Existing numerical methods for complex composites, such as multiscale simulation and neural network algorithms, face significant limitations. Multiscale techniques are often prohibitively expensive for large models, w...Existing numerical methods for complex composites, such as multiscale simulation and neural network algorithms, face significant limitations. Multiscale techniques are often prohibitively expensive for large models, while neural networks struggle to represent underlying microscopic material properties. To overcome these challenges, a meso-micro scale numerical method using a virtual node approach is developed in this study. A Wbraid/Al/Epoxy functional structural material is fabricated, and a representative periodic unit cell is identified based on its architecture. The complex structure is then discretized into nodes, and mechanical interactions are governed by pre-defined computation rules. This virtual node method is systematically compared against both multiscale simulation and a neural network algorithm, with validation provided through mechanical experiments. The results demonstrate that the nodal operation strategy significantly reduces computational resource requirements. By quantifying microscopic bonding with coefficients, explicit interface treatment is avoided, granting the method strong adaptability to lattice materials. The method can simulate extremely complex structures using parameters from simple tests and is suited for large systems. Compared to three-point bending experiments, errors for multiscale, virtual node, and neural network methods were 12.4%, 6.9%, and 34.5%, respectively. Under dynamic compression, the errors were 2.7%, 9.3%, and 15.43%. The virtual node method demonstrated superior accuracy under static conditions, enabling efficient prediction and auxiliary development of complex structural materials.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disease that leads to joint deformities and functional impairments.Traditional treatment approaches,such as nonsteroidal anti-inflammatory drugs,disease-modifying antirh...Rheumatoid arthritis(RA)is a chronic autoimmune disease that leads to joint deformities and functional impairments.Traditional treatment approaches,such as nonsteroidal anti-inflammatory drugs,disease-modifying antirheumatic drugs,and molecular targeted therapies,often fail to simultaneously achieve efficient inflammation relief and cartilage tissue repair.DNA hydrogels,derived from nucleic acid nanotechnology,have demonstrated potential in RA therapy due to their programmability,high biocompatibility,and tunable degradation properties.However,their application is still hindered by challenges including high synthesis costs,immunogenicity risks,and uncontrolled degradation rates.To address these limitations,this study proposes a dual-action strategy involving a polymer-modified DNA hydrogel co-delivering nanozymes and living mitochondria to overcome the constraints of traditional therapies and comprehensively optimize RA treatment outcomes.The incorporation of functionalized polymers significantly reduces synthesis costs and immunogenicity while fine-tuning the degradation rate of the hydrogel,enabling sustained support during bone and cartilage repair.The hydrogel is loaded with Prussian blue nanozymes to scavenge excessive reactive oxygen species(ROS)within the RA microenvironment,alleviating inflammation,and facilitates intracellular delivery of living mitochondria to inhibit ROS production at its source,promoting tissue repair.By integrating endogenous ROS reduction with exogenous ROS clearance,this strategy markedly enhances therapeutic efficacy,offering a novel approach for precise RA treatment and advancing the clinical translation of biomaterials.展开更多
Osteoarthritis(OA),a common degenerative disease,is characterized by high disability and imposes substantial economic impacts on individuals and society.Current clinical treatments remain inadequate for effectively ma...Osteoarthritis(OA),a common degenerative disease,is characterized by high disability and imposes substantial economic impacts on individuals and society.Current clinical treatments remain inadequate for effectively managing OA.Organoids,miniature 3D tissue structures from directed differentiation of stem or progenitor cells,mimic native organ structures and functions.They are useful for drug testing and serve as active grafts for organ repair.However,organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth.Hydrogel microspheres,with tunable physical and chemical properties,show promise in cartilage tissue engineering by replicating the natural microenvironment.Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration,we developed a novel RGD-SF-DNA hydrogel microsphere(RSD-MS)via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA.The RSD-MSs exhibited uniform size,porous surface,and optimal swelling and degradation properties.In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells(BMSCs)proliferation,adhesion,and chondrogenic differentiation.Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis.Moreover,in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors(COPs)significantly enhanced cartilage regeneration.In conclusion,RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids,offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.展开更多
Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including s...Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including source scarcity and immune rejection risks.The advent of nucleic acid nanotechnology,particularly the use of DNA hydrogels in tissue engineering,presents a promising solution,attributed to their biocompatibility,biodegradability,and programmability.However,these hydrogels,typically hindered by high gelation temperatures(~46◦C)and high construction costs,limit cell encapsulation and broader application.Our research introduces a novel polymer-modified DNA hydrogel,developed using nucleic acid nanotechnology,which gels at a more biocompatible temperature of 37◦C and is cost-effective.This hydrogel then incorporates tetrahedral Framework Nucleic Acid(tFNA)to enhance osteogenic mineralization.Furthermore,considering the modifiability of tFNA,we modified its chains with Aptamer02(Apt02),an aptamer known to foster angiogenesis.This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs),with cell sequencing confirming their targeting efficacy,respectively.In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation.This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction,marking a significant advancement in tissue engineering and regenerative medicine.展开更多
Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,...Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.展开更多
Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues.Plant extrace...Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues.Plant extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive molecules.Due to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of AID.This review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in AID.Additionally,we propose engineering approaches and administration methods for PEVs.Finally,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of AID.By gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for AID.Natural and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.展开更多
文摘Existing numerical methods for complex composites, such as multiscale simulation and neural network algorithms, face significant limitations. Multiscale techniques are often prohibitively expensive for large models, while neural networks struggle to represent underlying microscopic material properties. To overcome these challenges, a meso-micro scale numerical method using a virtual node approach is developed in this study. A Wbraid/Al/Epoxy functional structural material is fabricated, and a representative periodic unit cell is identified based on its architecture. The complex structure is then discretized into nodes, and mechanical interactions are governed by pre-defined computation rules. This virtual node method is systematically compared against both multiscale simulation and a neural network algorithm, with validation provided through mechanical experiments. The results demonstrate that the nodal operation strategy significantly reduces computational resource requirements. By quantifying microscopic bonding with coefficients, explicit interface treatment is avoided, granting the method strong adaptability to lattice materials. The method can simulate extremely complex structures using parameters from simple tests and is suited for large systems. Compared to three-point bending experiments, errors for multiscale, virtual node, and neural network methods were 12.4%, 6.9%, and 34.5%, respectively. Under dynamic compression, the errors were 2.7%, 9.3%, and 15.43%. The virtual node method demonstrated superior accuracy under static conditions, enabling efficient prediction and auxiliary development of complex structural materials.
基金financially supported by National Natural Science Foundation of China(32471396,82230071,82172098)Shanghai Committee of Science and Technology(23141900600,Laboratory Animal Research Project)+3 种基金Shanghai Clinical Research Plan of SHDC2023CRT01Shanghai Municipal Demonstration Project for Innovative Medical Device Applications(23SHS05700)Young Elite Scientist Sponsorship Program by China Association for Science and Technology(YESS20230049)Key Project of the Seed Program for Medical New Technology Research and Translation of the Shanghai Municipal Health Commission(2024ZZ1001).
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that leads to joint deformities and functional impairments.Traditional treatment approaches,such as nonsteroidal anti-inflammatory drugs,disease-modifying antirheumatic drugs,and molecular targeted therapies,often fail to simultaneously achieve efficient inflammation relief and cartilage tissue repair.DNA hydrogels,derived from nucleic acid nanotechnology,have demonstrated potential in RA therapy due to their programmability,high biocompatibility,and tunable degradation properties.However,their application is still hindered by challenges including high synthesis costs,immunogenicity risks,and uncontrolled degradation rates.To address these limitations,this study proposes a dual-action strategy involving a polymer-modified DNA hydrogel co-delivering nanozymes and living mitochondria to overcome the constraints of traditional therapies and comprehensively optimize RA treatment outcomes.The incorporation of functionalized polymers significantly reduces synthesis costs and immunogenicity while fine-tuning the degradation rate of the hydrogel,enabling sustained support during bone and cartilage repair.The hydrogel is loaded with Prussian blue nanozymes to scavenge excessive reactive oxygen species(ROS)within the RA microenvironment,alleviating inflammation,and facilitates intracellular delivery of living mitochondria to inhibit ROS production at its source,promoting tissue repair.By integrating endogenous ROS reduction with exogenous ROS clearance,this strategy markedly enhances therapeutic efficacy,offering a novel approach for precise RA treatment and advancing the clinical translation of biomaterials.
基金supported by the National Key Research and Development Program of China(No.2022YFB3804300)Integrated Project of Major Research Plan of National Natural Science Foundation of China(92249303)+1 种基金Key Project of the National Natural Science Foundation of China(82230071)National Natural Science Foundation of China(32101084).
文摘Osteoarthritis(OA),a common degenerative disease,is characterized by high disability and imposes substantial economic impacts on individuals and society.Current clinical treatments remain inadequate for effectively managing OA.Organoids,miniature 3D tissue structures from directed differentiation of stem or progenitor cells,mimic native organ structures and functions.They are useful for drug testing and serve as active grafts for organ repair.However,organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth.Hydrogel microspheres,with tunable physical and chemical properties,show promise in cartilage tissue engineering by replicating the natural microenvironment.Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration,we developed a novel RGD-SF-DNA hydrogel microsphere(RSD-MS)via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA.The RSD-MSs exhibited uniform size,porous surface,and optimal swelling and degradation properties.In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells(BMSCs)proliferation,adhesion,and chondrogenic differentiation.Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis.Moreover,in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors(COPs)significantly enhanced cartilage regeneration.In conclusion,RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids,offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.
基金supported by National Natural Science Foundation of China(82230071,82172098)Integrated Project of Major Research Plan of National Natural Science Foundation of China(92249303)+1 种基金Shanghai Committee of Science and Technology(23141900600,Laboratory Animal Research Project)Shanghai Clinical Research Plan of SHDC2023CRT01.
文摘Segmental bone defects,stemming from trauma,infection,and tumors,pose formidable clinical challenges.Traditional bone repair materials,such as autologous and allogeneic bone grafts,grapple with limitations including source scarcity and immune rejection risks.The advent of nucleic acid nanotechnology,particularly the use of DNA hydrogels in tissue engineering,presents a promising solution,attributed to their biocompatibility,biodegradability,and programmability.However,these hydrogels,typically hindered by high gelation temperatures(~46◦C)and high construction costs,limit cell encapsulation and broader application.Our research introduces a novel polymer-modified DNA hydrogel,developed using nucleic acid nanotechnology,which gels at a more biocompatible temperature of 37◦C and is cost-effective.This hydrogel then incorporates tetrahedral Framework Nucleic Acid(tFNA)to enhance osteogenic mineralization.Furthermore,considering the modifiability of tFNA,we modified its chains with Aptamer02(Apt02),an aptamer known to foster angiogenesis.This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs),with cell sequencing confirming their targeting efficacy,respectively.In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation.This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction,marking a significant advancement in tissue engineering and regenerative medicine.
基金supported by the National Key Research and Development Plan(2018YFC2001500)National Natural Science Foundation of China(81972254,82172098).
文摘Skeletal muscle disorders have posed great threats to health.Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging.Aptamers can improve targeting efficacy.In this study,for the first time,the human skeletal muscle-specific ssDNA aptamers(HSM01,etc.)were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment(SELEX).The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro.The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells.Furthermore,the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo,suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes.Therefore,this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.
基金supported by the National Natural Science Foundation of China(Nos.82230071,and 82202344)Integrated Project of Major Research Plan of National Natural Science Foundation of China(No.92249303)Shanghai Committee of Science and Technology Laboratory Animal Research Project(No.23141900600).
文摘Autoimmune diseases(AID)encompass a diverse array of conditions characterized by immune system dysregulation,resulting in aberrant responses of B cells and T cells against the body’s own healthy tissues.Plant extracellular vesicles(PEVs)are nanoscale particles enclosed by phospholipid bilayers,secreted by plant cells,which facilitate intercellular communication by transporting various bioactive molecules.Due to their nanoscale structure,safety,abundant sources,low immunogenicity,high yield,biocompatibility,and effective targeting of the colon and liver,PEVs are regarded as a promising platform for the treatment of AID.This review provides a comprehensive summary of PEV biogenesis,physicochemical and biological properties,internalization mechanisms,isolation methods,and their applications in various diseases,with a specific focus on their potential roles in AID.Additionally,we propose engineering approaches and administration methods for PEVs.Finally,we present an overview of the advantages and challenges associated with utilizing PEVs for the treatment of AID.By gaining a comprehensive understanding of PEVs,we anticipate the development of innovative therapeutic strategies for AID.Natural and engineered PEVs hold substantial promise as a valuable resource for innovative technologies in AID treatment.
