Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that M...Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.展开更多
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
基金supported by grants from the National Natural Science Foundation of China(82474093,81973536)Jiangsu Province“Blue and Green Project”(184080H10240)+2 种基金Graduate Research Innovation Program of Jiangsu(KYCX23_0871)the National Natural Science Foundation of the Youth Science Fund Project(81703775)Health Research Program of Wuxi Municipal Health Commission(Q202107).
文摘Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.
