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Bioinspired Hemostatic Strategy via Pulse Ejections for Severe Bleeding Wounds

research 2024年第1期2023卷 281-299页

作者： Bitao Lu Enling Hu Weiwei Ding Wenyi Wang Ruiqi Xie Kun Yu Fei Lu Guangqian Lan Fangyin Dai State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile Chongqing 400715China Division of Trauma and Surgical Intensive Care Unit Research Institute of General SurgeryJinling HospitalMedical School of Nanjing UniversityNanjing210002 Jiangsu ProvinceChina Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHong KongChina

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.

关键词： wound sealing offering

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Microcluster colloidosomes for hemostat delivery into complex wounds:A platform inspired by the attack action of torpedoes

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Bioactive Materials 2022年第10期7卷 372-387页

作者： Bitao Lu Enling Hu Ruiqi Xie Kun Yu Fei Lu Rong Bao Chenhui Wang Guangqian Lan Fangyin Dai State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing400715China Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile Chongqing400715China The Ninth People’s Hospital of chongqing No.69 Jialing Village BeiBei DistrictChongqing400715China chongqing Key Laboratory of Natural Product Synthesis and Drug research School of Pharmaceutical SciencesChongqing University55 South Daxuecheng RoadChongqing401331China

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.

关键词： Torpedoes-inspired Microcluster colloidosomes Magnetic guidance Disintegration Hemostasis

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Dual-Driven Hemostats Featured with Puncturing Erythrocytes for Severe Bleeding in Complex Wounds

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research 2022年第4期2022卷 119-135页

作者： Haoyu Qiu Guangqian Lan Weiwei Ding Xinyu Wang Wenyi Wang Dahua Shou Fei Lu Enling Hu Kun Yu Songmin Shang Ruiqi Xie State Key Laboratory of ilkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile Chongqing 400715China Division of Trauma and Surgical Intensive Care Unit Research Institute of General SurgeryJinling HospitalMedical School of Nanjing UniversityNanjing210002 Jiangsu ProvinceChina Institute of textiles and Clothing The Hong Kong Polytechnic UniversityKowloonHong Kong

Achieving rapid hemostasis in complex and deep wounds with secluded hemorrhagic sites is still a challenge because of the difficulty in delivering hemostats to these sites.In this study,a Janus particle,SEC-Fe@CaT with dual-driven forces,bubble-driving,and magnetic field–(MF–)mediated driving,was prepared via in situ loading of Fe_(3)O_(4) on a sunflower sporopollenin exine capsule(SEC),and followed by growth of flower-shaped CaCO3 clusters.The bubble-driving forces enabled SEC-Fe@CaT to self-diffuse in the blood to eliminate agglomeration,and the MF-mediated driving force facilitated the SEC-Fe@CaT countercurrent against blood to access deep bleeding sites in the wounds.During the movement in blood flow,the meteor hammer-like SEC from SEC-Fe@CaT can puncture red blood cells(RBCs)to release procoagulants,thus promoting activation of platelet and rapid hemostasis.Animal tests suggested that SEC-Fe@CaT stopped bleeding in as short as 30 and 45 s in femoral artery and liver hemorrhage models,respectively.In contrast,the similar commercial product Celox™required approximately 70 s to stop the bleeding in both bleeding modes.This study demonstrates a new hemostat platform for rapid hemostasis in deep and complex wounds.It was the first attempt integrating geometric structure of sunflower pollen with dual-driven movement in hemostasis.

关键词： driving bubble eliminate

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Magnetic field-mediated Janus particles with sustained driving capability for severe bleeding control in perforating and inflected wounds

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Bioactive Materials 2021年第12期6卷 4625-4639页

作者： Qing Li Enling Hu Kun Yu Mengxing Lu Ruiqi Xie Fei Lu Bitao Lu Rong Bao Guangqian Lan State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing400715China Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile Chongqing400715China The Ninth People’s Hospital of chongqing No.69 Jialing VillageBeiBei DistrictChongqing400715China

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.

关键词： Janus particle Sustained driving Magnetic guidance Hemostasis Complex wound

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Erythrocyte membrane-camouflaged nanoworms with on-demand antibiotic release for eradicating biofilms using near-infrared irradiation

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Bioactive Materials 2021年第9期6卷 2956-2968页

作者： Luoxiao Ran Bitao Lu Haoyu Qiu Guofang Zhou Jing Jiang Enling Hu Fangyin Dai Guangqian Lan State Key Laboratory of Silkworm Genome Biology College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing400715China Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile Chongqing400715China chongqing General Hospital University of Chinese Academy of Sciences No.118Xingguang AvenueLiangjiang New AreaChongqingChina

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.

关键词： Red blood cell membrane Nanoworms Antibiotics release Bacterial infection

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In situ assembly of Ag nanoparticles（AgNPs） on porous silkworm cocoon-based would film:enhanced antimicrobial and wound healing activity

In situ assembly of Ag nanoparticles（AgNPs） on porous silk...

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中国蚕学会第九届青年学术研讨会

作者： Kun Yu Fei Lu Qing Li Honglei Chen Bitao Lu Jiawei Liu Zhiquan Li Fangying Dai Dayang Wu Guangqian Lan College of textile and Garments Southwest University Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile The Ninth People’s Hospital of chongqing

Preventing wound infection and retaining an appropriate level of moisture around wounds represent the most critical issues in wound treatment.Towards these ends,special focus has been placed on Bombyx mori cocoons because the protective function of the silkworm cocoon resembles the manner in which the skin protects the human body.We have designed a facile technique to develop a novel silkworm cocoon-based wound film（SCWF） wound dressing utilizing a CaCl2-ethanol-H2 O solution.To improve the anti-bacterial performance of SCWF,we have incorporated the ability of silk sericin to act as a reducing agent for the conversion of Ag+ to Ag,yielding nanoparticles（AgNPs） linked together by peptide bonds of silkworm cocoon wound film（SCWF-AgNPs）.SCWF-AgNP dressing exhibited excellent biocompatibility,anti-bacterial performance,and good extensibility.Furthermore,in vivo experiments indicated that SCWF-AgNP dressing was able to significantly accelerate the healing rate of infected wounds in New Zealand White rabbits and histological examination revealed that it aided in the successful reconstruction of intact and thickened epidermis during 14 days of healing of impaired wound tissue.These results demonstrate that the present approach might shed new light on the design of anti-bacterial materials such as SCWF-AgNPs with promising applications in wound dressing.

关键词： Silkworm cocoon Silver nanoparticles Infected wound healing Silk fibroin Antibacterial performance

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Artemisinin is highly soluble in polyethylene Glycol 4000 and such solution has multiple biological effects

Artemisinin is highly soluble in polyethylene Glycol 4000 an...

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中国蚕学会2021年学术年会

作者： Yu Bao Zhi Li Si-Hao Chen Li-Zhi Gao Zu-Lan Liu Lan Cheng Yan Peng Xiao-Ling Tong Fang-Yin Dai State Key Laboratory of Silkworm Genome Biology Southwest University Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile College of Textile and GarmentSouthwest University Key Laboratory of Sericultural Biology and Genetic Breeding Ministry of AgricultureCollege of BiotechnologySouthwest University

Artemisinin has a significant role in treatment of malaria,as well as effective anti-inflammatory and anti-cancer activities.However,such problems as poor water solubility and easy recrystallization limit its application.In this study,polyethylene glycol,a solvent which is widely used in pharmaceutics,was introduced to prepare an artemisinin dissolution.Under the action of hydrogen bonding in 12% polyethylene glycol 4000 solvent,the maximum solubility of artemisinin could reach up to 1 mg/m L.Meanwhile,biological functions of such artemisinin solution were evaluated.The obtained artemisinin solution had a significant inhibitory effect on Gram-positive bacteria,Gram-negative bacteria and fungi.As for the anti-inflammatory property,0.031 mg/mL artemisinin solution had an obvious inhibitory effect on nitric oxide release in inflammatory cells,and the survival rate of cells was greater than 50%.Low concentration of the obtained artemisinin solution（0.031 mg/mL） had no significant cytotoxicity,while it displayed selective inhibition in cancer cells.IC50 for human hepatoma cells BEL-7404,SMMC7721 and Hep G2 is 0.0016 mg/mL,0.0084 mg/mL and 0.0541 mg/mL,respectively.In conclusion,the 12% PEG4000-assisted artemisinin solution has a good biological effect and it can be further applied in pharmaceutics,biomaterials and medicine.

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Characterization of silkworm larvae growth and properties of silk fibres after direct feeding of copper or silver anoparticles

Characterization of silkworm larvae growth and properties of...

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中国蚕学会第九届青年学术研讨会

作者： Lan Cheng Huiming Huang Shaoyong Chen Wenlu Wang Fangyin Dai Hongping Zhao Chongqing Engineering Research Center of Biomaterial Fiber and Modern Textile College of Textile and GarmentSouthwest University Institute of Biomechanics and Medical engineering Tsinghua University State Key Laboratory of Silkworm Genome Biology Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural MinistryCollege of BiotechnologySouthwest University

In this study,we raised silkworm larvae from the fifth instar with a modified diet of copper or silver nanoparticles（NPs） combined with mulberry leaves.Silkworm larvae growth was characterized according to larvae weight,survival rate,cocooning and silk glands microstructures.Cu or Ag element distributions in their tissues were examined with inductively couple plasma mass spectroscopy.The properties of silkworm silks were investigated with Fourier transform infrared（FTIR） and amino acid analyses,thermogravimetric and quasi-static tensile tests.Our results depicted a primary concentration distribution map of Cu or Ag element in silkworm larva tissues by the modified diet,and Cu or Ag NPs had slightly negative influences on the growth of the silkworm larvae.Results from FTIR spectra and amino acid analyses showed that the Cu or Ag NPs slightly inhibited the β-sheet conformation transition and promoted the crystallization of silk protein.Furthermore,copper or silver NPs obviously enhanced the thermal stability and mechanical properties of silkworm silk with a coupling competitive mechanism.This study expands our ability to obtain distinctive reinforced silkworm silks in a green and effective way and to gain an elementary comprehension of nano-bio interactions between a model organism,Bombyx mori silkworm,and metallic nanoparticles.

关键词： Bombyx mori silkworm metallic nanoparticles silk gland silk fibre metallic element distribution mechanical property

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