurodegenerative diseases,Ministry of Education(PXM2019_026283_000002).
文摘Angiogenesis plays an important role in brain injury repair,which contributes to the reconstruction of regenerative neurovascular niche for promoting axonal regeneration in the lesion area.As a major component of developing brain extracellular matrix,hyaluronic acid(HA)has attracted more attention as a supporting matrix for brain repair.In the present study,HA-KLT hydrogel was developed via modifying HA with a VEGF mimetic peptide of KLT(KLTWQELYQLKYKGI).The characterization of the hydrogel shows that it could provide a porous,three-dimensional scaffold structure,which has a large specific surface area available for cell adhesion and interaction.Compared with the unmodified HA hydrogel,the HA-KLT hydrogel could effectively promote the attachment,spreading and proliferation of endothelial cells in vitro.Furthermore,the pro-angiogenic ability of hydrogels in vivo was evaluated by implanting them into the lesion cavities in the injured rat brain.Our results showed that the hydrogels could form a permissive interface with the host tissues at 4 weeks after implantation.Moreover,they could efficiently inhibit the formation of glial scars at the injured sites.The HA-KLT hydrogel could significantly increase the expression of endoglin/CD105 and promote the formation of blood vessels,suggesting that HA-KLT hydrogel promoted angiogenesis in vivo.Collectively,the HA-KLT hydrogel has the potential to repair brain defects by promoting angiogenesis and inhibiting the formation of glial-derived scar tissue.
文摘Recently, increasing attention has been paid to magneto-conjugated polymer core-shell nanoparticles （NPs） as theranostic platforms. However, the utilization of surfactants and extra oxidizing agents with potential toxicity in synthesis, the lack of general methods for the controlled synthesis of various kinds of magnetic NP （MNP）@conjugated polymer NPs, and the difficulty of obtaining balanced magneto-optical properties have greatly limited the applications of magneto-conjugated polymers in theranostics. We developed an in situ surface polymerization method free of extra surfactants and oxidizing agents to synthesize MNP@polypyrrole （PPy） NPs with balanced, prominent magneto-optical properties. MNP@PPy NPs with an adjustable size, different shapes, and a controlled shell thickness were obtained using this method. The method was extended to synthesize other MNP-conjugated polymer core-shell NPs, such as MNP@polyaniline and MNP@poly（3,4-ethylenedioxythiophene）：poly（4- styrenesulfonate） （PEDOT：PSS）. We discuss the formation mechanism of the proposed method according to our experimental results. Finally, using the optical and magnetic properties of the obtained MNP@PEDOT：PSS NPs, in vivo multimodal imaging-guided hyperthermia was induced in mice, achieving an excellent tumor-ablation therapeutic effect. Our work is beneficial for extending the application of MNP-conjugated polymer core-shell NPs in the biomedical field.
文摘Adult central nervous system （CNS） tissue has a limited capacity to recover after trauma or disease. Recent medical cell therapy using polymeric biomaterial- loaded stem cells with the capability of differentiation to specific neural population has directed focuses toward the recovery of CNS. Fibers that can provide topographical, biochemical and electrical cues would be attractive for directing the differentiation of stem cells into electro-responsive cells such as neuronal cells. Here we report on the fabrication of an electrospun polypyrrole/polylactide composite nanofiber film that direct or determine the fate of mesenchymal stem cells （MSCs）, via combination of aligned surface topography, and electrical stimulation （ES）. The surface morphology, mechanical properties and electric properties of the film were characterized. Comparing with that on random surface film, expression of neurofilament-lowest and nestin of human umbilical cord mesenchymal stem cells （huMSCs） cultured on film with aligned surface topography and ES were obviously enhanced. These results suggest that aligned topography combining with ES facilitates the neurogenic differentiation of huMSCs and the aligned conductive film can act as a potential nerve scaffold.
基金support from the National Key R&D Program of China(Nos.2020YFC1107600 and 2018YFB0704304)the National Natural Science Foundation of China(Nos.31771056 and 31771052)Shandong Province Key R&D Program of China(No.2019JZZY011106).
文摘The coordination between neurogenesis and angiogenesis plays an important role in nerve tissue development and regeneration.Recently,using bioactive materials to drive neurogenic and angiogenic responses has gained increasing attention.Understanding the neurovascular link between regulatory cues offers valuable insight into the mechanisms underlying nerve regeneration and the design of new bioactive materials.In this study,we utilized a dual-functionalized peptide nanofiber hydrogel presenting the brain-derived neurotrophic factor and vascular endothelial growth factor mimetic peptides RGIDKRHWNSQ(RGI)and KLTWQELYQLKYKGI(KLT)to construct an artificial neurovascular microenvironment.The dual-functionalized peptide nanofiber hydrogel enhanced the neurite outgrowth of pheochromocytoma(PC12)cells and tube-like structures formation of human umbilical vein endothelial cells(HUVECs)in vitro,and promoted rapid lesion infiltration of neural and vascular cells in a rat brain injury model.Using indirect co-culture models,we found that the dual-functionalized peptide hydrogel effectively mediated neurovascular crosstalk by regulating secretion of paracrine factors from PC12 cells and HUVECs.When the two cells types were directly co-cultured on the dua卜functionalized peptide hydrogel,the efficiency of cell-cell communication was enhanced,which further accelerated the differentiation and maturation of PC12 cells with an increased number of pseudopodia and spread morphology,and HUVECs tube-like structure formation.In summary,the dual-functionalized peptide nanofiber hydrogel successfully formed an artificial neurovascular niche to directly regulate the behaviors of neural and vascular cells and promote their neurovascular crosstalk through paracrine signaling and direct cell-cell contact.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.52072210 and 52111530230)Key R&D Projects of Social Development of Hainan Provincial Department of Science and Technology(Grant No.ZDYF2020137)Tsinghua University Beijing Union Medical CollegeeHospital Cooperation Project(Grant No.20191080871).
文摘The disruption and reconstruction of the TREM2^(+) tissue resident macrophage(TRM)barrier on the surface of synovial lining play a key role in the activation and"remission"of rheumatoid arthritis(RA),which engender the prediction of this immunologic barrier as a potential driver for the achievement of"cure"in RA.However,strategies to promote the reconstruction of this barrier have not been reported,and the effect of patching this barrier remains unidentified.On the other hand,appropriate piezoelectric stimulation can reprogram macrophages,which has never been exerted on this barrier TRM yet.Herein,we design piezoelectric tetragonal BaTiO_(3)(BTO)ultrasound-driven nanorobots(USNRs)by the solvothermal synthesis method,which demonstrates satisfactory electro-mechanical conversion effects,paving the way to generate controllable electrical stimulation under ultrasound to reprogram the barrier TRM by minimally invasive injection into joint cavity.It is demonstrated that the immunologic barrier could be patched by this USNR effectively,thereby eliminating the hyperplasia of vessels and nerves(HVN)and synovitis.Additionally,TREM2 deficiency serum-transfected arthritis(STA)mice models are applied and proved the indispensable role of TREM2 in RA curing mediated by USNR.In all,our work is an interesting and important exploration to expand the classical tetragonal BTO nanoparticles in the treatment of autoimmune diseases,providing a new idea and direction for the biomedical application of piezoelectric ceramics.
文摘The induction time of cefodizime sodium was measured in ethanol-water at different solvent composi- tions by the laser technology measurement. The results indicate that the solvent composition played an important role in the supersaturation and the nucleation process of cefodizime sodium solution. According to the modified classical nucleation theory, the nucleation and growth mechanism were identified. The correlation results show that heterogeneous nucleation dominated the nucleation process at lower supersaturation, where homogeneous nucleation is the most important mechanism at higher supersaturation. Based on the correlated results, the 2D mediated growth mechanism had the highest correlation coefficients （R2）, so this mechanism was selected as the proper growth mechanism for cefodizime sodium.
基金funded by the National Key R&D Program of China(No.2020YFC1107601)The Foshan-Tsinghua Innovation Special Fund(No.2020THFS05)the Key R&D Program in Shandong Province(2019JZZY011106).
文摘A new nerve guidance conduits(NGCs)named MC@Col containing Type I collagen(Col)and mineralized collagen(MC)was developed,enhancing mechanical and degradation behavior.The physicochemical properties,the mechanical properties and in vitro degradation behavior were all evaluated.The adhesion and proliferation of Schwann cells(SCs)were observed.In the in vivo experiment,MC@Col NGC and other conduits including Col,chitosan(CST)and polycaprolactone(PCL)conduit were implanted to repair a 10-mm-long Sprague-Dawley rat’s sciatic nerve defect.Histological analyses,morphological analyses,electrophysiological analyses and further gait analyses were all evaluated after implantation in 12 weeks.The strength and degradation performance of the MC@Col NGC were improved by the addition of MC in comparison with pure Col NGC.In vitro cytocompatibility evaluation revealed that the SCs had good viability,attachment and proliferation in the MC@Col.In in vivo results,the regenerative outcomes of MC@Col NGC were close to those by an autologous nerve graft in some respects,but superior to those by Col,CST and PCL conduits.The MC@Col NGC exhibited good mechanical performance as well as biocompatibility to bridge nerve gap and guide nerve regeneration,thus showing great promising potential as a new type of conduit in clinical applications.
