Inflammatory responses triggered by foreign body rejection or detached wear particles are major contributors to the failure of titanium(Ti)-based orthopedic implants.One of the most common complications is aseptic loo...Inflammatory responses triggered by foreign body rejection or detached wear particles are major contributors to the failure of titanium(Ti)-based orthopedic implants.One of the most common complications is aseptic loos-ening.To address this challenge,a nanorod-arrayed hydroxyapatite(HA)coating co-doped with multiple ions(Sr^(2+),Mg^(2+),Zn^(2+),CO_(3)^(2-),and SiO_(4)^(4-))was developed,to mimic the bone matrix and enhance immunoosteogenesis.The coating exhibits strong adhesion strength and long-term interfacial stability.Ion-induced lat-tice distortion accelerates HA degradation,promoting the doped-ion release.These bioactive ions drive macrophage(MΦs)polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype,thereby enhancing vascularized osseointegration.To evaluate the risk of aseptic loosening induced by detached nano-rods,we synthesized nanorod-like particles with identical composition and morphology to those in the arrayed coating.Their effects on MΦpolarization and the underlying mechanisms were then systematically investigated.Compared to undoped particles,multi-ion doped HA nanoparticles are more easily phagocytosed and degraded within lysosomes,enabling faster ion release and thereby facilitating M1-M2 transition.Transcriptomic analysis reveals that the nanoparticle degradation-mediated ion release elevates intracellular calcium levels in MΦs,which activates antioxidant pathways and induces a metabolic shift toward fatty acid oxidation.This metabolic reprogramming subsequently activates immunoregulatory pathways,with the PPAR pathway serving as a central axis,thereby promoting M2 polarization,inhibiting osteoclastogenesis,and ultimately preventing aseptic loos-ening.Collectively,this study presents a coating design that not only promotes osseointegration but also retains anti-inflammatory potential even in the event of particle detachment,offering a promising strategy to mitigate aseptic loosening.展开更多
Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early...Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.52531009,32471383)National Key Research and Development Program of China(Grant No.2023YFC2412600)+1 种基金China Postdoctoral Science Foundation(2023M732756)Natural Science Foundation of Shaanxi Province(No.2024JC-YBQN-0454,2024PTZCK-15,2023LLQY44,2024JC-YBQN-0368),financially supporting this work.
文摘Inflammatory responses triggered by foreign body rejection or detached wear particles are major contributors to the failure of titanium(Ti)-based orthopedic implants.One of the most common complications is aseptic loos-ening.To address this challenge,a nanorod-arrayed hydroxyapatite(HA)coating co-doped with multiple ions(Sr^(2+),Mg^(2+),Zn^(2+),CO_(3)^(2-),and SiO_(4)^(4-))was developed,to mimic the bone matrix and enhance immunoosteogenesis.The coating exhibits strong adhesion strength and long-term interfacial stability.Ion-induced lat-tice distortion accelerates HA degradation,promoting the doped-ion release.These bioactive ions drive macrophage(MΦs)polarization from pro-inflammatory M1 to anti-inflammatory M2 phenotype,thereby enhancing vascularized osseointegration.To evaluate the risk of aseptic loosening induced by detached nano-rods,we synthesized nanorod-like particles with identical composition and morphology to those in the arrayed coating.Their effects on MΦpolarization and the underlying mechanisms were then systematically investigated.Compared to undoped particles,multi-ion doped HA nanoparticles are more easily phagocytosed and degraded within lysosomes,enabling faster ion release and thereby facilitating M1-M2 transition.Transcriptomic analysis reveals that the nanoparticle degradation-mediated ion release elevates intracellular calcium levels in MΦs,which activates antioxidant pathways and induces a metabolic shift toward fatty acid oxidation.This metabolic reprogramming subsequently activates immunoregulatory pathways,with the PPAR pathway serving as a central axis,thereby promoting M2 polarization,inhibiting osteoclastogenesis,and ultimately preventing aseptic loos-ening.Collectively,this study presents a coating design that not only promotes osseointegration but also retains anti-inflammatory potential even in the event of particle detachment,offering a promising strategy to mitigate aseptic loosening.
基金We would like to thank the support by the National Key Research and Development Program of China(2018YFA0703000)National Natural Science Foundation of China(Grant No.51875518)+1 种基金Key Research and Development Projects of Zhejiang Province(Grant No.2017C01054 and No.2018C03062)the Fundamental Research Funds for the Central Universities(Grant No.2019XZZX003-02,2019FZA4002).
文摘Treatments for lesions in central nervous system(CNS)are always faced with challenges due to the anatomical and physiological particularity of the CNS despite the fact that several achievements have been made in early diagnosis and precision medicine to improve the survival and quality of life of patients with brain tumors in recent years.Understanding the complexity as well as role of the microenvironment of brain tumors may suggest a better revealing of the molecular mechanism of brain tumors and new therapeutic directions,which requires an accurate recapitulation of the complex microenvironment of human brain in vitro.Here,a 3D bioprinted in vitro brain matrix-mimetic microenvironment model with hyaluronic acid(HA)and normal glial cells(HEBs)is developed which simulates both mechanical and biological properties of human brain microenvironment in vivo through the investigation of the formulation of bioinks and optimization of printing process and parameters to study the effects of different concentration of gelatin(GA)within the bioink and different printing structures of the scaffold on the performance of the brain matrix-mimetic microenvironment models.The study provides experimental models for the exploration of the multiple factors in the brain microenvironment and scaffolds for GBM invasion study.
