Effective osteogenesis remains a challenge in the treatment of bone defects.The emergence of artificial bone scaffolds provides an attractive solution.In this work,a new biomineralization strategy is proposed to facil...Effective osteogenesis remains a challenge in the treatment of bone defects.The emergence of artificial bone scaffolds provides an attractive solution.In this work,a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus(P),calcium(Ca),and silicon(Si).We developed black phosphorus(BP)-based,three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment.The fibrous scaffolds were fabricated from 3D poly(L-lactic acid)(PLLA)nanofibers(3D NFs),BP nanosheets,and hydroxyapatite(HA)-porous SiO2 nanoparticles.The 3D BP@HA NFs possess three advantages:i)stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells(BMSCs)into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis;ii)plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area;iii)the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation,thus achieving accelerated osteogenesis.Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs,with the assistance of NIR laser,exhibited good performance in promoting bone regeneration.Furthermore,microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs,rapid processing,high throughput and mass production,greatly improving the prospects for clinical application.This is also the first BP-based bone scaffold platform that can self-supply Ca^(2+),which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.展开更多
Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side eff...Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side effects.Furthermore,the apoptosis mechanism of tumor cells induced by celastrol has not been exhausted yet.In this study,we developed a reduction sensitive polymeric vector for tumor-targeted celastrol delivery.And our researches indicated that the celastrol could be delivered by reductionsensitive nanomedicine(RSNMs)with a controlled release strategy.Meanwhile,the cell uptake results indicated that excellent reduction-sensitive behavior of RSNMs could effectively accelerate celastrol into the human retinoblastoma(RB)cell.The cell cytotoxicity assay demonstrated that celastrol inhibited proliferation of human RB Y79 cells growth in a dose-dependent manner.Furthermore,the results of flow cytometry and terminal dUTP nick-end labeling(TUNEL)staining showed that celastrol induced apoptosis of the RB Y79 cells,and revealed a time-dependent increase in apoptosis induction of RB Y79 cells.The results of western blotting showed that celastrol induced the apoptosis of human RB Y79 cells involving the activation of caspase-3 and caspase-9.In conclusion,our results revealed that RSNMs may be utilized as a novel therapy for retinoblastoma.展开更多
基金the National Natural Science Foundation of China(U1904176,81600775,and 21504082to J.L.)+3 种基金Zhongyuan Thousand Talents Plan Project(to J.L.)Harvard Medical School/Brigham and Women’s Hospital Department of Anesthesiology-Basic Scientist Grant(2420 BPA075,to W.T.)Center for Nanomedicine Research Fund(2019A014810,to W.T.)Gillian Reny Stepping Strong Center for Trauma Innovation Breakthrough Innovator Award(113548,to W.T.).
文摘Effective osteogenesis remains a challenge in the treatment of bone defects.The emergence of artificial bone scaffolds provides an attractive solution.In this work,a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus(P),calcium(Ca),and silicon(Si).We developed black phosphorus(BP)-based,three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment.The fibrous scaffolds were fabricated from 3D poly(L-lactic acid)(PLLA)nanofibers(3D NFs),BP nanosheets,and hydroxyapatite(HA)-porous SiO2 nanoparticles.The 3D BP@HA NFs possess three advantages:i)stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells(BMSCs)into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis;ii)plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area;iii)the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation,thus achieving accelerated osteogenesis.Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs,with the assistance of NIR laser,exhibited good performance in promoting bone regeneration.Furthermore,microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs,rapid processing,high throughput and mass production,greatly improving the prospects for clinical application.This is also the first BP-based bone scaffold platform that can self-supply Ca^(2+),which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.
基金supported by the National Natural Science Foundation of China(Nos.81600775,U1904176 and 21504082)the Science and Technology Program of Henan Province,China(No.202102310072)the Medical Science and Technology Program of Henan Province,China(Nos.2018020398 and SB201902026)。
文摘Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side effects.Furthermore,the apoptosis mechanism of tumor cells induced by celastrol has not been exhausted yet.In this study,we developed a reduction sensitive polymeric vector for tumor-targeted celastrol delivery.And our researches indicated that the celastrol could be delivered by reductionsensitive nanomedicine(RSNMs)with a controlled release strategy.Meanwhile,the cell uptake results indicated that excellent reduction-sensitive behavior of RSNMs could effectively accelerate celastrol into the human retinoblastoma(RB)cell.The cell cytotoxicity assay demonstrated that celastrol inhibited proliferation of human RB Y79 cells growth in a dose-dependent manner.Furthermore,the results of flow cytometry and terminal dUTP nick-end labeling(TUNEL)staining showed that celastrol induced apoptosis of the RB Y79 cells,and revealed a time-dependent increase in apoptosis induction of RB Y79 cells.The results of western blotting showed that celastrol induced the apoptosis of human RB Y79 cells involving the activation of caspase-3 and caspase-9.In conclusion,our results revealed that RSNMs may be utilized as a novel therapy for retinoblastoma.