Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-e...Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.展开更多
With the advent of tissue engineering and biomedicine,the creation of extracellular matrix(ECM)biomaterials for in vitro applications has become a prominent and promising strategy.These ECM materials provide physical,...With the advent of tissue engineering and biomedicine,the creation of extracellular matrix(ECM)biomaterials for in vitro applications has become a prominent and promising strategy.These ECM materials provide physical,biochemical,and mechanical properties that guide cellular behaviors,such as proliferation,differentiation,migration,and apoptosis.Because micro-and nano-patterned materials have a unique surface topology and low energy replication process that directly affect cellular biological behaviors at the interface,the fabrication of micro-nano pattern biomaterials and the regulation of surface physical and chemical properties are of great significance in the fields of cell regulation,tissue engineering,and regenerative medicine.Herein,we provide a comprehensive review of the progress in the fabrication and application of patterned materials based on the coupling of mechanical action at the micro-and nano-meter scale,including photolithography,micro-contact printing,electron beam lithography,electrospinning,and 3D printing technology.Furthermore,a summary of the fabrication process,underlying principles,as well as the advantages and disadvantages of various technologies are reviewed.We also discuss the influence of material properties on the fabrication of micro-and nano-patterns.展开更多
基金supported by the National Natural Science Foundation of China, Nos.81971151 (to YW), 82102528 (to XL), 82102583 (to LW)the Natural Science Foundation of Guangdong Province, China, Nos.2020A1515010265 (to YW), 2020A1515110679 (to XL), and 2021A1515010358 (to XL)
文摘Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury.Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction.However,the mechanisms involved remain unclear.In this study,we found that after spinal cord injury,resting microglia(M0)were polarized into pro-inflammatory phenotypes(MG1 and MG3),while resting astrocytes were polarized into reactive and scar-forming phenotypes.The expression of growth arrest-specific 6(Gas6)and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury.In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia,and even inhibited the cross-regulation between them.We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway.This,in turn,inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways.In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord,thereby promoting tissue repair and motor function recovery.Overall,Gas6 may play a role in the treatment of spinal cord injury.It can inhibit the inflammatory pathway of microglia and polarization of astrocytes,attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment,and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
基金supported by Key Research Program of Frontier Sciences of CAS(No.QYKJZD-SSW-SLH02).
文摘With the advent of tissue engineering and biomedicine,the creation of extracellular matrix(ECM)biomaterials for in vitro applications has become a prominent and promising strategy.These ECM materials provide physical,biochemical,and mechanical properties that guide cellular behaviors,such as proliferation,differentiation,migration,and apoptosis.Because micro-and nano-patterned materials have a unique surface topology and low energy replication process that directly affect cellular biological behaviors at the interface,the fabrication of micro-nano pattern biomaterials and the regulation of surface physical and chemical properties are of great significance in the fields of cell regulation,tissue engineering,and regenerative medicine.Herein,we provide a comprehensive review of the progress in the fabrication and application of patterned materials based on the coupling of mechanical action at the micro-and nano-meter scale,including photolithography,micro-contact printing,electron beam lithography,electrospinning,and 3D printing technology.Furthermore,a summary of the fabrication process,underlying principles,as well as the advantages and disadvantages of various technologies are reviewed.We also discuss the influence of material properties on the fabrication of micro-and nano-patterns.
