Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings.Thus,multiple hemostatic strategies are critical for treating large bleeding wounds.In this study...Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings.Thus,multiple hemostatic strategies are critical for treating large bleeding wounds.In this study,inspired by bombardier beetles to eject toxic spray for defense,a shape-memory aerogel with an aligned microchannel structure was proposed,employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation.Bioinspired aerogels,after contact with blood,can rapidly expand inside the wound,offering robust physical barrier blocking,sealing the bleeding wound,and generating a spontaneous local chemical reaction causing an explosivelike generation of CO_(2) microbubbles,which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion.The ejection behavior,drug release kinetics,and permeation capacity were evaluated using a theoretical model and experimentally demonstrated.This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility,displaying great potential for clinical application in humans.展开更多
Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased...Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased mortality.Inspired by the attack action of torpedoes,we synthesized microcluster(MC)colloidosomes equipped with magnetic-mediated navigation and“blast”systems to deliver hemostats into the cavity of vase-type wounds.CaCO_(3)/Fe_(2)O_(3)(CF)microparticles functionalized with Arg-Gly-Asp(RGD)modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots(CDs)to form MC colloidosomes,which were loaded with thrombin and protonated tranexamic acid(TXA-NH_(3)^(+)).The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH_(3)^(+).The CO_(2) bubbles generated during disassembly produced a“blast”that propelled thrombin into the wound cavity.Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within~60 s.Furthermore,in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes.This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis,creating a new paradigm for combating trauma treatment.展开更多
Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dress...Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dressing based on a non-woven substrate,konjac glucomannan(KGM)aerogel,and bi-functional microporous starch(BMS).The KGM aerogel intercalates into the non-woven network structure,forming a hydrophilic frame to stimulate the plasma permeation toward the interior in synergy with the hydrophilic pores of the BMS.The BMS surface forms a hydrophobic matrix that fills the spaces of the KGM hydrophilic frame,contributing to the isolation and aggregation of blood cells on the surface of the HPS dressing to establish rapid hemostasis.Animal model experiments suggest reliable HPS dressing hemostatic capacity,as it is able to stop ear artery and liver bleeding within 97.6±15.2 s and 67.8±5.4 s,respectively.Furthermore,the dressings exhibit antibacterial properties and enabled wound healing within 2 weeks.In vitro hemolysis and cytotoxicity tests also confirm the biocompatibility of HPS dressings.This novel“two-in-one”hemostatic dressing facilitates tissue repair of bleeding wounds over the entire recovery period,thereby providing a convenient strategy for wound management.展开更多
The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life ...The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.展开更多
Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic st...Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic strategy based on magnetic field-mediated guidance.The biphasic Janus magnetic particle(MSS@Fe2O3-T)comprised aggregates ofα-Fe2O3 nanoparticles(Fe_(2)O_(3) NPs)as the motion actuator,negatively modified microporous starch(MSS)as the base hemostatic substrate,and thrombin as the loaded hemostatic drug.Before application,the particles were first wrapped using NaHCO_(3) and then doped with protonated tranexamic acid(TXA-NH_(3)^(+)),which ensured their high self-dispersibility in liquids.During application,the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance.In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds(“V”-shaped femoral artery and“J”-shaped liver bleeding models).The present strategy,for the first time,extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.展开更多
基金the China Agricultural Research System(No.CARS-18-ZJ0102)the Innovation Research 2035 Pilot Plan of Southwest University(SWU-XDPY22010)+1 种基金the National Natural Science Foundation of China(No.81703424)the Innovation Project for Graduate Students of Chongqing(CYB21121).
文摘Efficient hemostasis during emergency trauma with massive bleeding remains a critical challenge in prehospital settings.Thus,multiple hemostatic strategies are critical for treating large bleeding wounds.In this study,inspired by bombardier beetles to eject toxic spray for defense,a shape-memory aerogel with an aligned microchannel structure was proposed,employing thrombin-carrying microparticles loaded as a built-in engine to generate pulse ejections for enhanced drug permeation.Bioinspired aerogels,after contact with blood,can rapidly expand inside the wound,offering robust physical barrier blocking,sealing the bleeding wound,and generating a spontaneous local chemical reaction causing an explosivelike generation of CO_(2) microbubbles,which provide propulsion thrust to accelerate burst ejection from arrays of microchannels for deeper and faster drug diffusion.The ejection behavior,drug release kinetics,and permeation capacity were evaluated using a theoretical model and experimentally demonstrated.This novel aerogel showed remarkable hemostatic performance in severely bleeding wounds in a swine model and demonstrated good degradability and biocompatibility,displaying great potential for clinical application in humans.
基金supported by the China Agriculture Research System(No.CARS-18-ZJ0102)National Natural Science Foundation of China(Nos.52103096,51803170,51803171,and 81703424)+1 种基金Natural Science Foundation of Chongqing,China(grant number cstc2020jcyj-msxmX0383)Fundamental Research Funds for the Central Universities(2020CDJQY-A041).
文摘Complex yet lethal wounds with uncontrollable bleeding hinder conventional hemostats from clotting blood at the source or deep sites of injury vasculature,thereby causing massive blood loss and significantly increased mortality.Inspired by the attack action of torpedoes,we synthesized microcluster(MC)colloidosomes equipped with magnetic-mediated navigation and“blast”systems to deliver hemostats into the cavity of vase-type wounds.CaCO_(3)/Fe_(2)O_(3)(CF)microparticles functionalized with Arg-Gly-Asp(RGD)modified polyelectrolyte multilayers were co-assembled with oppositely charged zwitterionic carbon dots(CDs)to form MC colloidosomes,which were loaded with thrombin and protonated tranexamic acid(TXA-NH_(3)^(+)).The composite microparticles moved against blood flow under magnetic mediation and simultaneously disassembled for the burst release of thrombin stimulated by TXA-NH_(3)^(+).The CO_(2) bubbles generated during disassembly produced a“blast”that propelled thrombin into the wound cavity.Severe bleeding in a vase-type hemorrhage model in the rabbit liver was rapidly controlled within~60 s.Furthermore,in vivo subcutaneous muscle and liver implantation models demonstrated excellent biodegradability of MC colloidosomes.This study is the first to propose a novel strategy based on the principle of torpedoes for transporting hemostats into vase-type wounds to achieve rapid hemostasis,creating a new paradigm for combating trauma treatment.
基金National Natural Science Foundation of China(No.52103096)Natural Science Foundation of Chongqing,China(Nos.cstb2022nscq-msx0555 and cstc2020jcyj-msxmX0024)Fundamental Research Funds for Central Universities(Nos.SWU-XDPY22010,XDJK2019AC003,and XDJK2020B017).
文摘Achieving efficient hemostasis and wound management is vital to preserve life and restore health in case of extensive hemor-rhagic skin damage.Here,we develop a filter pump-like hierarchical porous-structure(HPS)dressing based on a non-woven substrate,konjac glucomannan(KGM)aerogel,and bi-functional microporous starch(BMS).The KGM aerogel intercalates into the non-woven network structure,forming a hydrophilic frame to stimulate the plasma permeation toward the interior in synergy with the hydrophilic pores of the BMS.The BMS surface forms a hydrophobic matrix that fills the spaces of the KGM hydrophilic frame,contributing to the isolation and aggregation of blood cells on the surface of the HPS dressing to establish rapid hemostasis.Animal model experiments suggest reliable HPS dressing hemostatic capacity,as it is able to stop ear artery and liver bleeding within 97.6±15.2 s and 67.8±5.4 s,respectively.Furthermore,the dressings exhibit antibacterial properties and enabled wound healing within 2 weeks.In vitro hemolysis and cytotoxicity tests also confirm the biocompatibility of HPS dressings.This novel“two-in-one”hemostatic dressing facilitates tissue repair of bleeding wounds over the entire recovery period,thereby providing a convenient strategy for wound management.
基金This work was supported by the National Natural Science Foundation of China(Nos.51803170,51803171 and 81703424)China Agricultural Research System(No.CARS-18-ZJ0102)Fundamental Research Funds for the Central Universities(2020CDJQY-A041).
文摘The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics.Bacterial infections are detrimental to our life and health.To reduce the abuse of antibiotics and treat biofilm-related bacterial infections,a biomimetic nano-antibacterial system,RBCM-NW-G namely,that controls the release of antibiotics through near infrared was prepared.The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading,and then,biomimetics are applied with red blood cell membranes(RBCM).RBCM-NW-G,which retains the performance of RBCM,shows enhanced permeability and retention effects.Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection.In addition,the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility.Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect,silver iron,and antibiotics.Finally,by constructing a mouse infection model,the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.
基金This work was supported by the National Natural Science Foundation of China(No.51703185,51803170,and 51803171)the Fundamental Research Funds for the Central Universities(nos.XDJK2019AC003 and XDJK2020B017).
文摘Severe bleeding in perforating and inflected wounds with forky cavities or fine voids encountered during prehospital treatments and surgical procedures is a complex challenge.Therefore,we present a novel hemostatic strategy based on magnetic field-mediated guidance.The biphasic Janus magnetic particle(MSS@Fe2O3-T)comprised aggregates ofα-Fe2O3 nanoparticles(Fe_(2)O_(3) NPs)as the motion actuator,negatively modified microporous starch(MSS)as the base hemostatic substrate,and thrombin as the loaded hemostatic drug.Before application,the particles were first wrapped using NaHCO_(3) and then doped with protonated tranexamic acid(TXA-NH_(3)^(+)),which ensured their high self-dispersibility in liquids.During application,the particles promptly self-diffused in blood by bubble propulsion and travelled to deep bleeding sites against reverse rushing blood flow under magnetic guidance.In vivo tests confirmed the superior hemostatic performance of the particles in perforating and inflected wounds(“V”-shaped femoral artery and“J”-shaped liver bleeding models).The present strategy,for the first time,extends the range of magnetically guided drug carriers to address the challenges in the hemorrhage control of perforating and inflected wounds.