The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body.In this paper,a novel modular microfluidic system with a vertical two-layered configuration is developed t...The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body.In this paper,a novel modular microfluidic system with a vertical two-layered configuration is developed to generate largescale perfused microvascular networks in vitro.The two-layer polydimethylsiloxane(PDMS)configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly.This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities.The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction,serving as the interface between the medium channels and tissue chambers.Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels.Various large-scale microvascular networks were generated and quantified in terms of vessel length and density.Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers.This platform enables the culturing of interconnected,large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications,including basic biological studies and drug screening.展开更多
基金supported by grants from the National Institutes of Health:UH3 TR00048 and UG3 HL141799-02the National Science Foundation:Center for Advanced Design and Manufacturing of Integrated Microfluidics(CADMIM)+4 种基金the National Natural Science Foundation of China(No.31600781 and No.61803250)the Science and Technology Commission of Shanghai Municipality(17JC1400202 and 19ZR1475000)the Shanghai Science and Technology Committee Rising-Star Program(No.19QA1403700)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2016 MS06)the Fundamental Research Funds for the Central Universities.
文摘The vascular network of the circulatory system plays a vital role in maintaining homeostasis in the human body.In this paper,a novel modular microfluidic system with a vertical two-layered configuration is developed to generate largescale perfused microvascular networks in vitro.The two-layer polydimethylsiloxane(PDMS)configuration allows the tissue chambers and medium channels not only to be designed and fabricated independently but also to be aligned and bonded accordingly.This method can produce a modular microfluidic system that has high flexibility and scalability to design an integrated platform with multiple perfused vascularized tissues with high densities.The medium channel was designed with a rhombic shape and fabricated to be semiclosed to form a capillary burst valve in the vertical direction,serving as the interface between the medium channels and tissue chambers.Angiogenesis and anastomosis at the vertical interface were successfully achieved by using different combinations of tissue chambers and medium channels.Various large-scale microvascular networks were generated and quantified in terms of vessel length and density.Minimal leakage of the perfused 70-kDa FITC-dextran confirmed the lumenization of the microvascular networks and the formation of tight vertical interconnections between the microvascular networks and medium channels in different structural layers.This platform enables the culturing of interconnected,large-scale perfused vascularized tissue networks with high density and scalability for a wide range of multiorgan-on-a-chip applications,including basic biological studies and drug screening.
