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ROS-responsive hydrogels with spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs for the repair of MRSA-infected wounds

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Regenerative Biomaterials 2024年第1期3卷 119-131页

作者： Bowen Qiao Jiaxin Wang Lipeng Qiao Aziz Maleki Yongping Liang baolin guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China Zanjan Pharmaceutical Nanotechnology Research Center(ZPNRC) Zanjan 45139-56184Iran Department of Orthopaedics The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061People’s Republic of China

For the treatment of MRSA-infected wounds,the spatiotemporally sequential delivery of antibacterial and anti-inflammatory drugs is a promising *** this study,ROS-responsive HA-PBA/PVA(HPA)hydrogel was prepared by phenylborate ester bond cross-linking between hyaluronic acid-grafted 3-amino phenylboronic acid(HA-PBA)and polyvinyl alcohol(PVA)to achieve spatiotemporally controlled release of two kinds of drug to treat MRSA-infected *** hydrophilic antibiotic moxifloxacin(M)was directly loaded in the *** hydrophobic curcumin(Cur)with anti-inflammatory function was first mixed with Pluronic F127(PF)to form Cur-encapsulated PF micelles(Cur-PF),and then loaded into the HPA *** to the different hydrophilic and hydrophobic nature of moxifloxacin and Cur and their different existing forms in the HPA hydrogel,the final HPA/M&Cur-PF hydrogel can achieve different spatiotemporally sequential delivery of the two *** addition,the swelling,degradation,self-healing,antibacterial,anti-inflammatory,antioxidant property,and biocompatibility of hydrogels were ***,in the MRSA-infected mouse skin wound,the hydrogel-treated group showed faster wound closure,less inflammation and more collagen *** experiments further confirmed that the hydrogel promoted better repair by reducing inflammation(TNF-a)and promoting vascular(VEGF)*** conclusion,this HPA/M&CurPF hydrogel that can spatiotemporally sequential deliver antibacterial and anti-inflammatory drugs showed great potential for the repair of MRSA-infected skin wounds.

关键词： MRSA-infected wounds spatiotemporally sequential delivery antibacterial anti-inflammatory

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Bacteria-responsive programmed self-activating antibacterial hydrogel to remodel regeneration microenvironment for infected wound healing

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National Science Review 2024年第4期11卷 254-270页

作者： Yutong Yang Jiaxin Wang Shengfei Huang Meng Li Jueying Chen Dandan Pei Zhen Tang baolin guo State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and Technology and Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine ResearchCollege of Stomatology Xi'an Jiaotong University Department of Orthopedics Tangdu Hospital Fourth Military Medical University Department of Orthopedics The First Affiliated Hospital of Xi'an Jiaotong University

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, p H-responsive H2O2self-supplying composite nanozyme（MSCO） and p H/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase（PPEL） were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan（CA） and phenylboronic acid-modified oxidized dextran（ODP） to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide（NO） release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound *** self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings.

关键词： bacterial response hydrogel dressing multiple nanozyme activity biofilm elimination infected motion wound healing

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High-strength antiswelling adhesive achieves both hemostasis and wound healing

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Journal of Pharmaceutical Analysis 2024年第6期14卷 781-784页

作者： Xin Zhao Jinlong Luo Ying Huang Lei Mu Jueying Chen Zhen Liang Zhanhai Yin Dake Chu Yong Han baolin guo State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi'an Jiaotong UniversityXi'an710049China Department of Plastic Surgery Xijing HospitalAir Force Medical UniversityXi'an710032China Department of Orthopaedics The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of Gastroenterology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi'an Jiaotong UniversityXi'an710049China

Skin is one of the most vulnerable tissues,but there is a lack of injectable bioactive hydrogel dressings,which possess high strength,antiswelling capacity,and wet tissue adhesiveness,but also a rapid gelling process to enable rapid hemostasis,sutureless wound closure,and scarless healing of infected skin wounds[1e5].A new injectable,antibacterial,and multifunctional hydrogel dressings based on poly(citric acid-co-polyethylene glycol)-g-dopamine(PCPD)and amino-terminated Pluronic F127(APF)mi-celles loaded with astragaloside IV(AS)was developed for this pur-pose,as shown in Fig.1A[6].

关键词： healing wound stasis

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Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

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Chinese Journal of Natural Medicines 2024年第5期22卷 466-480页

作者： LIANG Haizhen CHEN Xiaojuan LI Qi ZHANG Mengmeng LU Pengxin ZHANG Jie SONG Juan ZHANG Tao guo baolin MA Baiping Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China AnKang Chia Tai Pharmaceutical Co. Ltd.Shaanxi 725000China

Sixteen new dammarane-type triterpenoid saponins(1-16)featuring diverse structural variations in the side chain at C-17,along with twenty-one known analogues(17-37),have been isolated from the rhizomes of Gynostemma longipes ***,a plant renowned for its medicinal and edible *** structural elucidation of these compounds was accomplished through comprehensive analyses of 1D and 2D NMR and HRMS spectroscopic data,supplemented by comparison with previously reported *** assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells(PC12 cells)revealed that nine saponins exhibited significant anti-hypoxic *** investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that compounds 22 and 36 markedly reduced the levels of hypoxia-induced ***,these compounds were found to decrease the release of lactate dehydrogenase(LDH)and malondialdehyde(MDA),while increasing the activity of superoxide dismutase(SOD),thereby indicating that the saponins could mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative *** findings offer substantial evidence for the future utilization and development of ***,identifying dammarane-type triterpenoid saponins as its active anti-hypoxic constituents.

关键词： Gynostemma longipes Dammarane-type saponins Anti-hypoxia effect Apoptosis

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Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering

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Nano-Micro Letters 2022年第1期14卷 1-46页

作者： Rui Yu Hualei Zhang baolin guo State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049People’s Republic of China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049People’s Republic of China

Conductive biomaterials based on conductive polymers,carbon nanomaterials,or conductive inorganic nanomaterials demonstrate great potential in wound healing and skin tissue engineering,owing to the similar conductivity to human skin,good antioxidant and antibacterial activities,electrically controlled drug delivery,and photothermal ***,a review highlights the design and application of conductive biomaterials for wound healing and skin tissue engineering is *** this review,the design and fabrication methods of conductive biomaterials with various structural forms including film,nanofiber,membrane,hydrogel,sponge,foam,and acellular dermal matrix for applications in wound healing and skin tissue engineering and the corresponding mechanism in promoting the healing process were *** approaches that conductive biomaterials realize their great value in healing wounds via three main strategies(electrotherapy,wound dressing,and wound assessment)were *** application of conductive biomaterials as wound dressing when facing different wounds including acute wound and chronic wound(infected wound and diabetic wound)and for wound monitoring is discussed in *** challenges and perspectives in designing and developing multifunctional conductive biomaterials are proposed as well.

关键词： Conducting polymers Inorganic nanomaterials Biomaterials Electrotherapy Wound monitoring

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Emerging hemostatic materials for non-compressible hemorrhage control

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National Science Review 2022年第11期9卷 223-239页

作者： Ruonan Dong Hualei Zhang baolin guo State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and Technology Xi'an Jiaotong University Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of Stomatology Xi'an Jiaotong University

Non-compressible hemorrhage control is a big challenge in both civilian life and the battlefield, causing a majority of deaths among all traumatic injury mortalities. Unexpected non-compressible bleeding not only happens in pre-hospital situations but also leads to a high risk of death during surgical processes throughout in-hospital treatment. Hemostatic materials for pre-hospital treatment or surgical procedures for non-compressible hemorrhage control have drawn more and more attention in recent years and several commercialized products have been developed. However, these products have all shown non-negligible limitations and researchers are focusing on developing more effective hemostatic materials for non-compressible hemorrhage control. Different hemostatic strategies(physical, chemical and biological)have been proposed and different forms(sponges/foams, sealants/adhesives, microparticles/powders and platelet mimics) of hemostatic materials have been developed based on these strategies. A summary of the requirements, state-of-the-art studies and commercial products of non-compressible hemorrhage-control materials is provided in this review with particular attention on the advantages and limitations of their emerging forms, to give a clear understanding of the progress that has been made in this area and the promising directions for future generations.

关键词： non-compressible hemorrhage control commercialized hemorrhage-control strategies hemostatic sponge hydrogel microparticle platelet mimics

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山区高速公路钢筋混凝土高墩施工技术

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粘接 2024年第8期51卷 165-168页

作者：王冠刘刚郭保林山东高速临滕公路有限公司山东临沂273400 山东高速工程项目管理有限公司山东济南250014 山东省交通科学研究院山东济南250014 山东省混凝土材料与桥梁结构工程技术研究中心山东济南250014

临沂至滕州公路施工全长为15.97 km,其中建造特大桥两座,分别为温凉河特大桥和黑风口特大桥。针对工程的施工重难点问题提出施工方案。温凉河特大桥上半部分的结构为先简支后连续的装配式预应力(后张)T型梁;在其基础上,下半部分结构的... 详细信息

临沂至滕州公路施工全长为15.97 km,其中建造特大桥两座,分别为温凉河特大桥和黑风口特大桥。针对工程的施工重难点问题提出施工方案。温凉河特大桥上半部分的结构为先简支后连续的装配式预应力(后张)T型梁;在其基础上,下半部分结构的桥墩采用空心墩,矩形实心墩,桩基础,小桩号桥台采用U台,扩大基础;大桩号桥台采用肋板台,桩基础。黑风口特大桥上半部分结构同样为先简支后连续的装配式预应力混凝土(后张)T梁;下半部分结构的桥墩采用矩形实心墩、柱式墩,桩基础;桥台使用肋板台,桩基础,墩台布置采用径向布置。温凉河特大桥、黑风口特大桥高墩施工均采用翻模法施工。

关键词：预应力混凝土实心墩空心墩桩基础桥梁施工

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Antibacterial conductive self-healable supramolecular hydrogel dressing for infected motional wound healing

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Science China Chemistry 2022年第11期65卷 2238-2251页

作者： Rui Yu Zhenlong Li guoying Pan baolin guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi'an 710049China State Key Laboratory for Mechanical Behavior of Materials Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi'an710049China

Wounds on stretchable parts of the human body cause prolonged suffering and involve more severe healing processes than wounds on stationary parts. However, they have received insufficient attention compared with other types of chronic wounds. In this study, a novel supramolecular gelatin(GT) hydrogel composed of GT-graft-aniline tetramer and quaternized chitosan was presented. The hydrogel was crosslinked by monoaldehyde β-cyclodextrin via host-guest interaction and dynamic Schiff base and was free from permanent covalent bonds, heavy metals, and oxidants. Given its dynamic feature, the hydrogel exhibited flexibility, self-healing, and tissue adhesiveness and well adapted to motion wounds. Moreover, the hydrogel was bioactive with conductivity, antioxidant property, hemostatic effect, antibacterial, and photothermal effect(the killing ratio for methicillinresistant Staphylococcus aureus(MRSA) was higher than 99.8% after 5 min of near-infrared irradiation) and exhibited ondemand removability. In the full-thickness MRSA-infected motional wound healing experiment, this novel hydrogel exhibited a significantly enhanced wound healing efficacy with a fast wound closure ratio(about 99.0% for 14 days), mild inflammatory response, high level of collagen deposition, and enhanced re-epithelialization by downregulating interleukin-6 and CD68 and upregulating vascular endothelial growth factor. The results indicated that this hydrogel has great potential in wound healing and skin tissue engineering and serves as an inspiration for the design of supramolecular biomaterials.

关键词： supramolecular hydrogel self-healing tissue adhesion joint wound

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Porous photothermal antibacterial antioxidant dual–crosslinked cryogel based on hyaluronic acid/polydopamine for non-compressible hemostasis and infectious wound repair

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Journal of Materials Science & Technology 2022年第26期121卷 207-219页

作者： Chunbo Wang Yuqing Liang Ying Huang Meng Li baolin guo Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049China State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049China

Cryogel dressings with good absorption ability and photothermal antibacterial properties for preventing wound infections and treating infected wounds have attracted widespread *** this work,a series of cryogels with macroporous structure,antioxidant and photothermal properties were prepared based on adipic dihydrazide modified hyaluronic acid(HA-ADH),and dopamine(DA).The antioxidant properties,hemostatic properties,near infrared(NIR)assisted photothermal antibacterial ability provided by polydopamine,recyclable compression mechanical properties,and cytocompatibility were *** results demonstrated that the HA-ADH/DA cryogels have stable mechanical properties,great antibacterial properties against ***(EC)and methicillin-resistant ***(MRSA).The high swelling ratio due to the high water retention of HA equipped the cryogels with the capability of absorbing exuded blood and excessive tissue fluid in the infected full-thickness skin defect model of *** cryogels demonstrated good cytocompatibility and antioxidant performance through cell tests and 1,1-diphenyl-2-methylbenzohydrazino(DPPH)scavenging efficiency *** cryogels showed enhanced blood-clotting index(BCI)and better hemostatic ability in the mouse liver trauma model and the rat deep noncompressible liver defect model compared with gauze and gelatin ***,compared with commercial TegadermTMdressing in vivo,the HA-ADH/DA cryogels could greatly promote infected skin wound healing in a full-thickness infected skin defect wound *** summary,the macroporous HAADH/DA cryogels with good antioxidant,high swelling ratio,photothermal antibacterial property,and biocompatibility are a promising hemostatic material and wound healing dressing.

关键词： Dopamine-hyaluronic acid-based cryogels Antioxidant Photothermal antibacterial Wound healing Hemostasis

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Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing

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Nano-Micro Letters 2022年第11期14卷 256-274页

作者： Yuqing Liang Huiru Xu Zhenlong Li Aodi Zhangji baolin guo State Key Laboratory for Mechanical Behavior of Materials and Frontier Institute of Science and TechnologyXi’an Jiaotong UniversityXi’an 710049People’s Republic of China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi’an Jiaotong UniversityXi’an 710049People’s Republic of China

Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound *** by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless *** dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened ***,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during ***,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic *** in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.

关键词： Bioinspired injectable hydrogel Tissue sealant Temperature-dependent adhesion Reversible adhesion Wound healing

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