Exceeding probability analysis for rail of high-speed railway under seismic excitations

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.

Organic mulching promotes soil organic carbon accumulation to deep soil layer in an urban plantation forest

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.

Dynamic corner frequency in source spectral model for stochastic synthesis of ground motion

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.

In vivo evaluation of additively manufacturedmulti-layered scaffold for the repair of large osteochondral defects

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.

Response of nitrogen fractions in the rhizosphere and bulk soil to organic mulching in an urban forest plantation

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.

Snow disaster characteristics in Palongzangbu River Basinand mitigation countermeasures for road engineering

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.

Stochastic simulation of ground motions based on NGA-West2 strong motion records

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.

耐盐碱解磷菌Bacillus sp.DYS211对土壤磷溶解和植物生长的促进作用

土壤全磷含量高而速效磷含量不足严重制约盐碱地区磷的高效利用。虽然耐盐碱解磷菌可以溶解不溶性磷,但很少有研究关注其在植物生长中的应用。我们从盐碱地区鸟粪中分离到一株解磷菌,鉴定命名为Bacillus sp.DYS211,并对其生长特性和耐盐碱能力进行了测定。为研究解磷菌对植物种子萌发和生长的影响,在盐地碱蓬中进行解磷菌添加的盆栽试验。该解磷菌菌株在培养前12 h生长迅速,48 h时溶磷量最大,达到258.22 mg L^(−1)。耐盐碱性和解磷能力试验表明,DYS211倾向于溶解无机磷,为嗜盐菌,在1%–8%盐度条件下具有良好的解磷效果(有效磷含量>150 mg L^(−1))。在葡萄糖和蔗糖(C源)以及硫酸铵、硝酸铵和酵母浸膏粉(N源)中均表现出较好的解磷能力。在促生长试验中,该解磷菌对种子萌发有促进作用,特别是在高盐胁迫下,促进率为8.33%。在盐碱条件下,解磷菌均能显著提高盐地碱蓬的株高和生物量(最高可达3倍),且高盐胁迫下茎粗增加。该菌株表现出在盐碱地区植被恢复中的潜力。

Ultrasound-driven BaTiO_(3) nanorobots patching immunologic barrier to cure chronic rheumatoid arthritis

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.

Continuously released Zn^(2+)in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties

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.

Corrigendum to“Development of methods for detecting the fate of mesenchymal stem cells regulated by bone bioactive materials”[Bioact.Mater.6(3)(2021)613-626]

The authors regret that the last name and first name of all authors are reversed in the original article.The correct writing is as follows:Le Jiang,a,b#;Zhongqun Liu,a,b#;Zhaoyan Wang,d,e,f;Yijun Su,a,b;Yingjin Wang,a,b;Yaojie Wei,a,b;Yanan Jiang,c;Zhanrong Jia,c;Chunyang Ma,a,b;Fangli Gang,a,b;Nan Xu,a,b;Lingyun Zhao,a,b;Xiumei Wang,a,b;Qiong Wu,d,e,f;Xiong Lu,c,*and Xiaodan Sun,a,b,*a.State Key Laboratory of New Ceramics and Fine Processing,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;b.Key Laboratory of Advanced Materials of Ministry of Education of China,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,People’s Republic of China;c.Key Lab of Advanced Technologies of Materials of Ministry of Education,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu 610031,People’s Republic of China d.MOE Key Laboratory of Bioinformatics,Tsinghua University,Beijing,100084,People’s Republic of China e.Center for Synthetic and Systems Biology,Tsinghua University,Beijing,100084,People’s Republic of China f.School of Life Sciences,Tsinghua University,Beijing,100084,People’s Republic of China.

A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

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.

Enhanced angiogenesis by the hyaluronic acid hydrogels immobilized with a VEGF mimetic peptide in a traumatic brain injury model in rats

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.

Neurogenic differentiation of human umbilical cord mesenchymal stem cells on aligned electrospun polypyrrole/ polylactide composite nanofibers with electrical stimulation

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.

Doxorubicin-Ioaded Fe3O4@MoS2-PEG-2DG nanocubes as a theranostic platform for magnetic resonance imaging- guided chemo-photothermal therapy of breast cancer

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.

Crosstalk between PC 12 cells and endothelial cells in an artificial neurovascular niche constructed by a dual-functionalized selfassembling peptide nanofiber hydrogel

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.

Nucleation and growth mechanism of cefodizime sodium at different solvent compositions

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.

General synthesis of high-performing magneto-conjugated polymer core-shell nanoparticles for multifunctional theranostics

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.

Osteochondral scaffolds for early treatment of cartilage defects in osteoarthritic joints:from bench to clinic

Osteoarthritis is a degenerative joint disease,typified by the loss in the quality of cartilage and bone at the interface of a synovial joint,resulting in pain,stiffness and reduced mobility.The current surgical treatment for advanced stages of the disease is joint replacement,where the non-surgical therapeutic options or less invasive surgical treatments are no longer effective.These are major surgical procedures which have a substantial impact on patients’quality of life and lifetime risk of requiring revision surgery.Treatments using regenerative methods such as tissue engineering methods have been established and are promising for the early treatment of cartilage degeneration in osteoarthritis joints.In this approach,3-dimensional scaffolds(with or without cells)are employed to provide support for tissue growth.However,none of the currently available tissue engineering and regenerative medicine products promotes satisfactory durable regeneration of large cartilage defects.Herein,we discuss the current regenerative treatment options for cartilage and osteochondral(cartilage and underlying subchondral bone)defects in the articulating joints.We further identify the main hurdles in osteochondral scaffold development for achieving satisfactory and durable regeneration of osteochondral tissues.The evolution of the osteochondral scaffolds–from monophasic to multiphasic constructs–is overviewed and the osteochondral scaffolds that have progressed to clinical trials are examined with respect to their clinical performances and their potential impact on the clinical practices.Development of an osteochondral scaffold which bridges the gap between small defect treatment and joint replacement is still a grand challenge.Such scaffold could be used for early treatment of cartilage and osteochondral defects at early stage of osteoarthritis and could either negate or delay the need for joint replacements.

White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in canine T12 spinal cord injury

A hierarchically aligned fibrin hydrogel(AFG)that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo.However,its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified.Here,the effects of AFG on directing neuroregeneration in canine hemisected T12 spinal cord injuries were explored.Histologically obvious white matter regeneration consisting of a large area of consecutive,compact and aligned nerve fibers is induced by AFG,leading to a significant motor functional restoration.The canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks.Moreover,high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group.Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion,pointing out its promising prospect in clinic practice.