Osteoarthritis(OA),a common disabling joint disease,is highly associated with microenvironmental changes in the cartilage and subchondral bone.Elevated reactive oxygen species(ROS)in the cartilage and subchondral bone...Osteoarthritis(OA),a common disabling joint disease,is highly associated with microenvironmental changes in the cartilage and subchondral bone.Elevated reactive oxygen species(ROS)in the cartilage and subchondral bone angiogenesis accelerate articular cartilage erosion.New cartilage-targeting drug deliv-ery systems that are aimed at preventing ROS production and angiogenesis may be of clinical significance for OA treatment.Herein,an ROS scavenger and an inflammatory-responsive nanocarrier are designed by immobilizing the natural polyphenol(curcumin)in chitosan-catechol nanoformulations(Cur-CS-C NPs)via boronate ester.The robust cartilage-targeting effects and ROS scavenging capacities of Cur-CS-C NPs were respectively determined in cartilage explants and chondrocytes.Intra-articular injection of Cur-CS-C NPs in OA rat models efficiently suppressed angiogenesis and cartilage degradation partially via the ROS-mediated NF-κB/PI3K-Akt signaling pathway.The developed curcumin-functionalized nanocarriers can significantly delay OA progression and provide a promising therapeutic strategy for other inflamma-tory diseases that are characterized by oxidative stress and angiogenesis.展开更多
The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making...The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.展开更多
基金financially supported by the National Natural Science Foundation of China (Nos.11532004 and 11832008)the Innovation and Attracting Talents Program for College and Univer-sity (“111”Project) (No.B06023).
文摘Osteoarthritis(OA),a common disabling joint disease,is highly associated with microenvironmental changes in the cartilage and subchondral bone.Elevated reactive oxygen species(ROS)in the cartilage and subchondral bone angiogenesis accelerate articular cartilage erosion.New cartilage-targeting drug deliv-ery systems that are aimed at preventing ROS production and angiogenesis may be of clinical significance for OA treatment.Herein,an ROS scavenger and an inflammatory-responsive nanocarrier are designed by immobilizing the natural polyphenol(curcumin)in chitosan-catechol nanoformulations(Cur-CS-C NPs)via boronate ester.The robust cartilage-targeting effects and ROS scavenging capacities of Cur-CS-C NPs were respectively determined in cartilage explants and chondrocytes.Intra-articular injection of Cur-CS-C NPs in OA rat models efficiently suppressed angiogenesis and cartilage degradation partially via the ROS-mediated NF-κB/PI3K-Akt signaling pathway.The developed curcumin-functionalized nanocarriers can significantly delay OA progression and provide a promising therapeutic strategy for other inflamma-tory diseases that are characterized by oxidative stress and angiogenesis.
基金supported financially by the National Natural Science Foundation of China[No.11532004,11832008]Innovation and Attracting Talents Program for College and University(“111”Project)[No.B06023]。
文摘The presence of excessive reactive oxygen species(ROS)after injuries to the enthesis could lead to cellular oxidative damage,high inflammatory response,chronic inflammation,and limited fibrochondral inductivity,making tissue repair and functional recovery difficult.Here,a multifunctional silk fibroin nanofiber modified with polydopamine and kartogenin was designed and fabricated to not only effectively reduce inflammation by scavenging ROS in the early stage of the enthesis healing but also enhance fibrocartilage formation with fibrochondrogenic induction in the later stages.The in vitro results confirmed the antioxidant capability and the fibrochondral inductivity of the functionalized nanofibers.In vivo studies showed that the multifunctional nanofiber can significantly improve the integration of tendon-bone and accelerate the regeneration of interface tissue,resulting in an excellent biomechanical property.Thus,the incorporation of antioxidant and bio-active molecules into extracellular matrix-like biomaterials in interface tissue engineering provides an integrative approach that facilitates damaged tissue regeneration and functional recovery,thereby improving the clinical outcome of the engineered tissue.
