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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Targeting Bacterial Persisters via Reactive Oxygen Species-Generating Hydrogel Microspheres

Yanyang Chen,Tao Ding,Yawei Du,Shifeng Ling,Chen Meng,Pengzhen Zhuang,Ningtao Wang,Yicheng Li,Chen Zou,Jinyong Huang,Yuansheng Wu,Huzhe Liu,Wenguo Cui,Li Cao

The presence of bacterial persisters is a key factor contributing to chronic infection. However, no effective treatment methods are currently available. Thus, a platform is developed, called reactive oxygen species (ROS) bomb, based on microenvironment-adaptive hydrogel microspheres, to oxidize the cell membranes of persisters in chronic periprosthetic joint infection (PJI). Fenton reagent hydroxy iron oxide (FeOOH) and a glucose oxidase (GOx)/calcium phosphate (CaP) acid-responsive shell are sequentially induced on the surface of mesoporous polydopamine (PDA) nanoparticles by the PDA-mediated ion precipitation and interfacial adhesion, followed by the coloaded with glucose into microfluidic hyaluronic acid hydrogel microspheres. Hydroxyl radicals are explosively generated through GOx-mediated glucose oxidase, H 2 O 2 production, and its Fenton-like reactions with FeOOH, which also benefit from the weakly acidic microenvironment around persisters, result in the destruction of bacterial cell membrane, and subsequent overflow of cellular contents such as dsDNA, proteins, and K + . The bactericidal rates of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis persisters are up to 99.14% and 98.96%, and the bacterial loads in lesion location are significantly decreased after ROS bombs treated, effectively alleviated the inflammation and bone resorption damage. This work provides a new strategy toward persisters clearance and shows great application potential in other chronic infection-related diseases.

研究领域: 微生物学 · 药学 · 生物医学工程
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Advanced Science · 2025 · IF 14.1

Nanocapsuled Neutrophil Extracellular Trap Scavenger Combating Chronic Infectious Bone Destruction Diseases

Siying Tao,Yingming Yang,Chenzhou Wu,Jiaojiao Yang,Ziyou Wang,Fangjie Zhou,Kunneng Liang,Yi Deng,Jianshu Li,Jiyao Li

Chronic infectious bone destruction diseases, such as periodontitis, pose a significant global health challenge. Repairing the bone loss caused by these chronic infections remains challenging. In addition to pathogen removal, regulating host immunity is imperative. The retention of neutrophil extracellular traps (NETs) in chronic infectious niches is found to be a barrier to inflammation resolution. However, whether ruining the existing NETs within the local infectious bone lesions can contribute to inflammation resolve and bone repair remains understudied. Herein, a nanocapsuled delivery system that scavenges NETs dual-responsively to near-infrared light as a switch and to NETs themselves as a microenvironment sensor is designed. Besides, the photothermal and photodynamic effects endow the nanocapsules with antibacterial properties. Together with the ability to clear NETs, these features facilitate the restoration of the normal host response. The immunocorrective properties and inherent pro-osteogenic effects finally promote local bone repair. Together, the NET scavenging nanocapsules address the challenge of impaired bone repair in chronic infections due to biased host response caused by excessive NETs. This study provides new concepts and strategies for repairing bone destruction attributable to chronic infections via correcting biased host responses in chronic infectious diseases.

CAS / MDL: 5471-63-6 2564-83-2
研究领域: 医学 · 免疫学 · 生物材料学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-20 · IF 12.6

A novel tetrahedral framework nucleic acid-based antibiotic delivery system: overcoming biofilm barriers to combat chronic infections

Hu Yue,Chen Zhou,Mao Xinggang,Qu Di,Zhai Dongsheng,Li Na,Zhou Shan,Xue Xiaoyan,Li Mingkai

Background Overcoming bacterial biofilm barriers to enhance the efficacy of antibiotics remains a major therapeutic challenge, necessitating the development of efficient and biocompatible drug delivery systems. While framework nucleic acids (FNAs) have emerged as promising candidates for overcoming biological barriers, their biofilm penetration efficiency and mechanistic interactions require systematic exploration. This study evaluates the biofilm-penetrating capacity of FNAs with distinct topological configurations (linear, triangular, and tetrahedral), investigates their antibiotic delivery performance in biofilm-infected models, and elucidates the structure-dependent interactions between FNAs and bacteria. Results DNA tetrahedron (Td) demonstrated superior biofilm penetration, exhibiting 44-fold and 11-fold stronger fluorescence intensity at a biofilm depth of 20 μm compared to linear and triangular counterparts, respectively, while maintaining structural stability. The optimized polymyxin B-loaded Td (PMB@Td, with a PMB: Td ratio of 10:1) enhanced biofilm permeability by 6-fold relative to free PMB. PMB@Td outperformed conventional liposome-encapsulated PMB (PMB@Lipo), achieving half-maximal biofilm eradication concentrations (MBEC 50 ) of 12.8 µM versus 16.3 µM for PMB@Lipo. In murine models of biofilm- associated skin and pulmonary infections, PMB@Td effectively controlled bacterial burden and mitigated inflammatory responses without observable toxicity. Mechanistic studies revealed that the tetrahedral topology facilitated efficient diffusion within the biofilm matrix and enhanced Td adhesion to bacterial membranes. Conclusions This work establishes Td as a robust nanoplatform for overcoming biofilm-mediated antibiotic resistance. The topology-dependent interactions provide critical design principles for engineering next-generation nanocarriers against biofilm-associated chronic infections, with significant translational potential in antibiofilm therapy. Graphical

CAS / MDL: 90-30-2
研究领域: 生物医学工程 · 微生物学 · 药剂学 · 纳米技术
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Facile Formulation of a Resveratrol-Mediated Multibond Network Hydrogel with Efficient Sustainable Antibacterial, Reactive Oxygen Species Scavenging, Pro-Angiogenesis, and Immunomodulation Activities for Accelerating Infected Wound Healing

Jing Feng,Zifei Wang,Xiyu Li,Chongyun Bao,Yu Xiao

The management of chronic infected wounds remains a significant clinical challenge, largely due to the deficiency of optimal wound dressings with adequate mechanical strength, appropriate adhesiveness, and efficient sustainable antibacterial, reactive oxygen species (ROS) scavenging, pro-angiogenesis, and immunomodulation properties. To address such a dilemma, we employed a simple and facile strategy to utilize resveratrol (RSV) as a functional component to mediate hydrogel gelation in this study. The structure of this obtained hydrogel was supported by a multibond network, which not only endowed the resultant product with superior mechanical strength and moderate adhesiveness but also effectively prolonged the bioavailability of RSV. This strategy successfully integrated the entire system with sustainable antibacterial, ROS scavenging, pro-angiogenesis, and immunomodulation properties. Subsequent in vivo evidence has verified that this material was capable to accelerate the healing of chronic infected wounds. The underlying mechanism can be explained that this hydrogel is capable of propelling macrophage polarization from the M1 to M2 phenotype through modulating the PI3K/AKT signaling pathway to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling as well as maintaining the mitochondrial membrane potential level in the normal state under excessive inflammatory and oxidative stimulus. In summary, this multifunctional hydrogel wound dressing provides a feasible way to promote the bioavailability of RSV, which is conducive for preparing a promising candidate for chronic infected wound healing. What is more important, it is also beneficial to reveal the correlative mechanisms to establish advanced therapeutic platform for targeting other complex infection microenvironment.

研究领域: 生物材料学 · 药理学 · 免疫学 · 创伤修复
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Multifunctional PDA/ZIF8 based hydrogel dressing modulates the microenvironment to accelerate chronic wound healing by ROS scavenging and macrophage polarization

Jinhong Cai,Shuhan Liu,Qiuling Zhong,Yifeng Shang,Zhengrong Chen,Yi Yao,Bo Zhou,Feiying Yin,Jinmin Zhao,Li Zheng

An ideal wound dressing has both efficient antimicrobial and anti-inflammatory properties, as well as the potential to regulate the immune microenvironment for the treatment of chronically infected wounds. Herein, a novel multifunctional hydrogel wound dressing (HPZ8) was developed for wound healing by incorporating polydopamine Zeolite Imidazole Framework 8 (PDA-ZIF8) nanoparticles into a dynamic cross-linked network consisting of hydrazide-modified hyaluronic acid (HA-CDH) and oxidized hyaluronic acid (HA-CHO). The results suggested that the HPZ8 hydrogel could be injected into the wound to form a barrier, facilitating tissue adhesion and rapid hemostasis. After loaded with PDA-ZIF8 nanoparticles, the hydrogel exhibited excellent antioxidant and photothermal antimicrobial properties, which could effectively scavenge ROS, reduce oxidative stress and eliminate bacterial infections. Especially, near-infrared (NIR) irradiation strengthened the photothermal therapy (PTT). Besides, HPZ8 hydrogel could release zinc ions to promote cell migration, angiogenesis and M2 polarization of macrophages, accelerating macrophage transition from inflammation to proliferation stages, thus promoting infected wound healing. Therefore, the HPZ8 multifunctional hydrogel dressing has application prospects for the therapy of chronic infected wounds.

研究领域: 生物材料 · 伤口愈合 · 纳米技术 · 生物医学工程 · 免疫学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Polyvalent bacteriophages conjugated with ROS-scavenging nanozymes enhance antibiotic-resistant biofilm disruption and anti-inflammatory therapy

Luokai Wang,Yuexue Mai,Junzheng Zhang,Chujin Ruan,Jiayan Hu,Kai Ye,Yan He,Dongsheng Wang,Lulu Jin,Zhengwei Mao,Chenggang Yi,Pingfeng Yu

The emergence of multidrug-resistant pathogens has created a global public health challenge, demanding the development of efficient and safe therapeutic strategies. Herein, we present a novel nanozyme-armed phage system (PA3@RuO 2 ) designed to combat chronic Pseudomonas aeruginosa infections. This system combines the precision of phage therapy with an anti-inflammatory approach. The phage component, PA3, maintains its ability to specifically target and efficiently lyse a broad spectrum of P. aeruginosa strains. Meanwhile, RuO 2 nanozymes with reactive oxygen species-scavenging capabilities localize to infection sites, mitigating inflammation and hypoxia. This dual action enables bacterial clearance and inflammation reduction while ensuring the biocompatibility of PA3@RuO 2 with healthy tissues. In vivo studies further confirm the effectiveness of PA3@RuO 2 in treating chronic P. aeruginosa -induced wound infections and promoting tissue repair. Overall, these findings suggest that PA3@RuO 2 holds promise for developing non-antibiotic antibacterial therapies and advanced disinfection approaches.

CAS / MDL: 12501-23-4
研究领域: 微生物学 · 噬菌体疗法 · 纳米技术 · 传染病学 · 抗炎研究
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BIOMACROMOLECULES · 2024 · IF 5.5

Dual-Responsive Antibacterial Hydrogel Patch for Chronic-Infected Wound Healing

Jianjun Guo,Liang Yao,Xianqing Wang,Rijian Song,Bo Yang,Daochao Jin,Jianjun Guo,Guohua Wu

Bacterial infections in chronic wounds, such as bedsores and diabetic ulcers, present significant healthcare challenges. Excessive antibiotic use leads to drug resistance and lacks precision for targeted wound treatment. Our study introduces an innovative solution: a near-infrared (NIR) and pH dual-responsive hydrogel patch incorporating regenerated silk fibroin (RSF) and molybdenum dioxide (MoO2) nanoparticles (NPs), offering enhanced mechanical properties, precise drug release, and superior antibacterial efficacy. The dual-responsive hydrogel patch allows for precise control over antibiotic release triggered by NIR light and pH fluctuations, enabling tailored treatment for infected wounds. First, the pH-responsive characteristic matches the alkaline environment of the infected wound, ensuring on-demand antibiotic release. Second, NIR exposure accelerates antibiotic release, enhancing wound healing and providing additional antibacterial effects. Additionally, the patch further blocks bacterial infection, promotes wound repair, and degrades in sync with the healing process, further bolstering the efficacy against wound infections.

研究领域: 生物医学工程 · 材料科学 · 药剂学 · 伤口护理
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MATERIALS & DESIGN · 2022 · IF 9.417

A pain reflex-inspired hydrogel for refractory wound healing

Chuan Guo,Yu Wang,Haoyang Song,Weilong Li,Qingquan Kong,Ye Wu

Promoting refractory wound healing remains a major therapeutic challenge. Here, a pain reflex-inspired hydrogel responsive to inflammatory microenvironmental conditions was developed and used to treat chronically infected diabetic wounds. This material was produced by reacting ε-Polylysine, which exhibits antibacterial properties, with oxidized hyaluronic acid to yield a dynamic Schiff base-crosslinked hydrogel capable of undergoing triggered dissociation in response to the lower microenvironmental pH found within refractory wounds. This hydrogel exhibited intrinsic antimicrobial activity owing to the incorporation of ε-Polylysine within the hydrogel network. To imbue the hydrogel with low pH-inducible anti-inflammatory and angiogenic activity, Schiff base bonds were used to capture Deferoxamine (DFO)-loaded amino-functionalized mesoporous silica nanoparticles (MSNs-NH 2 @DFO) on this hydrogel skeleton. The reflexive behaviors of the hydrogel make it ideally suited to facilitating wound healing in response to excessive local inflammation. The resultant intelligent hydrogel was highly biocompatible and exhibited robust antibacterial, anti-inflammatory, and pro-angiogenic activity in vitro and in vivo, thus effectively promoting the healing of chronically infected diabetic wounds. This novel hydrogel therefore holds great promise as a tool to promote refractory wound healing.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 药学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 18 ·9016 · IF 4.9

Biphasic Adaptations of Gastric Epithelial Cells in Chronic H. pylori Infection from Stress to Tolerance

Xiulin Zhang,Yang He,Xiaolu Zhang,Ziyi Liang,Wendong Wang,Zhenyu Da,Jianyi Lv,Meng Guo,Xueyun Huo,Xin Liu,Jing Lu,Lixue Cao,Xiaoyan Du,Zhongming Ge,Zhenwen Chen,Xuancheng Lu,Jianzhong Zhang,Changlong Li

Helicobacter pylori(H. pylori) is a well-known pathogen associated with chronic gastric infection, progressing from gastritis to gastric adenocarcinoma, but the dynamic phenotypic and molecular characteristics of gastric epithelial cells during sustained infection remain unclear. We established a chronic infection model using the human gastric epithelial cell line GES-1, exposed toH. pylorior its lysate across 30 generations, dynamically assessing cell proliferation, migration, invasion, apoptosis, autophagy, and epithelial–mesenchymal transition (EMT) markers, with RNA sequencing for transcriptomic changes and a Mongolian gerbil model to validate chronic pathological progression. AcuteH. pyloriexposure induced pronounced morphological changes; suppressed proliferation, migration, and invasion; triggered apoptosis; and blocked autophagic flux, while long-term stimulation reversed these effects. EMT markers showed progressive loss of epithelial characteristics with chronic infection. RNA sequencing revealed a dynamic shift from inflammation-driven apoptosis to adaptive survival mechanisms. In vivo, prolonged infection induced dynamic TLR expression alongside progressive gastric pathology, including atrophy and dysplasia. Our study provides new molecular evidence for dynamic cellular and immunological adaptations of gastric epithelial cells under chronicH. pyloriinfection, highlighting critical intervention windows for preventing gastric carcinogenesis.

CAS / MDL: 548-62-9
研究领域: 微生物学 · 胃肠病学 · 分子生物学 · 传染病学 · 癌症研究 · 细胞生物学
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BIOMATERIALS · 2021 · IF 12.479

A bioinspired hierarchical nanoplatform targeting and responding to intracellular pathogens to eradicate parasitic infections

Yunjian Yu,Jie Li,Yufei Zhang,Zhuang Ma,Haonan Sun,Xiaosong Wei,Yayun Bai,Zhongming Wu,Xinge Zhang

Intracellular bacteria-mediated antibiotic tolerance, which acts as a “Trojan horse,” plays a critical and underappreciated role in chronic and recurrent infections. Failure of conventional antibiotic therapy is often encountered because infected cells prevent drug permeation or the drug concentration is too low at the site of resident bacteria. New paradigms are therefore urgently needed for intracellular anti-infective therapy. Here, a novel therapeutic was developed for targeted delivery of antibiotics into bacteria-infected macrophages to improve drug accumulation in intracellular niches and bactericidal activity of antibiotics against intracellular pathogens. This hierarchical nanoplatform includes a glycocalyx-mimicking shell that enables rapid uptake by macrophages. Subsequently, the targeting moieties are activated in response to the bacteria, and the release of entrapped antibiotics is triggered by bacteria and bacteria-secreted enzymes . The self-immolative drug delivery nanoplatform eliminates intracellular pathogenic bacteria residing in macrophages more efficiently compared to drugs alone. The in vivo dynamically monitored nanosystem also efficiently inhibited the growth of intracellular Staphylococcus aureus in infected muscles of mice with negligible systemic toxicity. The novel dual-targeting design of an all-in-one therapeutic platform can be used as an alternative strategy to reanimate antibiotic therapy against multifarious intracellular bacterial infections.

研究领域: 纳米技术 · 药学 · 传染病学 · 生物医学工程
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MATERIALS & DESIGN · 2022 · IF 9.417

A refractory wound healing hydrogel with integrated functions of photothermal anti-infection, superoxide dismutase mimicking activity, and intelligent infection management

Chuan Guo,Yu Wang,Hui Liu,Ye Wu,Yi Wang,Zhenxing Cao,Weilong Li,Yan Peng,Hui Xiong,Biqiang Jin,Qingquan Kong,Jinrong Wu

Promoting refractory wound healing remains a challenging issue. Currently, dressings with intelligent infection management functions built on infection eradication and reactive oxygen species (ROS) scavenging abilities are lacking. In this study, an approach based on Cu2 + -imidazole coordination cross-linked histidine grafted chitosan (CS-His) and carbon quantum dots (CQDs) was developed to engineer superoxide dismutase (SOD) mimicking centers with photothermal anti-infection and intelligent anti-infection abilities, beyond typical ROS scavenging activity. The cross-linked coordination network was further promoted with tanshinol-encapsulated ZIF-8 frameworks ( [email protected] ) to achieve intelligent infection management behaviors. These designs generate a refractory wound-healing hydrogel with integrated functions of photothermal anti-infection, SOD mimicking activity, and intelligent infection management. In response to infection exacerbation, the SOD mimicking centers and [email protected] nanoparticles could release CQDs for anti-infection and Ts for antioxidation, respectively. In vitro results revealed photothermal anti-infection, ROS scavenging, and intelligent infection management capacities of the hydrogel. These abilities promoted the M2 transformation of macrophages and rescued the inhibitory effect of infection on fibroblast proliferation and migration. The hydrogel exhibited high regenerative efficacy in a rat model of chronically infected diabetic wounds. These results demonstrated the immense potential of the intelligent hydrogel integrated with multifunctions for refractory wound healing.

研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 纳米技术 · 药学
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Advanced Healthcare Materials · 2025 · IF 9.6

A Multifunctional Janus Electrospinning Dressing with Sequential Drug-releasing Property for Programmed Treatments of Chronic Infected Wounds

Zhi Qu,Yang Wang,Zequan Liu,Wenzhan Fu,Xinmeng Li,Shenglin Ma,Lingwan Hao,Yu Wang,Weihua Liu,Rujian Jiang

Wound dressings equipped with disinfection and wound tissue regeneration capabilities demonstrate significant potential in chronic wound management. However, current multifunctional dressings can rarely accommodate multiple repair processes accurately due to the time-dependent variational wound microenvironment. Herein, a Janus wound dressing is developed based on electrospun nanofibrous scaffold featuring programmed drug release performance and asymmetrical wettability. Specifically, polyvinylidene fluoride (PVDF) nanofiber membrane as the outer layer to resist the external biofouling and provide essential mechanical support for the inner layer was firstly constructed. Subsequently, the inner layer composed of polyvinyl pyrrolidone (PVP) and polylactic acid (PLA) fibers which are separately loaded with bacterial-targeted nanoparticles (VHA NPs) and composite particle of zeolite imidazolate frameworks-8 containing deferoxamine (ZD NPs) is fabricated on the PVDF membrane. Experimental results demonstrated that the degradation rate of the inner layer could be precisely controlled to sequentially deliver the loaded drugs into the wound site. Taking advantages of the synergistic therapeutic effects including significant antibacterial activity, admired antioxidant property and remarkable angiogenesis performances, the fabricated Janus dressing (PF/PHPD) achieves superior performance for promoting infected wound healing in a full-thickness skin wound model, much better than that of conventional bandage and clinical antibiotic treated wound.

CAS / MDL: 1898-66-4
研究领域: 生物材料 · 组织工程 · 伤口愈合 · 纳米技术 · 药物递送系统 · 生物医学工程
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