The repair of bone defects relies on the intricate coordination of inflammation,angiogenesis,and osteogenesis.However,scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activ...The repair of bone defects relies on the intricate coordination of inflammation,angiogenesis,and osteogenesis.However,scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge.Here,a biomimetic scaffold(CHP@IC)with in situ PLGA@icariin(PLGA@IC)microspheres encapsulation was successfully fabricated using a one-step emulsification and poly-merization strategy.This approach not only simplifies the fabrication process but also ensures high encapsulation efficiency and sustained release of IC through PLGA@IC microspheres.The findings from subcutaneous im-plantation,network pharmacology-predicted molecular targets,and in vitro studies collectively reveal that the CHP@IC-induced M2 polarization of macrophages via STAT3 signaling pathway triggers the sequential activa-tion of inflammation,angiogenesis,and osteogenesis to enhance bone regeneration.The CHP@IC scaffold exhibited a significant osteogenic advantage in cranial defect repair,yielding new bone volumes approximately 3-fold and 10-fold greater than those in the CHP group and blank control group,respectively.This study not only elucidates the mechanism of IC in promoting regeneration of bone but also provides a novel method for designing scaffolds aimed at the efficient repair of bone defects.展开更多
Chiral nanomaterials have great potential for enhancing clinical therapeutic efficacy,attributed to the distinctive chiral selectivity in biosystems.Herein,we designed chiral iron singleatom nanoenzymes(L/D-Cys@SAFe/N...Chiral nanomaterials have great potential for enhancing clinical therapeutic efficacy,attributed to the distinctive chiral selectivity in biosystems.Herein,we designed chiral iron singleatom nanoenzymes(L/D-Cys@SAFe/NC)that exhibit remarkable tumor microenvironmenttriggered catalytic therapeutic activity,by simultaneously depleting GSH and generating potent reactive oxygen species in cancer cells.Under laser irradiation,they displays photothermal-enhanced catalytic activities.The study of L/D-Cys@SAFe/NC on cancer cells shows that D-Cys@SAFe/NC exhibits stronger cytotoxicity than L-Cys@SAFe/NC due to the stronger internalization ability,also supported by the higher efficiency of cancer therapy of D-Cys@SAFe/NC in vivo.This research demonstrates that the chirality of the surface ligand of the nanomaterials could exert a substantial impact on their efficacy in treating cancer,which opens a novel way for the advancement of anticancer nanomedicine.展开更多
Gentianae Radix et Rhizoma(also called "Longdan" in Chinese)is commonly used for eliminating damp-heat and quenching the fire of liver and gall bladder in traditional Chinese medicine.In this study,a novel a...Gentianae Radix et Rhizoma(also called "Longdan" in Chinese)is commonly used for eliminating damp-heat and quenching the fire of liver and gall bladder in traditional Chinese medicine.In this study,a novel and reliable method using high-performance liquid chromatography(HPLC)was developed both for quantitative analysis of four bioactive compounds(loganic acid,swertiamarin,gentiopicroside and sweroside)and chemical fingerprint analysis of "Longdan".In quantitative analysis,four compounds showed good regressions(R^(2)>40.9987)within the test ranges and the recovery of the method was in the range 97.61-102.49%.In fingerprint analysis,ten characteristic peaks were selected to evaluate the similarities of the crude drugs,and the HPLC chromatograms of twenty samples from different regions of China showed similar patterns.The results demonstrated that the combination of the quantitative and chromatographic fingerprint analyses offered an efficient way to evaluate the quality consistency of Gentianae Radix et Rhizoma.展开更多
In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,c...In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.展开更多
Extensive studies demonstrate that macrophage response plays an important role in regulating angiogenesis via a paracrine way,which is crucial for skin wound repair.This study isolated and characterized nanosized exos...Extensive studies demonstrate that macrophage response plays an important role in regulating angiogenesis via a paracrine way,which is crucial for skin wound repair.This study isolated and characterized nanosized exosomes from differently polarized macrophages(MΦ),including M0(naïve),M1(pro-inflammatory),and M2(anti-inflamma-tory)macrophages,and further assessed their impacts on angiogenesis and skin regeneration.Our results indicated that compared to M0 and M1 counterparts,M2 macrophage-derived exosomes(M2-Exos)exhibited a pronounced ability to promote angiogenic ability of of human umbilical vein endothelial cells(HUVECs)by enhancing expression of angiogenic genes and proteins,increasing cell migration,and improving tubulogenesis.Bioinformatics analyses suggested that the distinct angiogenic potentials of three MΦ-Exos might be attributed to the differentially expressed angiogenesis-related miRNAs and their target genes such as Stat3,Smad 2,and Smad4.Moreover,these isolated MΦ-Exos were integrated with gelatine methacrylate(GelMA)hydrogels to achieve the sustained delivery at murine full-thickness cutaneous wound sites.In vivo results showed that Gel/M2-Exos significantly augmented angiogenesis,accelerated re-epithelialization,promoted collagen maturity,thereby promoting wound healing.In contrary,Gel/M1-Exos showed the opposite effects.Our findings provided compelling evidence that the polarization status of mac-rophages significantly affected angiogenesis and wound healing via the miRNA cargos of their derived exosomes.Moreover,this study opens a new avenue for developing nano-scale,cell-free exosome-based therapies in treating cutaneous wounds.展开更多
基金supported by the Sichuan Science and Technology Program for Regional Innovation Cooperation,China(2024YFHZ0184)the Shenzhen Medical Research Fund(No.A2303016).
文摘The repair of bone defects relies on the intricate coordination of inflammation,angiogenesis,and osteogenesis.However,scaffolds capable of integrating osteo-immunomodulation and vascular-bone coupling to cascade-activate these processes remain a challenge.Here,a biomimetic scaffold(CHP@IC)with in situ PLGA@icariin(PLGA@IC)microspheres encapsulation was successfully fabricated using a one-step emulsification and poly-merization strategy.This approach not only simplifies the fabrication process but also ensures high encapsulation efficiency and sustained release of IC through PLGA@IC microspheres.The findings from subcutaneous im-plantation,network pharmacology-predicted molecular targets,and in vitro studies collectively reveal that the CHP@IC-induced M2 polarization of macrophages via STAT3 signaling pathway triggers the sequential activa-tion of inflammation,angiogenesis,and osteogenesis to enhance bone regeneration.The CHP@IC scaffold exhibited a significant osteogenic advantage in cranial defect repair,yielding new bone volumes approximately 3-fold and 10-fold greater than those in the CHP group and blank control group,respectively.This study not only elucidates the mechanism of IC in promoting regeneration of bone but also provides a novel method for designing scaffolds aimed at the efficient repair of bone defects.
基金supported by the National Natural Science Foundation of China(Nos.22075122 and 22371108)the Natural Science Foundation of Shandong Province(Nos.ZR2020QB170 and ZR2024MB125)Taishan Scholar Foundation of Shandong Province(No.tsqn202211242).
文摘Chiral nanomaterials have great potential for enhancing clinical therapeutic efficacy,attributed to the distinctive chiral selectivity in biosystems.Herein,we designed chiral iron singleatom nanoenzymes(L/D-Cys@SAFe/NC)that exhibit remarkable tumor microenvironmenttriggered catalytic therapeutic activity,by simultaneously depleting GSH and generating potent reactive oxygen species in cancer cells.Under laser irradiation,they displays photothermal-enhanced catalytic activities.The study of L/D-Cys@SAFe/NC on cancer cells shows that D-Cys@SAFe/NC exhibits stronger cytotoxicity than L-Cys@SAFe/NC due to the stronger internalization ability,also supported by the higher efficiency of cancer therapy of D-Cys@SAFe/NC in vivo.This research demonstrates that the chirality of the surface ligand of the nanomaterials could exert a substantial impact on their efficacy in treating cancer,which opens a novel way for the advancement of anticancer nanomedicine.
基金supported by Key National Science Foundation of China(81130069)Beijing Tongrentang Co.Ltd.(D08080203640901)the State Key Laboratory of Traditional Chinese Medicine Resources Research and Development in Chendu University of TCM。
文摘Gentianae Radix et Rhizoma(also called "Longdan" in Chinese)is commonly used for eliminating damp-heat and quenching the fire of liver and gall bladder in traditional Chinese medicine.In this study,a novel and reliable method using high-performance liquid chromatography(HPLC)was developed both for quantitative analysis of four bioactive compounds(loganic acid,swertiamarin,gentiopicroside and sweroside)and chemical fingerprint analysis of "Longdan".In quantitative analysis,four compounds showed good regressions(R^(2)>40.9987)within the test ranges and the recovery of the method was in the range 97.61-102.49%.In fingerprint analysis,ten characteristic peaks were selected to evaluate the similarities of the crude drugs,and the HPLC chromatograms of twenty samples from different regions of China showed similar patterns.The results demonstrated that the combination of the quantitative and chromatographic fingerprint analyses offered an efficient way to evaluate the quality consistency of Gentianae Radix et Rhizoma.
基金supported by the National Natural Science Foundation of China(Grant Nos.12202302,12272253,and 82103147)The support of the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province(Grant No.20220006)was also acknowledged with gratitude.
文摘In the field of bone defect repair,critical requirements for favorable cytocompatibility and optimal mechanical properties have propelled research efforts towards the development of composite materials.In this study,carbon nanotubes/polylactic acid/hydroxyapatite(CNTs/PLA/HA)scaffolds with different contents(0.5,1,1.5 and 2 wt.%)of CNTs were prepared by the thermally induced phase separation(TIPS)method.The results revealed that the composite scaffolds had uniform pores with high porosities over 68%and high through performances.The addition of CNTs significantly enhanced the mechanical properties of resulted PLA/HA,in which the 1.5 wt.%CNTs/PLA/HA composite scaffold demonstrated the optimum mechanical behaviors with the bending elastic modulus of(868.5±12.34)MPa,the tensile elastic modulus of(209.51±12.73)MPa,and the tensile strength of(3.26±0.61)MPa.Furthermore,L929 cells on the 1.5 wt.%CNTs/PLA/HA scaffold displayed good spreading performance and favorable cytocompatibility.Therefore,it is expected that the 1.5 wt.%CNTs/PLA/HA scaffold has potential applications in bone tissue engineering.
基金sponsored by the National Science Foundation of China(31971283,31670985)National Key Research and Development Program of China(2017YFB0702602)Sichuan Science and Technology Innova tion Team of China(2019JDTD0008).
文摘Extensive studies demonstrate that macrophage response plays an important role in regulating angiogenesis via a paracrine way,which is crucial for skin wound repair.This study isolated and characterized nanosized exosomes from differently polarized macrophages(MΦ),including M0(naïve),M1(pro-inflammatory),and M2(anti-inflamma-tory)macrophages,and further assessed their impacts on angiogenesis and skin regeneration.Our results indicated that compared to M0 and M1 counterparts,M2 macrophage-derived exosomes(M2-Exos)exhibited a pronounced ability to promote angiogenic ability of of human umbilical vein endothelial cells(HUVECs)by enhancing expression of angiogenic genes and proteins,increasing cell migration,and improving tubulogenesis.Bioinformatics analyses suggested that the distinct angiogenic potentials of three MΦ-Exos might be attributed to the differentially expressed angiogenesis-related miRNAs and their target genes such as Stat3,Smad 2,and Smad4.Moreover,these isolated MΦ-Exos were integrated with gelatine methacrylate(GelMA)hydrogels to achieve the sustained delivery at murine full-thickness cutaneous wound sites.In vivo results showed that Gel/M2-Exos significantly augmented angiogenesis,accelerated re-epithelialization,promoted collagen maturity,thereby promoting wound healing.In contrary,Gel/M1-Exos showed the opposite effects.Our findings provided compelling evidence that the polarization status of mac-rophages significantly affected angiogenesis and wound healing via the miRNA cargos of their derived exosomes.Moreover,this study opens a new avenue for developing nano-scale,cell-free exosome-based therapies in treating cutaneous wounds.
