Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular mat...Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.展开更多
Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedica...Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.展开更多
Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering t...Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering the absence of targeting propulsion capability.Here,encouraged by the fast-developing controllable microrobotics for targeting delivery,a sunflower-like nanocatalytic active swarm(SNCAS)controlled by a three-dimensional(3D)magnetic field was proposed for synergistic tumorselective and magnetic-actively tumor-targeting therapeutics.Furthermore,a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes.Under the targeted control of 3D magnetic field,the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated,resulting in efficient tumor cell apoptosis and death.For the patient-derived organoid treatment,the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology.The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS.Overall,empowered by the magnetic control technology,the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy.Meanwhile,3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine.展开更多
Tailpipe emissions from light-duty gasoline vehicles usually deteriorate over time. The accumulation of engine deposits due to inadequate gasoline detergency is considered to be one of the major causes of such emissio...Tailpipe emissions from light-duty gasoline vehicles usually deteriorate over time. The accumulation of engine deposits due to inadequate gasoline detergency is considered to be one of the major causes of such emission deterioration. Six in-use light-duty gasoline vehicles in Beijing were tested to investigate the impact of engine deposits on emissions of hydrocarbons （HC）, carbon monoxide （CO） and nitrogen oxides （NOx）. Emissions under cold start and hot running test conditions from the six light duty vehicles were measured before and after engine deposits were removed. Results show that although individual vehicles reacted differently for each of the pollutants, elimination of engine deposits on average reduced HC emissions under hot running conditions by 29.4%, CO emissions under cold start conditions by 23.0% and CO emissions under hot running conditions by 35.5% （t 〈 0.05 in all cases）. No pollutant emissions increased with statistical significance （t 〈 0.05） after the removal of engine deposits. Variations of emission changes upon removal of engine deposits were observed. Such variations are in line with previous studies, implying that the impact patterns of engine deposits on vehicle emissions may be subject to many influencing factors that are not fully understood and difficult to control under all conditions. A statistical view of the impact of engine deposits on vehicle emissions may be appropriate for evaluation of emissions reductions across a city or a country. It is necessary to maintain sufficient and effective gasoline fuel detergency in practice to keep the engines clean and in tum reduce vehicle emissions.展开更多
Increasing lung diseases,mutating coronaviruses,and the development of new compounds urgently require biomimetic in vitro lung models for lung pathology,toxicology,and pharmacology.The current construction strategies ...Increasing lung diseases,mutating coronaviruses,and the development of new compounds urgently require biomimetic in vitro lung models for lung pathology,toxicology,and pharmacology.The current construction strategies for lung models mainly include animal models,2D cell culture,lung-on-a-chip,and lung organoids.However,current models face difficulties in reproducing in vivo-like alveolar size and vesicle-like structures,and are unable to contain multiple cell types.In this study,a strategy for constructing alveolar models based on degradable hydrogel microspheres is proposed.Hydrogel microspheres,200-250μm in diameter,were prepared using a self-developed printing technique driven by alternating viscous and inertial forces.Microcapsules were further constructed using a coacervation-based layer-by-layer technique and core liquefaction.Three types of cells were inoculated and co-cultured on hydrogel capsules based on optimized microcapsule surface treatment strategies.Finally,an in vitro three-dimensional endothelial alveolar model with a multicellular composition and vesicle-like structure with a diameter of approximately 230μm was successfully constructed.Cells in the constructed alveolar model maintained a high survival rate.The LD_(50)values of glutaraldehyde based on the constructed models were in good agreement with the reference values,validating the potential of the model for future toxicant and drug detection.展开更多
文摘Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.
文摘Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.
基金This work was supported by the National Key R&D Program of China(No.2018YFA0901700)the National Natural Science Foundation of China(Nos.21878173,52175273,and 82072837)+1 种基金the 111 Project(No.B17026)a grant from the Institute Guo Qiang,Tsinghua University(No.2021GQG1016).
文摘Nanocatalytic medicine triggering in situ catalytic reactions has been considered as a promising strategy for tumor-selective therapeutics.However,the targeted distribution of nanocatalysts was still low,considering the absence of targeting propulsion capability.Here,encouraged by the fast-developing controllable microrobotics for targeting delivery,a sunflower-like nanocatalytic active swarm(SNCAS)controlled by a three-dimensional(3D)magnetic field was proposed for synergistic tumorselective and magnetic-actively tumor-targeting therapeutics.Furthermore,a patient-derived renal cancer cell 3D organoid was utilized for the verification of the effective tumor therapeutic outcomes.Under the targeted control of 3D magnetic field,the multiple cascade catalytic efficiency of SNCAS based on Fenton reaction was evaluated,resulting in efficient tumor cell apoptosis and death.For the patient-derived organoid treatment,the SNCAS presented significant lethality toward 3D organoid structure to induce cell apoptosis with the collapse of organoid morphology.The targeting efficiency was further enhanced under the magnetic-controllable of SNCAS.Overall,empowered by the magnetic control technology,the synergistic therapeutic strategy based on controllable swarm combined active targeting and tumor-specific catalytic nanomedicine has provided a novel way for advanced cancer therapy.Meanwhile,3D patient-derived organoids were proved as a powerful tool for the effectiveness verification of nanocatalytic medicine.
文摘Tailpipe emissions from light-duty gasoline vehicles usually deteriorate over time. The accumulation of engine deposits due to inadequate gasoline detergency is considered to be one of the major causes of such emission deterioration. Six in-use light-duty gasoline vehicles in Beijing were tested to investigate the impact of engine deposits on emissions of hydrocarbons （HC）, carbon monoxide （CO） and nitrogen oxides （NOx）. Emissions under cold start and hot running test conditions from the six light duty vehicles were measured before and after engine deposits were removed. Results show that although individual vehicles reacted differently for each of the pollutants, elimination of engine deposits on average reduced HC emissions under hot running conditions by 29.4%, CO emissions under cold start conditions by 23.0% and CO emissions under hot running conditions by 35.5% （t 〈 0.05 in all cases）. No pollutant emissions increased with statistical significance （t 〈 0.05） after the removal of engine deposits. Variations of emission changes upon removal of engine deposits were observed. Such variations are in line with previous studies, implying that the impact patterns of engine deposits on vehicle emissions may be subject to many influencing factors that are not fully understood and difficult to control under all conditions. A statistical view of the impact of engine deposits on vehicle emissions may be appropriate for evaluation of emissions reductions across a city or a country. It is necessary to maintain sufficient and effective gasoline fuel detergency in practice to keep the engines clean and in tum reduce vehicle emissions.
基金supported by Beijing Municipal Natural Science Foundation of China(Grant No.3212007)Tsinghua University Spring Breeze Fund(Grant No.20201080760)+2 种基金Tsinghua University Ini-tiative Scientific Research Program(Grant No.20213080030)Na-tional Key Research and Development Program of China(Grant No.2018YFA0703004)National Natural Science Foundation of China(Grant No.52175273),and 111 Project(Grant No.B17026).
文摘Increasing lung diseases,mutating coronaviruses,and the development of new compounds urgently require biomimetic in vitro lung models for lung pathology,toxicology,and pharmacology.The current construction strategies for lung models mainly include animal models,2D cell culture,lung-on-a-chip,and lung organoids.However,current models face difficulties in reproducing in vivo-like alveolar size and vesicle-like structures,and are unable to contain multiple cell types.In this study,a strategy for constructing alveolar models based on degradable hydrogel microspheres is proposed.Hydrogel microspheres,200-250μm in diameter,were prepared using a self-developed printing technique driven by alternating viscous and inertial forces.Microcapsules were further constructed using a coacervation-based layer-by-layer technique and core liquefaction.Three types of cells were inoculated and co-cultured on hydrogel capsules based on optimized microcapsule surface treatment strategies.Finally,an in vitro three-dimensional endothelial alveolar model with a multicellular composition and vesicle-like structure with a diameter of approximately 230μm was successfully constructed.Cells in the constructed alveolar model maintained a high survival rate.The LD_(50)values of glutaraldehyde based on the constructed models were in good agreement with the reference values,validating the potential of the model for future toxicant and drug detection.
