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Peri-implant gas accumulation in response to magnesium-based musculoskeletal biomaterials:Reframing current evidence for preclinical research and clinical evaluation

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Journal of Magnesium and Alloys 2024年第1期12卷 59-71页

作者： Yu Sun Heike Helmholz Regine Willumeit-Römer Institute of Metallic biomaterials Helmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany

Historically,the rapid degradation and massive gas release from magnesium(Mg)implants resulted in severe emphysema and mechanical *** the advent of new alloys and surface treatment methods,optimized Mg implants have re-entered clinics since last decade with reliable ***,the optimization aims at slowing down the degradation process,rather than exemption of the gas *** study involved a systematic evaluation of current preclinical and clinical evidence,regarding the physical signs,symptoms,radiological features,pathological findings and complications potentially associated with peri±implant gas accumulation(PIGA)after musculoskeletal Mg *** literature search identified 196 potentially relevant publications,and 51 papers were enrolled for further analysis,including 22 preclinical tests and 29 clinical studies published from 2005 to *** Mg-based materials have been evaluated in animal research,and the application of pure Mg and Mg alloys have been reported in clinical follow-ups involving multiple anatomical sites and musculoskeletal *** tissue and intraosseous PIGA are common in both animal tests and clinical follow-ups,and potentially associated with certain adverse *** examinations especially micro-CT and clinical CT scans provide valuable information for quantitative and longitudinal *** according to simulation tests involving Mg implantation and chemical processing,tissue fixation could lead to an increase in the volume of gas cavity,thus the results obtained from ex vivo imaging or histopathological evaluations should be interpreted with *** still lacks standardized procedures or consensus for both preclinical and clinical evaluation of ***,by providing focused insights into the topic,this evidence-based study will facilitate future animal tests and clinical evaluations,and support developing biocompatible Mg implants for the treatment of musculoskeletal

关键词： Magnesium implant Degradation Hydrogen Gas release Postoperative follow-up

Systemic modulation of skeletal mineralization by magnesium implant promoting fracture healing: Radiological exploration enhanced with PCA-based machine learning in a rat femoral model

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Journal of Magnesium and Alloys 2024年第3期12卷 1009-1020页

作者： Yu Sun Heike Helmholz Regine Willumeit-Römer Institute of Metallic biomaterials Helmholtz-Zentrum HereonGermany

The clinical application of magnesium(Mg)and its alloys for bone fractures has been well supported by in vitro and in vivo ***,there were studies indicating negative effects of high dose Mg intake and sustained local release of Mg ions on bone metabolism or repair,which should not be ignored when developing Mg-based ***,it remains necessary to assess the biological effects of Mg implants in animal models relevant to clinical treatment *** primary purpose of this study was to validate the beneficial effects of intramedullary Mg implants on the healing outcome of femoral fractures in a modified rat *** addition,the mineralization parameters at multiple anatomical sites were evaluated,to investigate their association with healing outcome and potential clinical *** to the control group without Mg implantation,postoperative imaging at week 12 demonstrated better healing outcomes in the Mg group,with more stable unions in 3D analysis and high-mineralized bridging in 2D *** bone tissue mineral density(TMD)was higher in the Mg group at the non-operated femur and lumbar vertebra,while no differences between groups were identified regarding the bone tissue volume(TV),TMD and bone mineral content(BMC)in *** the surgical femur,the Mg group presented higher TMD,but lower TV and BMC in the distal metaphyseal region,as well as reduced BMC at the osteotomy *** component analysis(PCA)-based machine learning revealed that by selecting clinically relevant parameters,radiological markers could be constructed for differentiation of healing outcomes,with better performance than 2D *** study provides insights and preclinical evidence for the rational investigation of bioactive materials,the identification of potential adverse effects,and the promotion of diagnostic capabilities for fracture healing.

关键词： Magnesium Implants Bone fracture Mineralization Systemic modulation Principal component analysis.

Di-PEGylated insulin:A long-acting insulin conjugate with superior safety in reducing hypoglycemic events

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2761-2772页

作者： Zhipeng Zeng Runcheng Tan Shi Chen Haolin Chen Zhijia Liu Lixin Liu Mingqiang Li Yongming Chen Laboratory of biomaterials and Translational Medicine Center for NanomedicineThe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China School of Materials Science and Engineering Center of Functional BiomaterialsKey Laboratory of Polymeric Composite Materials and Functional Materials of Ministry of EducationSun Yat-sen UniversityGuangzhou 510275China

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes,its therapeutic potential is compromised by its short half-life and narrow therapeutic *** long-acting insulin analogs,such as insulin-polymer conjugates,are mainly used to improve pharmacokinetics by reducing renal ***,these conjugates are synthesized without sacrificing the bioactivity of insulin,thus retaining the narrow therapeutic index of native insulin,and exceeding the efficacious dose still leads to ***,we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated *** impairing the binding affinity to the receptor and the activation of the receptor,di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly,increases its maximum tolerated dose *** target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high *** work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events.

关键词： Diabetes Insulin Therapeutic index Hypoglycemia PEGylation Receptor-mediated clearance Half-life Diabetic nephropathy

Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy

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Chinese Chemical Letters 2024年第8期35卷 229-234页

作者： Jin Wang Xiaoyan Pan Junyu Zhang Qingqing Zhang Yanchen Li Weiwei Guo Jie Zhang School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an 710061China center of Advanced Pharmaceuticals and biomaterials State Key Laboratory of Natural MedicineChina Pharmaceutical UniversityNanjing 210009China

Tumor vascular normalization has emerged as a promising strategy for synergistic therapy *** on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic ***,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic ***,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.

关键词： Tumor vasculature normalization Diagnosis and treatment Cytotoxicity Depleting glutathione Ferroptosis Immune activation

Clean production of lactic acid by selective carbon-carbon bond cleavage of biomass feedstock over a novel carbon-bismuth oxychloride photocatalyst

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Frontiers of Chemical Science and Engineering 2024年第2期18卷 69-81页

作者： Zulfiqar Ali Jiliang Ma Dongnv Jin Rui Cui Runcang Sun Liaoning Key Lab of Lignocellulose Chemistry and biomaterials Liaoning Collaborative Innovation Center for Lignocellulosic BiorefineryCollege of Light Industry and Chemical EngineeringDalian Polytechnic UniversityDalian 116034China

The use of functional materials such as carbon-bismuth oxyhalides in integrated photorefineries for the clean production of fine chemicals requires restructuring.A facile biomass-assisted solvothermal fabrication of carbon/bismuth oxychloride nanocomposites(C/BiOCl)was achieved at various *** with BiOCl and C/BiOCl-120,C/BiOCl-180 exhibited higher crystallinity,wider visible light absorption,and a faster migration/separation rate of photoinduced *** the selective C–C bond cleavage of biomass-based feedstocks photocatalyzed by C/BiOCl-180,the xylose conversion and lactic acid yield were 100%and 92.5%,respectively.C/BiOCl-180 efficiently converted different biomass-based monosaccharides to lactic acid,and the efficiency of pentoses was higher than that of ***,lactic acid synthesis was favored by all active radicals including superoxide ion(·O_(2)^(−)),holes(h^(+)),hydroxyl radical(·OH),and singlet oxygen(^(1)O_(2)),with·O_(2)^(−)playing a key *** fabricated photocatalyst was stable,economical,and *** use of biomass-derived monosaccharides for the clean production of lactic acid via the C/BiOCl-180 photocatalyst has opened new research horizons for the investigation and application of C–C bond cleavage in biomass-based feedstocks.

关键词： carbon-carbon bond cleavage biomass reforming C/BiOCl lactic acid photocatalysis

A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

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Nano Research 2024年第6期17卷 5424-5434页

作者： Jinna Ren Jingying Hu Fan Dong Yan Xu Yang Peng Yuping Qian Guanmeng Zhang Min Wang Yuguang Wang Department of Prosthodontics Hospital of StomatologyJilin UniversityChangchun 130021China Department of General Dentistry II Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China center of Digital Dentistry Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Nursing Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China The VIP Department School and Hospital of StomatologyChina Medical UniversityLiaoning Provincial Key Laboratory of Oral DiseasesShenyang 110002China

Cuprotosis,a new type of cell death,provides great opportunities for the treatment of oral squamous cell carcinoma,as nanocarriers of copper ions can induce cuprotosis and immunogenic ***,we studied an editor that enables production of a nanoparticle“storm”in oral squamous cell carcinoma,maximizing the toxic effect of these particles and reprogramming the tumor microenvironment;as a result,T cells and natural killer(NK)cells can infiltrate the tumor microenvironment to activate an antitumor immune *** this basis,the editor can be combined with optical therapy to improve patient *** this study,the metal ratio was regulated in response to the nanocarrier of acid response ***,in the presence of a specific copper ion content,the nanocarrier could change the permeability of the tumor cell *** on these results,the nanoparticles were cracked in an acidic environment and then released copper ***,the nanoparticles contributed to cuprotosis and immunogenic *** addition,the editor could inhibit murine oral cancer 1(MOC1)tumors in C57BL/6 without *** rate of tumor growth inhibition was as high as approximately 80%.This strategy provides a new idea for ***,it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell *** all,this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

关键词： cuprotosis immunogenic death photothermal therapy tumor microenvironment immunotherapy

Peroxidase-like nanozyme based microenvironment-responsive injectable hydrogel for bacteria-infected wound healing

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Science China Technological Sciences 2024年第10期67卷 3247-3260页

作者： ZHOU Wei LI XiaNan TANG MengCheng PAN LingFeng WANG BeiBei ZHANG Hao ZHANG Han WANG ShiBo KONG XiangDong Institute of Smart Biomaterial Materials School of Materials Science and EngineeringZhejiang University of Science & Technology Zhejiang-Mauritius Joint Research center for biomaterials and Tissue Engineering Zhejiang University of Science & Technology

Hydrogel stands out as one of the most attractive wound dressings due to its excellent moisturizing properties and capacity to absorb wound exudates. However, conventional hydrogel dressings often lack responsiveness to the microenvironment, merely acting as protective barriers for the wound. Consequently, they exhibit limited effectiveness in preventing infection and facilitating wound repair. To address these problems, we have developed a multifunctional injectable hydrogel, CF/MS@HG, based on peroxidase-like nanozymes, aiming at rapidly healing bacterial-infected wounds. The hydrogel is mainly composed of oxidized sodium alginate, aminated gelatin, and polylysine, encapsulating MIL-101(CuFe) NPs(CF) and manganese selenide nanoparticles(MnSe2NPs, or MS NPs). After injection, the complex rapidly gelatinizes at the infected wound site through a Schiff base reaction. In vitro experiments have demonstrated the hydrogel's strong adhesion and self-healing ***, CF exhibiting peroxidase(POD)-like activity, catalyzes in situ hydrogen peroxide(H2O2) to generate highly toxic hydroxyl radicals(·OH) within the wound microenvironment, inducing oxidative damage to bacteria. Meanwhile, MS decomposes into H2Se in the slightly acidic wound microenvironment, disrupting bacterial metabolism and inhibiting *** addition of polylysine further enhances the hydrogel's antibacterial properties. In vivo experiments have shown that the hydrogel exhibits excellent biological safety and significantly promotes wound healing. This multifunctional smart hydrogel holds great promise for the treatment of bacterial-infected wounds.

关键词： peroxidase-like nanozyme manganese selenide injectable hydrogel bacterial infection wound healing

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持续释放蒙脱土插层杂化复合材料中的成骨微量元素促进骨再生

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Science China Materials 2024年第7期67卷 2067-2079页

作者：童磊刘泉滢熊丽王培磊赵明达李星梁洁樊渝江张兴栋孙勇 National Engineering Research center for biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610065China Sichuan Testing center for biomaterials and Medical Devices Sichuan UniversityChengdu 610065China

优化支架组分和结构以实现内源性成骨是骨组织工程中一项有前景的进展.本研究将蒙脱土作为一种增强相,以插层结构引入到多巴胺介导的仿生有机/无机杂化水凝胶中.通过蒙脱土-聚合物相互作用和多酚介导的多重反应改善了骨再生支架(HDC-HAp... 详细信息

优化支架组分和结构以实现内源性成骨是骨组织工程中一项有前景的进展.本研究将蒙脱土作为一种增强相,以插层结构引入到多巴胺介导的仿生有机/无机杂化水凝胶中.通过蒙脱土-聚合物相互作用和多酚介导的多重反应改善了骨再生支架(HDC-HAp-MMT)的理化特性,增强了力学性能和抗降解能力.特别是,持续性释放的有益微量元素为成骨微环境提供了关键的成骨生化信号.该水凝胶在体外促进了骨髓间充质干细胞增殖和成骨分化.同时,在异位成骨模型中,显著增强了矿物沉积(30天后机械增强6.91倍);在原位兔颅骨修复实验中,实现了相对于天然骨80.94%的骨体积分数和85.89%的骨密度.该策略可能代表了一种新型的生物活性骨再生支架的制备方法.

关键词： montmorillonite osteogenic elements hybrid com-posites bone regeneration

Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement

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International Journal of Oral Science 2024年第2期16卷 238-250页

作者： Liyuan Chen Huajie Yu Zixin Li Yu Wang Shanshan Jin Min Yu Lisha Zhu Chengye Ding Xiaolan Wu Tianhao Wu Chunlei Xun Yanheng Zhou Danqing He Yan Liu 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 Peking University Hospital of Stomatology Fourth Division BeijingChina

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory *** tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor ***,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains *** this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling *** or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling *** Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on ***,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced ***,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor ***,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

关键词： homeostasis movement thereby