Effective treatment of intervertebral disc degeneration with biomaterials remains a challenge,owing to the difficulty in simultaneously overcoming oxidative stress and its associated cascades in the nucleus pulposus m...Effective treatment of intervertebral disc degeneration with biomaterials remains a challenge,owing to the difficulty in simultaneously overcoming oxidative stress and its associated cascades in the nucleus pulposus microenvironment,which includes cellular senescence,apoptosis,inflammation,and extracellular matrix(ECM)degradation.To address these issues,a multifunctional hydrogel(HG-QNT)loaded with transforming growth factorβ1(TGFβ1)and quercetin-based nanoparticles(QUNPs)is developed through borate ester bonding and Schiffbase reaction-induced crosslinking.Specifically,QUNPs fabricated via coordination and hydrophobic interactions endow the hydrogel with extraordinary antioxidative properties.Benefiting from the multi-dynamic crosslinking,the hydrogel achieves self-healing,mechanical stability,and pH-responsive release of QUNPs and TGFβ1.The HG-QNT hydrogel is demonstrated to enhance the proliferation of encapsulated nucleus pulposus cells,thereby providing an ideal platform for cell transplantation.The cooperative antioxidation of QUNPs and the hydrogel carrier renders HG-QNT effective in mitigating oxidative stress,resulting in the suppression of cellular senescence,mitochondrial dysfunction,apoptosis,excessive inflammation,and abnormal catabolism.Afterwards,TGFβ1 and QUNPs act in synergy with the hydrogel to restore the anabolic/catabolic balance by enhancing ECM synthesis.Overall,the strategy orchestrating multiple modulation by HG-QNT hydrogel shows great potential for application in intervertebral disc regeneration.展开更多
基金supported by the National Natural Science Foun-dation of China(Grant No.52073103,52272276,51873069,and 52373128)Beijing Municipal Health Commission(BMHC-2021-6,BJRITO-RDP-2024)Beijing Municipal Public Welfare Devel-opment and Reform Pilot Project for Medical Research Institutes(JYY2023-11,JYY2023-8).
文摘Effective treatment of intervertebral disc degeneration with biomaterials remains a challenge,owing to the difficulty in simultaneously overcoming oxidative stress and its associated cascades in the nucleus pulposus microenvironment,which includes cellular senescence,apoptosis,inflammation,and extracellular matrix(ECM)degradation.To address these issues,a multifunctional hydrogel(HG-QNT)loaded with transforming growth factorβ1(TGFβ1)and quercetin-based nanoparticles(QUNPs)is developed through borate ester bonding and Schiffbase reaction-induced crosslinking.Specifically,QUNPs fabricated via coordination and hydrophobic interactions endow the hydrogel with extraordinary antioxidative properties.Benefiting from the multi-dynamic crosslinking,the hydrogel achieves self-healing,mechanical stability,and pH-responsive release of QUNPs and TGFβ1.The HG-QNT hydrogel is demonstrated to enhance the proliferation of encapsulated nucleus pulposus cells,thereby providing an ideal platform for cell transplantation.The cooperative antioxidation of QUNPs and the hydrogel carrier renders HG-QNT effective in mitigating oxidative stress,resulting in the suppression of cellular senescence,mitochondrial dysfunction,apoptosis,excessive inflammation,and abnormal catabolism.Afterwards,TGFβ1 and QUNPs act in synergy with the hydrogel to restore the anabolic/catabolic balance by enhancing ECM synthesis.Overall,the strategy orchestrating multiple modulation by HG-QNT hydrogel shows great potential for application in intervertebral disc regeneration.
