The aim of this study is to unveil the role of integrin in influencing the differentiation of PC12 cell grown on PLLA aligned nanofibers by integrative study of cDNA microarray,proteomics technology and microRNA seque...The aim of this study is to unveil the role of integrin in influencing the differentiation of PC12 cell grown on PLLA aligned nanofibers by integrative study of cDNA microarray,proteomics technology and microRNA sequencing technology.First,PLLA-aligned nanofibers were prepared by electrospinning,and the chemical composition and surface morphology of the nanofibers were examined.Then,morphology and neurite length of PC12 cells and GRGDS-treated PC12 cells on PLLA-aligned nanofibers(AF and GA group)were measured by high-content analysis system.Subsequently,protein expression profile was analyzed by iTRAQ proteomics technology and 250 differentially expressed proteins were screened in the GA group.Integrative analysis of mRNAmicroRNA-protein data showed that‘MAPK signaling pathway’was the key affected pathway after the function of integrin were interfered by GRGDS.Other seven pathways were also influenced,and the differentiation of PC12 cell grown on PLLA aligned nanofibers was finally inhibited.展开更多
Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require e...Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require extracellular matrix(ECM)-like features to better mimic the in vivo microenvironment.Consequently,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial NGCs.Heparin was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)nanofibers.Thereafter,basic fibroblast growth factor(bFGF)and nerve growth factor(NGF)were preferentially immobilized on heparinized nanofibers;the immobilization efficiency of GFs was found to be 50%with respect to(w.r.t.)their initial loaded amounts.The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention(~10%w.r.t the initial loaded amount)and bioactivity of NGF for up to 5 days.The permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate membranes.The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term(1 week)and long-term(1-month).The NGCs displayed good structural stability and biocompatibility in vivo.The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs.Taken together;these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.展开更多
The development of an ideal cathode for Li-O_(2)battery(LOB)has been a great challenge in achieving high discharge capacity,enhanced stability,and longevity.The formation of undesired and irreversible discharge produc...The development of an ideal cathode for Li-O_(2)battery(LOB)has been a great challenge in achieving high discharge capacity,enhanced stability,and longevity.The formation of undesired and irreversible discharge products on the surface of current cathode materials limit the life span of the LOB.In this study,we report the systematic electrochemical study to compare the performance of LOB employing a unique graphitic nanostructured carbon architecture,i.e.,vertically aligned carbon nanofiber(VACNF)arrays,as the cathode materials.Transition metal(Ni)and noble metal alloy(PtRu)are further deposited on the VACNF array as electrocatalysts to improve the discharge/charge processes at the cathode.The structure of as-prepared electrodes was examined with the field emission scanning electron microscopy,high-resolution transmission electron microscopy,and X-ray photoelectron spectroscopy(XPS).The LOB with VACNF-Ni electrode delivered the highest specific and areal discharge capacities(14.92 Ah·g^(−1),4.32 mAh·cm^(−2))at 0.1 mA·cm^(−2)current density as compared with VACNF-PtRu(9.07 Ah·g^(−1),2.62 mAh·cm^(−2)),bare VACNF(5.55 Ah·g^(−1),1.60 mAh·cm^(−2))and commercial Vulcan XC(3.83 Ah·g^(−1),1.91 mAh·cm^(−2)).Cycling stability tests revealed the superior performance of VACNF-PtRu with 27 cycles as compared with VACNF-Ni(13 cycles),VACNF(8 cycles),and Vulcan XC(3 cycles).The superior cycling stability of VACNF-PtRu can be attributed to its ability to suppress the formation of Li2CO3 during the discharge cycle,as elucidated by XPS analysis of discharged samples.We also investigated the impact of carbon cloth and carbon fiber as cathode electrode substrate on the performance of LOB.展开更多
Nanofiber networks are effective structural forms to utilize the excellent nanoscale properties of nanofibers in macro scale.Properly tuning the anisotropic degree of fiber orientation distribution can maximize the ma...Nanofiber networks are effective structural forms to utilize the excellent nanoscale properties of nanofibers in macro scale.Properly tuning the anisotropic degree of fiber orientation distribution can maximize the macroscopic mechanical properties of random nanofiber networks in a specific direction.However,the reinforcing mechanism of the anisotropic orientation distribution to the elastic behavior has not been fully understood.In this paper,the effect of anisotropic orientation distribution of nanofibers on the elastic behavior of network is studied based on the modulus-density scaling relation and stiffness thresholds.The uniaxial modulus of network is determined by both the orientation angle of each fiber and interconnectivity of the random fiber network.With the increase of anisotropic degree,the contribution of fiber orientation angle to the network modulus of the preferential direction increases and gradually tends to a constant,while the interconnectivity of the networks decreases,which may reduce the loadability of network.Therefore,at a given network density,the uniaxial modulus along the preferential direction first increases to a maximum value and then decreases with the increase of the anisotropic degree.Furthermore,an expression to predict the optimal anisotropic degrees corresponding to the maximum uniaxial moduli at different network densities is established.展开更多
The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell t...The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells.Herein,an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc(AFGN)was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair.The AFGN hydrogel provides multimodal cues,including oriented nanofibrous topography,soft stiffness,and specific cell binding ligand,for directing NSC functions and nerve regeneration.The conjugated N-Cadherin-Fc recapitulated the homo-philic cell-cell interaction for NSCs’adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation.In addition,the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention,immunomodulation,neuronal differentiation,and in vivo integration with inherent neurons,thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery.Altogether,this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche.展开更多
基金This work was supported by National Natural Science Foundation of China(31170910,31271012 and 31600816)the Natural Science Foundation of Jiangsu Province(BK20150599).
文摘The aim of this study is to unveil the role of integrin in influencing the differentiation of PC12 cell grown on PLLA aligned nanofibers by integrative study of cDNA microarray,proteomics technology and microRNA sequencing technology.First,PLLA-aligned nanofibers were prepared by electrospinning,and the chemical composition and surface morphology of the nanofibers were examined.Then,morphology and neurite length of PC12 cells and GRGDS-treated PC12 cells on PLLA-aligned nanofibers(AF and GA group)were measured by high-content analysis system.Subsequently,protein expression profile was analyzed by iTRAQ proteomics technology and 250 differentially expressed proteins were screened in the GA group.Integrative analysis of mRNAmicroRNA-protein data showed that‘MAPK signaling pathway’was the key affected pathway after the function of integrin were interfered by GRGDS.Other seven pathways were also influenced,and the differentiation of PC12 cell grown on PLLA aligned nanofibers was finally inhibited.
基金The part of this research was also funded by Grant-in-Aid for JSPS Fellows(Grant#JP21F21353)JSPS KAKENHI funding(JP18J20984 and JP21H01732).
文摘Injuries to the nervous system account for the widespread morbidity,mortality,and discomfort worldwide.Artificial nerve guidance conduits(NGCs)offer a promising platform for nerve reconstruction,however,they require extracellular matrix(ECM)-like features to better mimic the in vivo microenvironment.Consequently,this research was aimed to fabricate heparin/growth factors(GFs)-immobilized artificial NGCs.Heparin was covalently immobilized onto aligned electrospun polycapro-lactone/gelatin(PCL/Gel)nanofibers.Thereafter,basic fibroblast growth factor(bFGF)and nerve growth factor(NGF)were preferentially immobilized on heparinized nanofibers;the immobilization efficiency of GFs was found to be 50%with respect to(w.r.t.)their initial loaded amounts.The in vivo implantation of NGCs in a sciatic nerve defect model revealed the successful retention(~10%w.r.t the initial loaded amount)and bioactivity of NGF for up to 5 days.The permeability of bovine serum albumin(BSA)from nanofibrous membranes was further assessed and found to be comparable with the commercialized cel-lulose acetate membranes.The bioactivity of NGCs was assessed in a sciatic nerve defect model in rats for short-term(1 week)and long-term(1-month).The NGCs displayed good structural stability and biocompatibility in vivo.The in vivo evaluation revealed the accumulation of host cells into the transplanted NGCs.Taken together;these heparin/GFs-immobilized artificial NGCs may have broad implications for nerve regeneration and related tissue engineering disciplines.
基金S.S.H.Z.and X.L.L.highly appreciate the support from the National Science Foundation(Nos.1833048 and 1941083)The work by J.L.’s group is partially supported by the National Science Foundation under grant(No.CBET-2054754).
文摘The development of an ideal cathode for Li-O_(2)battery(LOB)has been a great challenge in achieving high discharge capacity,enhanced stability,and longevity.The formation of undesired and irreversible discharge products on the surface of current cathode materials limit the life span of the LOB.In this study,we report the systematic electrochemical study to compare the performance of LOB employing a unique graphitic nanostructured carbon architecture,i.e.,vertically aligned carbon nanofiber(VACNF)arrays,as the cathode materials.Transition metal(Ni)and noble metal alloy(PtRu)are further deposited on the VACNF array as electrocatalysts to improve the discharge/charge processes at the cathode.The structure of as-prepared electrodes was examined with the field emission scanning electron microscopy,high-resolution transmission electron microscopy,and X-ray photoelectron spectroscopy(XPS).The LOB with VACNF-Ni electrode delivered the highest specific and areal discharge capacities(14.92 Ah·g^(−1),4.32 mAh·cm^(−2))at 0.1 mA·cm^(−2)current density as compared with VACNF-PtRu(9.07 Ah·g^(−1),2.62 mAh·cm^(−2)),bare VACNF(5.55 Ah·g^(−1),1.60 mAh·cm^(−2))and commercial Vulcan XC(3.83 Ah·g^(−1),1.91 mAh·cm^(−2)).Cycling stability tests revealed the superior performance of VACNF-PtRu with 27 cycles as compared with VACNF-Ni(13 cycles),VACNF(8 cycles),and Vulcan XC(3 cycles).The superior cycling stability of VACNF-PtRu can be attributed to its ability to suppress the formation of Li2CO3 during the discharge cycle,as elucidated by XPS analysis of discharged samples.We also investigated the impact of carbon cloth and carbon fiber as cathode electrode substrate on the performance of LOB.
基金the National Natural Science Foundation of China[12002016,12172026,2225201]the National Key Research and Development Program of China[2020YFB1313003]+1 种基金China Postdoctoral Science Foundation[2020M680288]National Postdoctoral Program for Innovative Talents[BX20200032].
文摘Nanofiber networks are effective structural forms to utilize the excellent nanoscale properties of nanofibers in macro scale.Properly tuning the anisotropic degree of fiber orientation distribution can maximize the macroscopic mechanical properties of random nanofiber networks in a specific direction.However,the reinforcing mechanism of the anisotropic orientation distribution to the elastic behavior has not been fully understood.In this paper,the effect of anisotropic orientation distribution of nanofibers on the elastic behavior of network is studied based on the modulus-density scaling relation and stiffness thresholds.The uniaxial modulus of network is determined by both the orientation angle of each fiber and interconnectivity of the random fiber network.With the increase of anisotropic degree,the contribution of fiber orientation angle to the network modulus of the preferential direction increases and gradually tends to a constant,while the interconnectivity of the networks decreases,which may reduce the loadability of network.Therefore,at a given network density,the uniaxial modulus along the preferential direction first increases to a maximum value and then decreases with the increase of the anisotropic degree.Furthermore,an expression to predict the optimal anisotropic degrees corresponding to the maximum uniaxial moduli at different network densities is established.
基金National Natural Science Foundation of China(Grant Nos.32271414 and 82201521)Tsinghua Precision Medicine Foundation(Grant No.2022TS001)National Key Research and Development Program of China(Grant No.2020YFC1107600).
文摘The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells.Herein,an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc(AFGN)was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair.The AFGN hydrogel provides multimodal cues,including oriented nanofibrous topography,soft stiffness,and specific cell binding ligand,for directing NSC functions and nerve regeneration.The conjugated N-Cadherin-Fc recapitulated the homo-philic cell-cell interaction for NSCs’adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation.In addition,the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention,immunomodulation,neuronal differentiation,and in vivo integration with inherent neurons,thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery.Altogether,this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche.