The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response ...The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism.In this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment.Particularly,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional performance.The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres.In addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA.In summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA.展开更多
Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants.Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported,the harsh and tedi...Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants.Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported,the harsh and tedious synthesis greatly compromises their application,and more importantly,the bacterial resistance property has seldom been investigated in combination with the lubrication property.In this study,bioinspired by the performances of mussel and articular cartilage,we successfully synthesized self-adhesive lubricated coating and simultaneously achieved optimal lubrication and bacterial resistance properties.Additionally,we reported the mechanism of bacterial resistance on the nanoscale by studying the adhesion interactions between biomimetic coating and hydrophilic/hydrophobic tip or living bacteria via atomic force microscopy.In summary,the self-adhesive lubricated coating can effectively enhance lubrication and bacterial resistance performances based on hydration lubrication and hydration repulsion,and represent a universal and facial strategy for surface functionalization of biomedical implants.展开更多
Accurate drug delivery to the lesion has been deliberated for several decades,but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine.Although injecti...Accurate drug delivery to the lesion has been deliberated for several decades,but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine.Although injection would reduce first-pass effect,macrophages in the blood can still recognize and phagocytose nanomedicine.Here we show that a lubricated nanocontainer,which is prepared based on polyelectrolytes and mesoporous silica nanoparticles,can accurately target muscarinic bioreceptor while escaping from the identification of macrophages.Through in vitro and in vivo studies,this nanocontainer,combining both immune escape and bioreceptor targeting,has greatly improved the drug bioavailability.Additionally,this nanocontainer shows good biocompatibility,and the targeted heart tissues and other important metabolic organs,such as liver and kidney,keep physiological structures and functions without the detection of side effects.Furthermore,the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation.We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery,which can provide a fundamental approach for the design of related biomaterials.展开更多
基金This study was financially supported by National Natural Science Foundation of China(52022043 and 81930051)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(20191080593)+3 种基金Precision Medicine Foundation,Tsinghua University,China(10001020107)Shanghai Jiao Tong University“Medical and Research”Program(ZH2018ZDA04)Science and Technology Commission of Shanghai Municipality(18ZR1434200,18140901500 and 19440760400)Research Fund of State Key Laboratory of Tribology,Tsinghua University,China(SKLT2020C11).
文摘The occurrence of osteoarthritis(OA)is highly associated with the reduced lubrication property of the joint,where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism.In this study,bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel,we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment.Particularly,the lubricating microspheres(GelMA@DMA-MPC)were fabricated by dip coating a self-adhesive polymer(DMA-MPC,synthesized by free radical copolymerization)on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres(GelMA,prepared via microfluidic technology),and encapsulated with an anti-inflammatory drug of diclofenac sodium(DS)to achieve the dual-functional performance.The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres.In addition,the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model,and the biological tests including qRT-PCR,immunofluorescence staining assay,X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA.In summary,the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release,therefore representing a facile and promising technique for the treatment of OA.
基金supported by National Natural Science Foundation of China(52022043)Tsinghua University Initiative Scientific Research Program(20197050026)+2 种基金Precision Medicine Foundation,Tsinghua University,China(10001020120)Capital’s Funds for Health Improvement and Research(2020-2Z-40810)Research Fund of State Key Laboratory of Tribology,Tsinghua University,China(SKLT2020C11).
文摘Limited surface lubrication and bacterial biofilm formation pose great challenges to biomedical implants.Although hydrophilic lubricated coatings and bacterial resistance coatings have been reported,the harsh and tedious synthesis greatly compromises their application,and more importantly,the bacterial resistance property has seldom been investigated in combination with the lubrication property.In this study,bioinspired by the performances of mussel and articular cartilage,we successfully synthesized self-adhesive lubricated coating and simultaneously achieved optimal lubrication and bacterial resistance properties.Additionally,we reported the mechanism of bacterial resistance on the nanoscale by studying the adhesion interactions between biomimetic coating and hydrophilic/hydrophobic tip or living bacteria via atomic force microscopy.In summary,the self-adhesive lubricated coating can effectively enhance lubrication and bacterial resistance performances based on hydration lubrication and hydration repulsion,and represent a universal and facial strategy for surface functionalization of biomedical implants.
基金supported by National Natural Science Foundation of China(52022043)Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program(20191080593)+3 种基金Capital’s Funds for Health Improvement and Research(2020-2Z-40810)Precision Medicine Foundation,Tsinghua University,China(10001020107 and 10001020120)Shanghai Collaborative Innovation Center for Translational Medicine(TM201802)Science and Technology Commission of Shanghai Municipality Grant(17140902500).
文摘Accurate drug delivery to the lesion has been deliberated for several decades,but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine.Although injection would reduce first-pass effect,macrophages in the blood can still recognize and phagocytose nanomedicine.Here we show that a lubricated nanocontainer,which is prepared based on polyelectrolytes and mesoporous silica nanoparticles,can accurately target muscarinic bioreceptor while escaping from the identification of macrophages.Through in vitro and in vivo studies,this nanocontainer,combining both immune escape and bioreceptor targeting,has greatly improved the drug bioavailability.Additionally,this nanocontainer shows good biocompatibility,and the targeted heart tissues and other important metabolic organs,such as liver and kidney,keep physiological structures and functions without the detection of side effects.Furthermore,the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation.We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery,which can provide a fundamental approach for the design of related biomaterials.