Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we use...Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.展开更多
In order to understand the status of business model and scale business of maize in Shiyan City,Hubei Province,the situation of maize production in 314 households of 6 counties and cities of Shiyan City was investigate...In order to understand the status of business model and scale business of maize in Shiyan City,Hubei Province,the situation of maize production in 314 households of 6 counties and cities of Shiyan City was investigated in terms of rural basic situation,business models,economic benefits and scale business. Targeting at the actual problems in business models and scale business,corresponding countermeasures of actively promoting the construction of industrialized business mechanism,improving the construction of agricultural infrastructure,strengthening land transfer management and promoting scientific and technological progress and innovation were put forward to provide reference for the future scale development of maize in Shiyan City.展开更多
In order to study the current situation of land transfer in the process of agricultural industrialization in the Qinling-Daba Mountains(Shiyan),27 villages of 14 townships(towns) of six counties(cities) were visited a...In order to study the current situation of land transfer in the process of agricultural industrialization in the Qinling-Daba Mountains(Shiyan),27 villages of 14 townships(towns) of six counties(cities) were visited and investigated through questionnaires,and the current situation and characteristics of land transfer among large professional households( large grain producers),family farms,agricultural enterprises and cooperatives in the process of agricultural industrialization were analyzed and summarized. The main issues affecting land transfer were summarized,such as big difference of inflow and outflow will,single way of land transfer,high cost of planting,weak agricultural infrastructure,a lack of production and operation technology,insufficient funds and short land transfer period,and imperfect social security system.Meanwhile,some countermeasures were proposed,such as improving land transfer system,precise subsidy policy and social security mechanism of Shiyan City,guiding long-term and normalized land transfer,strengthening training of professional skills and improving the quality of human resources,actively promoting the " three-township project",and attracting the investment in land transfer projects.展开更多
Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel wi...Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.展开更多
Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present uni...Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones,and thus are highly desired.The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature.In this review,we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine.We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts.As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites,the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites.The inorganic particles that are covered in this review are categorised into two broad types(1)solid(e.g.,calcium phosphate,hydroxyapatite,etc.)and(2)porous particles(e.g.,mesoporous silica,porous silicon etc.),which are elaborated in detail with recent examples.The review also covers other new types of inorganic material(e.g.,2D inorganic materials,clays,etc.)based polymer composites for tissue engineering applications.Lastly,we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.展开更多
Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based...Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.展开更多
The problem of task assignment for multiple cooperating unmanned aerial vehicle(UAV) teams is considered. Multiple UAVs forming several small teams are needed to perform attack tasks on a set of predetermined ground t...The problem of task assignment for multiple cooperating unmanned aerial vehicle(UAV) teams is considered. Multiple UAVs forming several small teams are needed to perform attack tasks on a set of predetermined ground targets. A hierarchical task assignment method is presented to address the problem. It breaks the original problem down to three levels of sub-problems: target clustering, cluster allocation and target assignment. The first two sub-problems are centrally solved by using clustering algorithms and integer linear programming, respectively, and the third sub-problem is solved in a distributed and parallel manner, using a mixed integer linear programming model and an improved ant colony algorithm. The proposed hierarchical method can reduce the computational complexity of the task assignment problem considerably, especially when the number of tasks or the number of UAVs is large. Experimental results show that this method is feasible and more efficient than non-hierarchical methods.展开更多
Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treat...Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.展开更多
Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of ...Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of mesoporous silica rods with large cone-shaped pores(MSR-CP)to load and deliver large protein drugs.It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage.Furthermore,bone morphogenetic proteins 2(BMP-2)loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.In vivo tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance.This study provides a potential strategy for the design of drug delivery systems for bone regeneration.展开更多
Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironmen...Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.展开更多
Autophagy has been extensively studied and occurs in many biological settings.However,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has be...Autophagy has been extensively studied and occurs in many biological settings.However,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has been previously thought.Furthermore,the effect of the level of autophagy on cell or skin flap survival still requires elucidation.We created a lethal ischemia model in human umbilical vascular endothelial cells(HUVECs),performed quantitative proteomics and bioinformatics analyses,and verified the autophagic status and effect both in vitro and in vivo.The significantly upregulated proteins encoded by autophagy-related genes(ATGs)included ATG2A,ATG3,ATG4B,ATG5,ATG7,ATG9A,ATG12,ATG16,and ATG101.The significantly enhanced lysosomal proteins were cathepsin B,cathepsin D,lysosome-associated membrane protein 1(LAMP1),and LAMP2.However,the differentially expressed proteins excluded Beclin-1,microtubule-associated protein light chain 3(LC3)-I,and LC3-II.Western blot analyses verified that the protein expression levels of Beclin-1,LC3-I,and LC3-II were neither upregulated nor downregulated in ischemia-challenged HUVECs.The autophagic status was not enhanced by rapamycin in ischemic HUVECs but appeared to be inhibited by chloroquine.Our in vivo study on rats showed that a downregulation in autophagic status jeopardized skin flap survival.In conclusion,Ischemia neither enhanced nor inhibited Beclin-1/LC3-II-dependent canonical macroautophagy both in vitro and in vivo,in contradiction to previous studies.An appropriate autophagic homeostasis can minimize cell or skin flap damage.展开更多
Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult ne...Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.展开更多
Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in allevia...Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.展开更多
A magnesium alloy containing essential,non-toxic,biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process(TRC).Microstructure,mechanical properties,in vivo corrosion and bio...A magnesium alloy containing essential,non-toxic,biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process(TRC).Microstructure,mechanical properties,in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth(RE)element containing WE43 alloy.TRC Mg-0.5 wt% Zn-0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150μm.Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%.The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51±0.07 mm/y similar to that of the WE43 alloy(0.47±0.09 mm/y)in the rat model after 1 week of implantation.By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant.The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation.The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.展开更多
The authors regret that the author(A.H.)was removed as an agreement could not be reached between the two affiliations of the author.The authors would like to apologise for any inconvenience caused.
基金supported by the National Natural Science Foundation of China,Nos.81971870 and 82172173 (both to ML)。
文摘Human dental pulp stem cells(hDPSCs) promote recovery after ischemic stro ke;however,the therapeutic efficacy is limited by the poor survival of transplanted cells.For in vitro expe riments in the present study,we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion.We found that miRNA-34a-5p(miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs.Inhibition of miR-34a facilitated the prolife ration and antioxidant capacity and reduced the apoptosis of hDPSCs.Moreove r,dual-luciferase reporter gene assay showed WNT1and SIRT1 as the targets of miR-34a.In miR-34a knockdown cell lines,WNT1 suppression reduced cell prolife ration,and SIRT1 suppression decreased the antioxidant capacity.Togethe r,these results indicated that miR-34a regulates cell prolife ration and antioxidant stress via targeting WNT1 and SIRT1,respectively.For in vivo expe riments,we injected genetically modified hDPSCs(anti34a-hDPSCs) into the brains of mice.We found that anti34a-hDPSCs significantly inhibited apoptosis,reduced cerebral edema and cerebral infarct volume,and improved motor function in mice.This study provides new insights into the molecular mechanism of the cell prolife ration and antioxidant capacity of hDPSCs,and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.
基金Supported by Hubei Provincial Collaborative Innovation Center for Industrialization of Major Grain Crops(2014.5.13)Technical Innovation Fund of Department of Science and Technology of Hubei Province(2017ABA070)
文摘In order to understand the status of business model and scale business of maize in Shiyan City,Hubei Province,the situation of maize production in 314 households of 6 counties and cities of Shiyan City was investigated in terms of rural basic situation,business models,economic benefits and scale business. Targeting at the actual problems in business models and scale business,corresponding countermeasures of actively promoting the construction of industrialized business mechanism,improving the construction of agricultural infrastructure,strengthening land transfer management and promoting scientific and technological progress and innovation were put forward to provide reference for the future scale development of maize in Shiyan City.
基金Supported by the Project of Hubei Provincial Department of EducationHubei Provincial Department of Finance"Hubei Collaborative Innovation Center for Industrialization of Major Food Crops(2014.5)"
文摘In order to study the current situation of land transfer in the process of agricultural industrialization in the Qinling-Daba Mountains(Shiyan),27 villages of 14 townships(towns) of six counties(cities) were visited and investigated through questionnaires,and the current situation and characteristics of land transfer among large professional households( large grain producers),family farms,agricultural enterprises and cooperatives in the process of agricultural industrialization were analyzed and summarized. The main issues affecting land transfer were summarized,such as big difference of inflow and outflow will,single way of land transfer,high cost of planting,weak agricultural infrastructure,a lack of production and operation technology,insufficient funds and short land transfer period,and imperfect social security system.Meanwhile,some countermeasures were proposed,such as improving land transfer system,precise subsidy policy and social security mechanism of Shiyan City,guiding long-term and normalized land transfer,strengthening training of professional skills and improving the quality of human resources,actively promoting the " three-township project",and attracting the investment in land transfer projects.
基金This study was partly funded by grants from the National Natural Science Funding of China(82172424,82271629)Outstanding Youth Fund of Zhejiang Province(LR22H060002)+2 种基金Zhejiang Medical and Health Science and Technology Plan Project(2022RC210,2021KY212)Wenzhou Basic Science Research Plan Project(Y20210045)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Spinal cord injury(SCI)is a serious clinical disease.Due to the deformability and fragility of the spinal cord,overly rigid hydrogels cannot be used to treat SCI.Hence,we used TPA and Laponite to develop a hydrogel with shear-thinning ability.This hydrogel exhibits good deformation,allowing it to match the physical properties of the spinal cord;additionally,this hydrogel scavenges ROS well,allowing it to inhibit the lipid peroxidation caused by ferroptosis.According to the in vivo studies,the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism.In addition,dental pulp stem cells(DPSCs)were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses.It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.
基金the support from the National Health and Medical Research Council of Australia(NHMRC)for Early Career Fellowship(GNT1143296)the University of New South Wales for support and Scientia Grant.Q.Y.acknowledges the support Key R&D Program of China(2022YFC2504200,2022BCA029 of Hubei)the Research and Development Office,Ministry of Education-Saudi Arabia for the International Collaboration Initiative grant(#5011).
文摘Biomaterials have ushered the field of tissue engineering and regeneration into a new era with the development of advanced composites.Among these,the composites of inorganic materials with organic polymers present unique structural and biochemical properties equivalent to naturally occurring hybrid systems such as bones,and thus are highly desired.The last decade has witnessed a steady increase in research on such systems with the focus being on mimicking the peculiar properties of inorganic/organic combination composites in nature.In this review,we discuss the recent progress on the use of inorganic particle/polymer composites for tissue engineering and regenerative medicine.We have elaborated the advantages of inorganic particle/polymer composites over their organic particle-based composite counterparts.As the inorganic particles play a crucial role in defining the features and regenerative capacity of such composites,the review puts a special emphasis on the various types of inorganic particles used in inorganic particle/polymer composites.The inorganic particles that are covered in this review are categorised into two broad types(1)solid(e.g.,calcium phosphate,hydroxyapatite,etc.)and(2)porous particles(e.g.,mesoporous silica,porous silicon etc.),which are elaborated in detail with recent examples.The review also covers other new types of inorganic material(e.g.,2D inorganic materials,clays,etc.)based polymer composites for tissue engineering applications.Lastly,we provide our expert analysis and opinion of the field focusing on the limitations of the currently used inorganic/organic combination composites and the immense potential of new generation of composites that are in development.
基金This work was supported by the National Natural Science Foundation of China(81871503 from Qingsong Ye)National Key R&D Program of China(2022YFC2504200 from Qingsong Ye)Key research and development project of Hubei Province and Chutian Researcher Project(X22020024 from Yan He).
文摘Mesenchymal stem cells(MSCs)are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility.They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders,including neural differentiation,immunosuppression,neurotrophy,and safety.However,the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases.To improve some of their abilities,many studies have employed genetic engineering to transfer key genes into MSCs.Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties.However,to date,different modes of gene transfer have specific drawbacks and advantages.In addition,MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation,enhancing neurotrophic and neuroprotective functions,and increasing survival and homing abilities.The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function.In this review,we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes.Further,we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.
基金supported by the National Natural Science Foundation of China(7147205871401048)the Fundamental Research Funds for the Central Universities(2012HGZY0009)
文摘The problem of task assignment for multiple cooperating unmanned aerial vehicle(UAV) teams is considered. Multiple UAVs forming several small teams are needed to perform attack tasks on a set of predetermined ground targets. A hierarchical task assignment method is presented to address the problem. It breaks the original problem down to three levels of sub-problems: target clustering, cluster allocation and target assignment. The first two sub-problems are centrally solved by using clustering algorithms and integer linear programming, respectively, and the third sub-problem is solved in a distributed and parallel manner, using a mixed integer linear programming model and an improved ant colony algorithm. The proposed hierarchical method can reduce the computational complexity of the task assignment problem considerably, especially when the number of tasks or the number of UAVs is large. Experimental results show that this method is feasible and more efficient than non-hierarchical methods.
基金supported by the National Natural Science Funding of China(81701032,81871503)the Wenzhou Science and Technology Association Project,the Wenzhou Major Scientific and Technological Innovation Key Medical and Health Project(ZY2019010)+4 种基金the Wenzhou Medical University grant(QTJ16026)Wenzhou Science and Technology Association Project,Wenzhou Basic Research Project(Y20180131)Zhejiang Province Program of the Medical and Health Science and Technology(2018KY537)Zhejiang Natural Science Foundation(LGF18C100002)Zhejiang Xinmiao Talents Program(2018R413186).
文摘Due to the limitations in autogenous nerve grafting or Schwann cell transplantation,large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit.Cell based therapies provide a novel treatment for peripheral nerve injuries.In this study,we first experimented an optimal scaffold material synthesis protocol,from where we selected the 10%GFD formula(10%GelMA hydrogel,recombinant human basic fibroblast growth factor and dental pulp stem cells(DPSCs))to fill a cellulose/soy protein isolate composite membrane(CSM)tube to construct a third generation of nerve regeneration conduit,CSM-GFD.Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model.After 12 week post implant surgery,at histologic level,we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers.At physical level,CSM-GFD achieved functional recovery assessed by a sciatic functional index study.In both levels,CSM-GFD performed like what gold standard,the nerve autograft,could do.Further,we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD.In conclusion,we claimed that this third-generation nerve regeneration conduit,CSM-GFD,could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.
基金The authors acknowledge the support from UQ Early Career Researcher Grant(1717673)the National Natural Science Foundation of China(Nos.81871503 and 81701032)+2 种基金C.X.acknowledges the support of National Health&Medical Research Council of Australia(NHMRC)Early Career FellowshipY.H.,L.X.and C.L.extended their appreciations to the support of Advanced QueenslandThe authors acknowledge the support from the Australian Microscopy and Microanalysis Research Facility at the Centre for Microscopy and Microanalysis,the University of Queensland.
文摘Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules,such as bone morphogenetic proteins,are desired for bone regeneration.Herein,we report the development of mesoporous silica rods with large cone-shaped pores(MSR-CP)to load and deliver large protein drugs.It is noted that those cone-shaped pores on the surface modulated the immune response and reduced the pro-inflammatory reaction of stimulated macrophage.Furthermore,bone morphogenetic proteins 2(BMP-2)loaded MSR-CP facilitated osteogenic differentiation and promoted osteogenesis of bone marrow stromal cells.In vivo tests confirmed BMP-2 loaded MSR-CP improved the bone regeneration performance.This study provides a potential strategy for the design of drug delivery systems for bone regeneration.
基金This work was supported by the National Natural Science Foundation of China(Grant No.:NSFC 81871493,81871503)the Medical Science Advancement Program(Clinical Medicine)of Wuhan University(Grant No.:TFLC2018002,2018003)。
文摘Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.
基金This work was supported by the National Natural Science Foundation of China(No.81400493)Scientific and Technological Research Program of Chongqing Municipal Education Commission(No.KJQN20200429)Joint Medical Research Project by Chongqing Health Commission and Natural Science Foundation of Chongqing(No.2020GDRC008).
文摘Autophagy has been extensively studied and occurs in many biological settings.However,a question remains as to whether ischemia enhances Beclin-1/LC3-II-dependent macroautophagy in vascular endothelial cells,as has been previously thought.Furthermore,the effect of the level of autophagy on cell or skin flap survival still requires elucidation.We created a lethal ischemia model in human umbilical vascular endothelial cells(HUVECs),performed quantitative proteomics and bioinformatics analyses,and verified the autophagic status and effect both in vitro and in vivo.The significantly upregulated proteins encoded by autophagy-related genes(ATGs)included ATG2A,ATG3,ATG4B,ATG5,ATG7,ATG9A,ATG12,ATG16,and ATG101.The significantly enhanced lysosomal proteins were cathepsin B,cathepsin D,lysosome-associated membrane protein 1(LAMP1),and LAMP2.However,the differentially expressed proteins excluded Beclin-1,microtubule-associated protein light chain 3(LC3)-I,and LC3-II.Western blot analyses verified that the protein expression levels of Beclin-1,LC3-I,and LC3-II were neither upregulated nor downregulated in ischemia-challenged HUVECs.The autophagic status was not enhanced by rapamycin in ischemic HUVECs but appeared to be inhibited by chloroquine.Our in vivo study on rats showed that a downregulation in autophagic status jeopardized skin flap survival.In conclusion,Ischemia neither enhanced nor inhibited Beclin-1/LC3-II-dependent canonical macroautophagy both in vitro and in vivo,in contradiction to previous studies.An appropriate autophagic homeostasis can minimize cell or skin flap damage.
基金This study was partly funded by a grant the National Natural Science Foundation of China(81802235,81871503),Zhejiang Medical and Health Science and Technology Plan Project(2021KY212),and Wenzhou Basic Science Research Plan Project(Y2020050),Advanced Postdoctoral Programs of Zhejiang(zj2019030),China Postdoctoral Science Foundation(2019M662015),CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028).
文摘Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.
基金This work was supported by grants from Advanced Postdoctoral Programs of Zhejiang(zj2019030)China Postdoctoral Science Foundation(2019M662015)+1 种基金Research Unit of Research and Clinical Translation of Cell Growth Factors and Diseases,Chinese Academy of Medical Science(No.2019RU010 to X.L.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-028),China.
文摘Heart disease is still the leading killer all around the world,and its incidence is expected to increase over the next decade.Previous reports have already shown the role of fibroblast growth factor10(FGF10)in alleviating heart diseases.However,FGF10 has not been used to treat heart diseases because the free protein has short half-life and low bioactivity.Here,an injectable coacervate was designed to protect growth factor from degradation during delivery and the effects of the FGF10 coacervate were studied using a mice acute myocardial infarction(MI)model.As shown in our echocardiographic results,a single injection of FGF10 coacervate effectively inhibited preserved cardiac contractibility and ventricular dilation when compared with free FGF10 and the saline treatment 6 weeks after MI.It is revealed in histological results that the MI induced myocardial inflammation and fibrosis was reduced after FGF10 coacervate treatment.Furthermore,FGF10 coacervate treatment could improve arterioles and capillaries stabilization through increasing the proliferation of endothelial and mural cells.However,with the same dosage,no statistically significant difference was shown between free FGF10,heparin+FGF10 and saline treatment,especially in long term.On another hand,FGF10 coacervate also increased the expression of cardiac-associated the mRNA(cTnT,Cx43 and α-SMA),angiogenic factors(Ang-1 and VEGFA)and decreased the level of inflammatory factor(tumor necrosis factor-α).The downstream signaling of the FGF10 was also investigated,with the western blot results showing that FGF10 coacervate activated the p-FGFR,PI3K/Akt and ERK1/2 pathways to a more proper level than free FGF10 or heparin+FGF10.In general,it is revealed in this research that one-time injection of FGF10 coacervate sufficiently attenuated MI induced injury when compared with an equal dose of free FGF10 or heparin+FGF10 injection.
基金the support of the Australian Research Council through the ARC Research Hub for Advanced Manufacturing of Medical Devices(IH150100024).
文摘A magnesium alloy containing essential,non-toxic,biodegradable elements such as Ca and Zn has been fabricated using a novel twin-roll casting process(TRC).Microstructure,mechanical properties,in vivo corrosion and biocompatibility have been assessed and compared to the properties of the rare earth(RE)element containing WE43 alloy.TRC Mg-0.5 wt% Zn-0.5 wt% Ca exhibited fine grains with an average grain size ranging from 70 to 150μm.Mechanical properties of a TRC Mg-0.5Zn-0.5Ca alloy showed an ultimate tensile strength of 220 MPa and ductility of 9.3%.The TRC Mg-0.5Zn-0.5Ca alloy showed a degradation rate of 0.51±0.07 mm/y similar to that of the WE43 alloy(0.47±0.09 mm/y)in the rat model after 1 week of implantation.By week 4 the biodegradation rates of both alloys studied were lowered and stabilized with fewer gas pockets around the implant.The histological analysis shows that both WE43 and TRC Mg-0.5Zn-0.5Ca alloy triggered comparable tissue healing responses at respective times of implantation.The presence of more organized scarring tissue around the TRC Mg-0.5Zn-0.5Ca alloys suggests that the biodegradation of the RE-free alloy may be more conducive to the tissue proliferation and remodelling process.
文摘The authors regret that the author(A.H.)was removed as an agreement could not be reached between the two affiliations of the author.The authors would like to apologise for any inconvenience caused.
