Spinal cord injury(SCI)is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes,such as excessive reactive oxygen species(ROS)produced by the infiltrated ...Spinal cord injury(SCI)is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes,such as excessive reactive oxygen species(ROS)produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment,leading to the widespread apoptosis of the neuron cells,glial and oligodendroctyes.In this study,a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells(BMSCs),which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment.The hydrogel could effectively encapsulate BMSCs,and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS,attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α),resulting in a reduced cell apoptosis in the spinal cord tissue.The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation,and improved the neurogenesis of the spinal cord tissue,and thus distinctly enhanced the motor functional recovery of SCI rats.Our work provides a combinational strategy against ROS-mediated oxidative stress,with potential applications not only in SCI,but also in other central nervous system diseases with similar pathological conditions.展开更多
Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously ...Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far.In this study,a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly(D,L-lactide-co-caprolactone)(PLCL)guidance conduit and its advantages in regeneration of peripheral nerve in vivo.After linear ridges/grooves of 20/40μm in width are created on the PLCL film,its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups,which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde.The Schwann cells are better aligned along with the stripes,and show a faster migration rate toward the region of higher peptide density.Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate,function recovery and microstructures,and reduction of fibrosis in muscle tissues.Moreover,this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.展开更多
基金supported by the Natural Science Foundation of Zhejiang Province(LD21E030001)National Natural Science Foundation of China(51873188).
文摘Spinal cord injury(SCI)is an overwhelming and incurable disabling event accompanied by complicated inflammation-related pathological processes,such as excessive reactive oxygen species(ROS)produced by the infiltrated inflammatory immune cells and released to the extracellular microenvironment,leading to the widespread apoptosis of the neuron cells,glial and oligodendroctyes.In this study,a thioketal-containing and ROS-scavenging hydrogel was prepared for encapsulation of the bone marrow derived mesenchymal stem cells(BMSCs),which promoted the neurogenesis and axon regeneration by scavenging the overproduced ROS and re-building a regenerative microenvironment.The hydrogel could effectively encapsulate BMSCs,and played a remarkable neuroprotective role in vivo by reducing the production of endogenous ROS,attenuating ROS-mediated oxidative damage and downregulating the inflammatory cytokines such as interleukin-1 beta(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α),resulting in a reduced cell apoptosis in the spinal cord tissue.The BMSCs-encapsulated ROS-scavenging hydrogel also reduced the scar formation,and improved the neurogenesis of the spinal cord tissue,and thus distinctly enhanced the motor functional recovery of SCI rats.Our work provides a combinational strategy against ROS-mediated oxidative stress,with potential applications not only in SCI,but also in other central nervous system diseases with similar pathological conditions.
基金This study is financially supported by the National Key Research and Development Program of China(2016YFC1100403)the National Natural Science Foundation of China(21434006,51873188)and the Fundamental Research Funds for the Central Universities of China(2020XZZX004-01).
文摘Both of the surface topographical features and distribution of biochemical cues can influence the cell-substrate interactions and thereby tissue regeneration in vivo.However,they have not been combined simultaneously onto a biodegradable scaffold to demonstrate the synergistic role so far.In this study,a proof-of-concept study is performed to prepare micropatterns and peptide gradient on the inner wall of a poly(D,L-lactide-co-caprolactone)(PLCL)guidance conduit and its advantages in regeneration of peripheral nerve in vivo.After linear ridges/grooves of 20/40μm in width are created on the PLCL film,its surface is aminolyzed in a kinetically controlled manner to obtain the continuous gradient of amino groups,which are then transferred to CQAASIKVAV peptide density gradient via covalent coupling of glutaraldehyde.The Schwann cells are better aligned along with the stripes,and show a faster migration rate toward the region of higher peptide density.Implantation of the nerve guidance conduit made of the PLCL film having both the micropatterns and peptide gradient can significantly accelerate the regeneration of sciatic nerve in terms of rate,function recovery and microstructures,and reduction of fibrosis in muscle tissues.Moreover,this nerve conduit can also benefit the M2 polarization of macrophages and promote vascularization in vivo.