Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their prog...Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their progression remains unclear.To date,neither animal experiments nor in vitro models have uncovered their early developmental characteristics caused by neuroinflammation.In this study,we developed a neurovascular-unit-on-a-chip(NVU-on-a-chip)to model inflammation-induced neurodevelopmental disorders.With the chip,dynamic visualization of the progression caused by neuroinflammation was clearly demonstrated,and the changes in angiogenesis and neural differentiation under neuroinflammation were replicated.In addition,the activation of astrocytes and damage to neurons and capillaries at the early stage of neurodevelopmental disorders were observed.The results revealed for the first time the structural disruption of the neurovascular units and the neurovascular coupling failure caused by neuroinflammation.Furthermore,the outcomes of anti-inflammatory intervention using ibuprofen were preliminarily demonstrated.This work provides insights into the early progression of neurodevelopmental disorders caused by neuroinflammation and offers a platform for the development of therapeutic strategies for neuroinflammation.展开更多
In cryopreservation,the addition of cryoprotectant can change the intra-and extra-cellular osmotic pressure,affect the cell morphology,and induce blebs on the plasma membrane.In this study,the blebs of cells microenca...In cryopreservation,the addition of cryoprotectant can change the intra-and extra-cellular osmotic pressure,affect the cell morphology,and induce blebs on the plasma membrane.In this study,the blebs of cells microencapsulated in the alginate microsphere induced by osmotic shock were studied,and the effects of microencapsulation on bleb size and cell viability were determined.Firstly,a coaxial co-flow focusing device was applied to generate cell-laden microcapsules using alginate hydrogel in this paper.Then,cellular blebs induced by DMSO with various concentrations under microencapsulation were compared with that when non-encapsulated,and the dynamic process of cellular bleb was investigated.Finally,the qualitative relationship between bleb size and cell viability in the presence of DMSO was built,and thus the effects of microencapsulation on bleb size and viability were evaluated.The results show that the bleb size is smaller and the cell viability is higher,and cell microencapsulation can significantly inhibit the excessively large blebs generated on the cell membrane and reduce the osmotic damage to cells when loading cryoprotectant and then to improve cell viability during cryopreservation.This work can provide insights for optimizing cryoprotectant-loading protocols,offer a new avenue to study cell blebbing,and advance future research on cryopreservation of rare cells and biomaterials.展开更多
Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus.However,the construction of hepatic sinusoids has always been a challenge for liver chips,especially for large-scal...Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus.However,the construction of hepatic sinusoids has always been a challenge for liver chips,especially for large-scale liver microsystems.Herein,we report an approach for the construction of hepatic sinusoids.In this approach,hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply.Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed.Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids,cell viability is witnessed to be considerably high,liver microstructure formation occurs,and hepatocyte metabolism is enhanced.In addition,this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing.This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.展开更多
基金supported by the National Key R&D Program of China(No.2018AAA0100300)the National Natural Science Foundation of China(Nos.82072018,82274375,and 82402490)+5 种基金the Anhui Provincial Science and Technology Major Project(No.202203a07020006)the Strategic Priority Research Program(C)of the Chinese Academy of Sciences(CAS)(No.XDC07040200)the Key R&D Program of Anhui Province(No.2022e07020012)the Natural Science Foundation of Anhui Province(No.2208085QH256)the Fundamental Research Funds for the Central Universities(No.WK2100000042)the China Postdoctoral Science Foundation(No.2022M713055).
文摘Neuroinflammation is the primary driver and signature of many neurodevelopmental disorders.However,because neurodevelopmental disorders caused by neuroinflammation are difficult to detect at the early stage,their progression remains unclear.To date,neither animal experiments nor in vitro models have uncovered their early developmental characteristics caused by neuroinflammation.In this study,we developed a neurovascular-unit-on-a-chip(NVU-on-a-chip)to model inflammation-induced neurodevelopmental disorders.With the chip,dynamic visualization of the progression caused by neuroinflammation was clearly demonstrated,and the changes in angiogenesis and neural differentiation under neuroinflammation were replicated.In addition,the activation of astrocytes and damage to neurons and capillaries at the early stage of neurodevelopmental disorders were observed.The results revealed for the first time the structural disruption of the neurovascular units and the neurovascular coupling failure caused by neuroinflammation.Furthermore,the outcomes of anti-inflammatory intervention using ibuprofen were preliminarily demonstrated.This work provides insights into the early progression of neurodevelopmental disorders caused by neuroinflammation and offers a platform for the development of therapeutic strategies for neuroinflammation.
基金partially supported by the National Natural Science Foundation of China (81571768)
文摘In cryopreservation,the addition of cryoprotectant can change the intra-and extra-cellular osmotic pressure,affect the cell morphology,and induce blebs on the plasma membrane.In this study,the blebs of cells microencapsulated in the alginate microsphere induced by osmotic shock were studied,and the effects of microencapsulation on bleb size and cell viability were determined.Firstly,a coaxial co-flow focusing device was applied to generate cell-laden microcapsules using alginate hydrogel in this paper.Then,cellular blebs induced by DMSO with various concentrations under microencapsulation were compared with that when non-encapsulated,and the dynamic process of cellular bleb was investigated.Finally,the qualitative relationship between bleb size and cell viability in the presence of DMSO was built,and thus the effects of microencapsulation on bleb size and viability were evaluated.The results show that the bleb size is smaller and the cell viability is higher,and cell microencapsulation can significantly inhibit the excessively large blebs generated on the cell membrane and reduce the osmotic damage to cells when loading cryoprotectant and then to improve cell viability during cryopreservation.This work can provide insights for optimizing cryoprotectant-loading protocols,offer a new avenue to study cell blebbing,and advance future research on cryopreservation of rare cells and biomaterials.
基金We acknowledge the funding support from the National Natural Science Foundation of China(82072018,81571768)the Anhui Provincial Natural Science Foundation(2208085QH256)+3 种基金the Strategic Priority Research Program(C)of the CAS(XDC07040200)the China Postdoctoral Science Foundation(2022M713055)the National Key Research and Development Program of China(2018AAA0100300)the Fundamental Research Funds for Central Universities(WK2480000006,WK9100000001,WK9110000125)。
文摘Hepatic sinusoids play a key role in maintaining high activities of liver cells in the hepatic acinus.However,the construction of hepatic sinusoids has always been a challenge for liver chips,especially for large-scale liver microsystems.Herein,we report an approach for the construction of hepatic sinusoids.In this approach,hepatic sinusoids are formed by demolding a self-developed microneedle array from a photocurable cell-loaded matrix in a large-scale liver-acinus-chip microsystem with a designed dual blood supply.Primary sinusoids formed by demolded microneedles and spontaneously self-organized secondary sinusoids can be clearly observed.Benefiting from significantly enhanced interstitial flows by formed hepatic sinusoids,cell viability is witnessed to be considerably high,liver microstructure formation occurs,and hepatocyte metabolism is enhanced.In addition,this study preliminarily demonstrates the effects of the resulting oxygen and glucose gradients on hepatocyte functions and the application of the chip in drug testing.This work paves the way for the biofabrication of fully functionalized large-scale liver bioreactors.
