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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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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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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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Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

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Journal of Genetics and Genomics 2024年第2期51卷 222-229页

作者： Wenbin Huang Shiying Zhang Jiuxiang Lin Yi Ding Nan Jiang Jieni Zhang Huaxiang Zhao Feng Chen Department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China key laboratory of Shaanxi province for craniofacial precision medicine research College of StomatologyXi’an Jiaotong UniversityXi’anShaanxi710004China Guangdong Provincial High-level Clinical key Specialty Guangdong Province Engineering Research Center of Oral Disease Diagnosis and TreatmentDepartment of OrthodonticsStomatological CenterPeking University Shenzhen HospitalShenzhen Peking University-The Hong Kong University of Science and Technology Medical CenterShenzhenGuangdong 518036China Department of Physiology and Pathophysiology School of Basic Medical SciencesXi'an Jiaotong UniversityXi'anShaanxi710049China National Center for Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory for Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing100101China Central laboratory Peking University School and Hospital of StomatologyBeijing100081China

Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.

关键词： Or ofacial clefts FLNB Loss-of-function mutati on Cleft palate Filamin B Actin flannent Knockout mouse

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Ptip safeguards the epigenetic control of skeletal stem cell quiescence and potency in skeletogenesis

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Science Bulletin 2024年第13期69卷 2099-2113页

作者： Jianfei Liang Jing Wang Bingdong Sui Yibo Tong Jihua Chai Qin Zhou Chenxi Zheng Hao Wang Liang Kong Haojian Zhang Yi Bai State key laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyTaikang Center for Life and Medical SciencesWuhan UniversityWuhan 430079China key laboratory of Shaanxi province for craniofacial precision medicine research College of StomatologyXi’an Jiaotong UniversityXi’an 710004China Department of Implant Dentistry College of StomatologyXi’an Jiaotong UniversityXi’an 710004China State key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China State key laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Key Laboratory of StomatologyDepartment of Oral and Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430079China Frontier Science Center for Immunology and Metabolism Medical Research InstituteWuhan UniversityWuhan 430079China Taikang Center for Life and Medical Sciences Wuhan UniversityWuhan 430079China

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency;this process requires fine-tuning regulatory *** this study,we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells(SSCs)in skeletogenesis governed by a key regulator,Ptip(also known as Paxip1,Pax interaction with transcription-activation domain protein-1).Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs,and loss of Ptip in type II collagen(Col2)^(+)progenitors causes abnormal activation and differentiation of SSCs,impaired growth plate morphogenesis,and long bone *** also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1(Pgk1)by repressing histone H3 lysine 27 acetylation(H3K27ac)at the promoter ***,inhibition of glycolysis improved the function of SSCs despite Ptip *** the best of our knowledge,this is the first study to establish an epigenetic framework based on Ptip,which safeguards skeletal stem cell quiescence and potency through metabolic *** framework is expected to improve SSC-based treatments of bone developmental disorders.

关键词： Skeletal stem cells Bone development Epigenetics Ptip Glycolysis

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Autophagy and circadian rhythms:interactions and clinical implications

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BIOCELL 2024年第1期48卷 33-45页

作者： TIANKAI DI ZHIFEI ZHOU FEN LIU YUJIANG CHEN LULU WANG State key laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China Department of Stomatology The 969th HospitalJoint Logistics Support Force of the Chinese People’s Liberation ArmyHohhot010000China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China key laboratory of Shaanxi province for craniofacial precision medicine research Clinical Research Center of Shaanxi Province for Dental and Maxillofacial DiseasesDepartment of Pediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’an710000China Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’an710032China

Autophagy is a widespread biological process that controls cellular growth,survival,development,and *** rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and *** of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian *** has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal *** can modulate circadian rhythms by breaking down proteins that regulate the circadian *** potential regulatory connection between the two has been a popular subject of clinical and fundamental *** the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the *** present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.

关键词： Autophagy Circadian rhythms Mechanism Application

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氨基酸基防污可注射自融合水凝胶的制备及其在术后防粘连中的应用

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Science China Materials 2024年第5期67卷 1521-1532页

作者：李萌张梦园刘正谢瑞琳杨宇轩申锴翔杨爱民成一龙 Engineering research Center of Energy Storage Materials and Devices Ministry of EducationSchool of ChemistryXi’an Jiaotong UniversityXi’an710049China key laboratory of Shaanxi province for craniofacial precision medicine research College of StomatologyXi’an Jiaotong UniversityXi’an710049China Department of Nuclear medicine the First Affiliated Hospital of ChinaXi’an Jiaotong UniversityXi’an710049China

设计和制备具有优异防污能力的可注射防粘连材料对预防手术后组织和器官的粘连具有重要的意义.在此,我们将含有羟基的氨基酸衍生物引入水凝胶的制备中,通过N-丙烯酰丝氨酸(ASer)的自由基聚合制备了一种新型的氢键交联水凝胶(PASer).结... 详细信息

设计和制备具有优异防污能力的可注射防粘连材料对预防手术后组织和器官的粘连具有重要的意义.在此,我们将含有羟基的氨基酸衍生物引入水凝胶的制备中,通过N-丙烯酰丝氨酸(ASer)的自由基聚合制备了一种新型的氢键交联水凝胶(PASer).结果发现一个甲基取代基的存在会对分子间氢键相互作用产生明显的影响:与聚(N-丙烯酰苏氨酸)(PAThr)水凝胶相比,PASer水凝胶具有较低的成胶浓度和增强的力学性能.值得一提的是,亲水性羟基使PASer水凝胶能够有效抵抗蛋白质吸附和细胞粘附.PASer水凝胶具有优异的力学性能、可注射性、自融合性、良好的生物相容性和适宜的体内停留时间,符合临床对术后抗粘连材料的要求.体内研究实验结果表明,PASer水凝胶在建立的小鼠腹壁缺损模型中可以有效预防术后腹膜粘连发生.

关键词： hydrogel injectability antifouling amino acid abdominal adhesion

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Expert consensus on pediatric orthodontic therapies of malocclusions in children

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International Journal of Oral Science 2024年第2期16卷 186-196页

作者： Chenchen Zhou Peipei Duan Hong He Jinlin Song Min Hu Yuehua Liu Yan Liu Jie Guo Fang Jin Yang Cao Lingyong Jiang Qingsong Ye Min Zhu Beizhan Jiang Wenhua Ruan Xiao Yuan Huang Li Rui Zou Yulou Tian Li Gao Rui Shu Jianwei Chen Renkai Liu Shujuan Zou Xiaobing Li State key laboratory of Oral Diseases&National Center for Stomatology&National Clinical research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State key laboratory of Oral Diseases&National Center for Stomatology&National Clinical research Center for Oral Diseases&Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina State key laboratory of Oral and Maxillofacial Reconstruction and Regeneration&key laboratory of Oral Biomedicine Ministry of Education&Hubei key laboratory of Stomatology&Department of Orthodontics&Center for Dentofacial Development and Sleep medicine School and Hospital of StomatologyWuhan UniversityWuhanChina Chongqing key laboratory of Oral Diseases and Biomedical Sciences&Chongqing Municipal key laboratory of Oral Biomedical Engineering of Higher Education Stomatological Hospital of Chongqing Medical UniversityChongqing Medical University&College of StomatologyChongqing Medical UniversityChongqingChina Department of Orthodontics Hospital of StomatologyJilin UniversityChangchunChina Department of Orthodontic&Oral Biomedical Engineering laboratory Shanghai Stomatological HospitalFudan UniversityShanghaiChina Department of Orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Department of Orthodontics School and Hospital of StomatologyCollege of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Laboratory for Dental Materials and Oral Tissue

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in *** its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these *** intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the *** orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition *** an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social *** consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early *** elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

关键词： permanent stated children

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Ptip维持骨骼干细胞静息态及潜能影响骨形成的表观机制（英文）

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Science Bulletin 2024年第13期 2099-2113页

作者：梁建飞王菁隋秉东童弈博柴纪华周秦郑晨曦王浩孔亮张好建白轶 State key laboratory of Oral & Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of Education Hubei Key Laboratory of Stomatology School & Hospital of Stomatology Taikang Center for Life and Medical Sciences Wuhan University key laboratory of Shaanxi province for craniofacial precision medicine research College of Stomatology Xi'an Jiaotong University Department of Implant Dentistry College of Stomatology Xi'an Jiaotong University State key laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of StomatologyShaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University State key laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences State key laboratory of Oral & Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral Diseases Shaanxi Key Laboratory of Stomatology Department of Oral and Maxillofacial Surgery School of Stomatology The Fourth Military Medical University Department of Hematology Zhongnan Hospital Wuhan University Frontier Science Center for Immunology and Metabolism Medical Research Institute Wuhan University Taikang Center for Life and Medical Sciences Wuhan University

Stem cells remain in a quiescent state for long-term maintenance and preservation of potency; this process requires fine-tuning regulatory mechanisms. In this study, we identified the epigenetic landscape along the developmental trajectory of skeletal stem cells（SSCs） in skeletogenesis governed by a key regulator, Ptip（also known as Paxip1, Pax interaction with transcription-activation domain protein-1）. Our results showed that Ptip is required for maintaining the quiescence and potency of SSCs, and loss of Ptip in type II collagen（Col2）+progenitors causes abnormal activation and differentiation of SSCs, impaired growth plate morphogenesis, and long bone dysplasia. We also found that Ptip suppressed the glycolysis of SSCs through downregulation of phosphoglycerate kinase 1（Pgk1） by repressing histone H3 lysine 27acetylation（H3K27ac） at the promoter region. Notably, inhibition of glycolysis improved the function of SSCs despite Ptip deficiency. To the best of our knowledge, this is the first study to establish an epigenetic framework based on Ptip, which safeguards skeletal stem cell quiescence and potency through metabolic control. This framework is expected to improve SSC-based treatments of bone developmental disorders.

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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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