There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel m...There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.展开更多
The osteogenic differentiation and new bone formation are commonly delayed by bacterial infection of orthopedic implants,which is urgent to be resolved quickly in the clinic.The current paper prepared a strontium-dope...The osteogenic differentiation and new bone formation are commonly delayed by bacterial infection of orthopedic implants,which is urgent to be resolved quickly in the clinic.The current paper prepared a strontium-doped elec-trospinning fiber membrane with antibacterial and osteogenic properties by pulse electrochemical method.Poly-lactic acid/hydroxyapatite(PLLA/HA)composite fiber substrate was fabricated by electrospinning technology,and strontium doped SrHA/Cu/Polypyrrole(PPy)composite coating was constructed with pulse electrodeposi-tion method on its surface.The strontium doping technique,degradation of Sr^(2+)and Cu^(2+),cellular compatibility,and the antibacterial activity of the fiber membrane were examined.The results revealed that the deposition of phosphorus and calcium on composite fiber was the highest,indicating good biological activity.The release of Sr^(2+)and Cu^(2+)was stable and gradual due to the modulation of PPy.The composite fiber presented excellent antibacterial performance and the antibacterial rate was close to 100%against Staphylococcus aureus and Es-cherichia coli.Furthermore,it is conducive to the adhesion,spread,and proliferation of vascular endothelial cells and osteoblasts,namely outstanding osteogenesis and angiogenesis abilities.In conclusion,the multifunctional PLLA/HA@SrHA/Cu/PPy composite fiber membrane with good antibacterial and osteogenic activity by electro-spinning technology and pulsed electrochemical deposition method provides an effective strategy for the poor bone healing of infected bone defects.展开更多
基金funded by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52103174,52273133,and 82202686)+4 种基金the Shanghai Pujiang Program(2021PJD044)the Shanghai Municipal Heaith and Family Planning Commission(2022XD055)the China Postdoctoral Science Foundation(2022T150420 and 2022M712100)the Shanghai Jiading District Health Committee(2022-QN-05)the GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine.
文摘There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.
基金supported by the National Natural Science Founda-tion of China(Nos.52063027,81760397)Xinjiang Key Laboratory of Energy Storage and Photoelectroctalytic Materials,Autonomous Region graduate Innovation project(No.XJ2021G257)+1 种基金Outstanding Youth Nat-ural Science Foundation Project of Xinjiang(No.2021D01E16)Shanghai Municipal Health Commission(No.202140131).
文摘The osteogenic differentiation and new bone formation are commonly delayed by bacterial infection of orthopedic implants,which is urgent to be resolved quickly in the clinic.The current paper prepared a strontium-doped elec-trospinning fiber membrane with antibacterial and osteogenic properties by pulse electrochemical method.Poly-lactic acid/hydroxyapatite(PLLA/HA)composite fiber substrate was fabricated by electrospinning technology,and strontium doped SrHA/Cu/Polypyrrole(PPy)composite coating was constructed with pulse electrodeposi-tion method on its surface.The strontium doping technique,degradation of Sr^(2+)and Cu^(2+),cellular compatibility,and the antibacterial activity of the fiber membrane were examined.The results revealed that the deposition of phosphorus and calcium on composite fiber was the highest,indicating good biological activity.The release of Sr^(2+)and Cu^(2+)was stable and gradual due to the modulation of PPy.The composite fiber presented excellent antibacterial performance and the antibacterial rate was close to 100%against Staphylococcus aureus and Es-cherichia coli.Furthermore,it is conducive to the adhesion,spread,and proliferation of vascular endothelial cells and osteoblasts,namely outstanding osteogenesis and angiogenesis abilities.In conclusion,the multifunctional PLLA/HA@SrHA/Cu/PPy composite fiber membrane with good antibacterial and osteogenic activity by electro-spinning technology and pulsed electrochemical deposition method provides an effective strategy for the poor bone healing of infected bone defects.
