Breast cancer constitutes a significant global health burden,while conventional diagnosis approaches may lack precision and can be discomforting for patients.Exosomes have emerged as promising biomarkers for breast ca...Breast cancer constitutes a significant global health burden,while conventional diagnosis approaches may lack precision and can be discomforting for patients.Exosomes have emerged as promising biomarkers for breast cancer due to their participation in diverse pathological processes,and a convenient analysis platform is believed to greatly promote its application.In this study,we propose a novel digital PCR approach utilizing near-infrared(NIR)photo-responsive thermosensitive microcarriers integrated with black phosphorus for quantifying microRNA(miRNA)biomarkers within exosomes.Petal-like biomimetic nanomaterials were firstly assembled for nonspecific exosome capture based on the affinity effect of avidin and biotin.Photothermal-responsive microcarriers,fabricated using gelatin-based substrates blended with photothermal nanocomposite,exhibited NIRinduced heating and reversible phase transition properties.We optimized synthesis parameters on thermal response and established a programmable and controllable NIR light source module.The results indicated a significant elevation in the levels of biomarkers miRNA-1246 and miRNA-122,with fold increases ranging from 6.2 to 23.6 and 5.9 to 13.0,respectively,in breast cancer cell lines MCF-7 and MDA-MB-231 compared to healthy control cells HUVEC.This study offers broad prospects for utilizing exosomes to resolve predictive biomarkers.展开更多
Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this...Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II andβ-BAPN induced AAD models.Different from the single targeting therapeutic drug approaches,the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way.The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells,enhance M2 polarization of mouse bone marrow-derived macrophages,and reduce apoptosis of mouse aortic smooth muscle cells,but also regulate their interactions.The in vivo studies further confirm that silicate ions could effectively alleviate senescence,inflammation,and cell apoptosis of aortas,accomplished with reduced aortic dilation,collagen deposition,and elastin laminae degradation.This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.展开更多
Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorabl...Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorable.Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer.This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro,in particular hepatocellular carcinoma(HCC).Specifically,after introducing the current methods or techniques for preparing 3D in vitro liver cancer models,this review summarizes the relevant applications of these liver cancer models in vitro,e.g.drug screening,personalized medicine,and other applications.In the end,this review discusses the advantages and disadvantages of the liver cancer models in vitro,and proposes future prospects and research directions.展开更多
Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately.3D printing technology has attracted substantial attention for preparing penetrable multifunctional...Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately.3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration.Inspired by the spongy structure of natural bone,novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone(PLCL)and bioactive glass 45S5(BG),and polydopamine(PDA)was used to decorate the PLCL/BG scaffolds.The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured,and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo.The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity.The proliferation,adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups,which exhibited the best performance.The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration,which was further confirmed through immunohistochemical staining.Therefore,PDA decoration and the sustained release of bioactive ions(Ca,Si,P)from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis,which may provide a valuable basis for customized implants in extensive bone defect repair applications.展开更多
Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases.In this study,a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bi...Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases.In this study,a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis,regulating inflammation,and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases.In particular,sodium alginate,calcium silicate and strontium carbonate were used to prepare injectable hydrogels,which was gelled within 10 min.More importantly,this composite hydrogel sustainedly releases bioactive Sr^(2+)and SiO_(3)^(2-) ions within 28 days.The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs,SMCs,C2C12 and Raw 264.7 cells in vitro,and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo.The results showed that the composite hydrogel stimulated angiogenesis,developed new collateral capillaries,and re-established the blood supply.In addition,the bioactive hydrogel directly promoted the expression of muscle-regulating factors(MyoG and MyoD)to protect skeletal muscle from necrosis,inhibited M1 polarization,and promoted M2 polarization of macrophages to reduce inflammation,thereby protecting skeletal muscle cells and indirectly promoting vascularization.Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases.展开更多
The increased number of mastectomies,combined with rising patient expectations for cosmetic and psychosocial outcomes,has necessitated the use of adipose tissue restoration techniques.However,the therapeutic effect of...The increased number of mastectomies,combined with rising patient expectations for cosmetic and psychosocial outcomes,has necessitated the use of adipose tissue restoration techniques.However,the therapeutic effect of current clinical strategies is not satisfying due to the high demand of personalized customization and the timely vascularization in the process of adipose regeneration.Here,a composite hydrogel scaffold was prepared by three-dimensional(3D)printing technology,applying gelatin methacrylate anhydride(GelMA)as printing ink and calcium silicate(CS)bioceramic as an active ingredient for breast adipose tissue regeneration.The in vitro experiments showed that the composite hydrogel scaffolds could not only be customized with controllable architectures,but also significantly stimulated both 3T3-L1 preadipocytes and human umbilical vein endothelial cells in multiple cell behaviors,including cell adhesion,proliferation,migration and differentiation.Moreover,the composite scaffold promoted vascularized adipose tissue restoration under the skin of nude mice in vivo.These findings suggest that 3D-printed GelMA/CS composite scaffolds might be a good candidate for adipose tissue engineering.展开更多
基金National Key Research and Development Program of China,Grant/Award Number:2022YFA1405002National Natural Science Foundation of China,Grant/Award Numbers:12325405,22307098+6 种基金Wenzhou Institute,University of Chinese Academy of Sciences,Grant/Award Number:WIUCASQD2021012Wenzhou high‐level innovation teamDevelopment and application team of functional livKey Projects of Wenzhou Science and Technology Bureau,Grant/Award Number:ZG2023013Wenzhou Basic Research Projects,Grant/Award Number:Y2023147Zhejiang Provincial Natural Science Foundation of China,Grant/Award Number:LGF22C100003Key Laboratory of Structural Malformations in Children of Zhejiang Province,Grant/Award Number:ZJET2301Z。
文摘Breast cancer constitutes a significant global health burden,while conventional diagnosis approaches may lack precision and can be discomforting for patients.Exosomes have emerged as promising biomarkers for breast cancer due to their participation in diverse pathological processes,and a convenient analysis platform is believed to greatly promote its application.In this study,we propose a novel digital PCR approach utilizing near-infrared(NIR)photo-responsive thermosensitive microcarriers integrated with black phosphorus for quantifying microRNA(miRNA)biomarkers within exosomes.Petal-like biomimetic nanomaterials were firstly assembled for nonspecific exosome capture based on the affinity effect of avidin and biotin.Photothermal-responsive microcarriers,fabricated using gelatin-based substrates blended with photothermal nanocomposite,exhibited NIRinduced heating and reversible phase transition properties.We optimized synthesis parameters on thermal response and established a programmable and controllable NIR light source module.The results indicated a significant elevation in the levels of biomarkers miRNA-1246 and miRNA-122,with fold increases ranging from 6.2 to 23.6 and 5.9 to 13.0,respectively,in breast cancer cell lines MCF-7 and MDA-MB-231 compared to healthy control cells HUVEC.This study offers broad prospects for utilizing exosomes to resolve predictive biomarkers.
基金This work was supported by National Natural Science Foundation of China(82100427)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010203)the seed grants from the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCASQD2020013,WIUCASQD2021030),the founding from First Affiliated Hospital of Wenzhou Medical University.
文摘Aortic aneurysm and dissection(AAD)are leading causes of death in the elderly.Recent studies have demonstrated that silicate ions can manipulate multiple cells,especially vascular-related cells.We demonstrated in this study that silicate ions as soluble form of bioactive ceramics effectively alleviated aortic aneurysm and dissection in both Ang II andβ-BAPN induced AAD models.Different from the single targeting therapeutic drug approaches,the bioactive ceramic derived approach attributes to the effect of bioactive silicate ions on the inhibition of the AAD progression through regulating the local vascular microenvironment of aorta systematically in a multi-functional way.The in vitro experiments revealed that silicate ions did not only alleviate senescence and inflammation of the mouse aortic endothelial cells,enhance M2 polarization of mouse bone marrow-derived macrophages,and reduce apoptosis of mouse aortic smooth muscle cells,but also regulate their interactions.The in vivo studies further confirm that silicate ions could effectively alleviate senescence,inflammation,and cell apoptosis of aortas,accomplished with reduced aortic dilation,collagen deposition,and elastin laminae degradation.This bioactive ceramic derived therapy provides a potential new treatment strategy in attenuating AAD progression.
基金supported by the National Natural Science Foundation of China(Grant No.32101159)the WIUCAS’Startup Fund(Grant No.WIUCASQD2019007)+1 种基金the Youth Innovation Promotion Association of CAS(Grant No.2021007)the Engineering Research Center of Clin-ical Functional Materials and Diagnosis&Treatment Devices of Zhejiang Province(Grant No.WIUCASK19006).
文摘Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide.Although current advances in the treatment of liver cancer,the prognosis of this cancer remains unfavorable.Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer.This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro,in particular hepatocellular carcinoma(HCC).Specifically,after introducing the current methods or techniques for preparing 3D in vitro liver cancer models,this review summarizes the relevant applications of these liver cancer models in vitro,e.g.drug screening,personalized medicine,and other applications.In the end,this review discusses the advantages and disadvantages of the liver cancer models in vitro,and proposes future prospects and research directions.
基金support from Wenzhou Institute,University of Chinese Academy of Sciences(WIUCASQD2019002,WIUCASZZXF21005)the First Affiliated Hospital of Wenzhou Medical University.
文摘Large size bone defects affect human health and remain a worldwide health problem that needs to be solved immediately.3D printing technology has attracted substantial attention for preparing penetrable multifunctional scaffolds to promote bone reconditioning and regeneration.Inspired by the spongy structure of natural bone,novel porous degradable scaffolds have been printed using polymerization of lactide and caprolactone(PLCL)and bioactive glass 45S5(BG),and polydopamine(PDA)was used to decorate the PLCL/BG scaffolds.The physicochemical properties of the PLCL/BG and PLCL/BG/PDA scaffolds were measured,and their osteogenic and angiogenic effects were characterized through a series of experiments both in vitro and in vivo.The results show that the PLCL/BG2/PDA scaffold possessed a good compression modulus and brilliant hydrophilicity.The proliferation,adhesion and osteogenesis of hBMSCs were improved in the PDA coating groups,which exhibited the best performance.The results of the SD rat cranium defect model indicate that PLCL/BG2/PDA obviously promoted osteointegration,which was further confirmed through immunohistochemical staining.Therefore,PDA decoration and the sustained release of bioactive ions(Ca,Si,P)from BG in the 3D-printed PLCL/BG2/PDA scaffold could improve surface bioactivity and promote better osteogenesis and angiogenesis,which may provide a valuable basis for customized implants in extensive bone defect repair applications.
基金supported by the National Natural Science Foundation of China(grant number:82270415)Key Project Fund of Natural Science Foundation of Fujian Science and Technology Department(grant number:2021GGB030)+8 种基金Shanghai Municipal Science and Technology Commission Innovation Fund(grant number:22S31904800)Fudan Zhangjiang Clinical Medicine Innovation Fund(grant number:KP7202115)Fujian Province Health Science and Technology Fund(grant number:2021GGB030)the National Natural Science Foundation of China(grant number:81970412)Medical-Industrial Cooperation Project of Zhongshan Hospital Affiliated to Fudan University(grant number:MP2021Q2C018)National Clinical Research Center for Interventional Medicine Fund(grant number:2021-004)Xiamen Municipal Health Science And Technology Program Fund(grant number:3502Z20194034)Zhongshan hospital’s Talents Supporting Plan(grant number:2019ZSGG11)Shanghai Municipal Science and Technology Commission Innovation Fund(grant number:18441902400).
文摘Muscle necrosis and angiogenesis are two major challenges in the treatment of lower-limb ischemic diseases.In this study,a triple-functional Sr/Si-containing bioceramic/alginate composite hydrogel with simultaneous bioactivity in enhancing angiogenesis,regulating inflammation,and inhibiting muscle necrosis was designed to treat lower-limb ischemic diseases.In particular,sodium alginate,calcium silicate and strontium carbonate were used to prepare injectable hydrogels,which was gelled within 10 min.More importantly,this composite hydrogel sustainedly releases bioactive Sr^(2+)and SiO_(3)^(2-) ions within 28 days.The biological activity of the bioactive ions released from the hydrogels was verified on HUVECs,SMCs,C2C12 and Raw 264.7 cells in vitro,and the therapeutic effect of the hydrogel was confirmed using C57BL/6 mouse model of femoral artery ligation in vivo.The results showed that the composite hydrogel stimulated angiogenesis,developed new collateral capillaries,and re-established the blood supply.In addition,the bioactive hydrogel directly promoted the expression of muscle-regulating factors(MyoG and MyoD)to protect skeletal muscle from necrosis,inhibited M1 polarization,and promoted M2 polarization of macrophages to reduce inflammation,thereby protecting skeletal muscle cells and indirectly promoting vascularization.Our results indicate that these bioceramic/alginate composite bioactive hydrogels are effective biomaterials for treating hindlimb ischemia and suggest that biomaterial-based approaches may have remarkable potential in treating ischemic diseases.
基金supported by National Natural Science Foundation of China(32271386,31900945)Zhejiang Traditional Chinese Medicine Scientific Research Fund Project(2022ZB342)+3 种基金Chengdu Municipal Technological Innovation R&D Project(2021-YF05-01871-SN)Project of Chengdu Municipal Health Commission(2021059)the seed grants from the Wenzhou Institute,University of Chinese Academy of Sciences(WIUCASQD2020013,WIUCASQD2021030)the funding from First Affiliated Hospital of Wenzhou Medical University.
文摘The increased number of mastectomies,combined with rising patient expectations for cosmetic and psychosocial outcomes,has necessitated the use of adipose tissue restoration techniques.However,the therapeutic effect of current clinical strategies is not satisfying due to the high demand of personalized customization and the timely vascularization in the process of adipose regeneration.Here,a composite hydrogel scaffold was prepared by three-dimensional(3D)printing technology,applying gelatin methacrylate anhydride(GelMA)as printing ink and calcium silicate(CS)bioceramic as an active ingredient for breast adipose tissue regeneration.The in vitro experiments showed that the composite hydrogel scaffolds could not only be customized with controllable architectures,but also significantly stimulated both 3T3-L1 preadipocytes and human umbilical vein endothelial cells in multiple cell behaviors,including cell adhesion,proliferation,migration and differentiation.Moreover,the composite scaffold promoted vascularized adipose tissue restoration under the skin of nude mice in vivo.These findings suggest that 3D-printed GelMA/CS composite scaffolds might be a good candidate for adipose tissue engineering.
