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ACS Nano · 2025 · IF 16

Cecropin A-Derived Peptide for the Treatment of Osteomyelitis by Inhibiting the Growth of Multidrug-Resistant Bacteria and Eliminating Inflammation

Ziao Zhou,Peng Zhang,Dinghao Chen,Nan Kong,Huayang Liu,Juan Liang,Kai Huang,Huaimin Wang

Osteomyelitis poses substantial therapeutic challenges due to the prevalence of multidrug-resistant bacterial infections and associated inflammation. Current treatment regimens often rely on a combination of corticosteroids and antibiotics, which can lead to complications and impede effective bacterial clearance. In this study, we present CADP-10, a Cecropin A-derived peptide, designed to target methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MRE), while simultaneously addressing inflammatory responses. CADP-10 self-assembles into nanobacterial net (NBacN) that selectively identify and bind to bacterial endotoxins (LPS and LTA), disrupting membrane integrity and depolarizing membrane potential, which culminates in bacterial death. Importantly, these NBacN are bound to LPS and LTA from dead bacteria, preventing their engagement with TLR receptors and effectively blocking downstream inflammatory pathways. Our assessments of CADP-10 demonstrate good biosafety in both in vitro and in vivo models. Notably, in a rabbit osteomyelitis model, CADP-10 eliminated MRSA-induced bone infections, mitigated inflammation, and promoted bone tissue regeneration. This research highlights the potential of CADP-10 as a multifunctional antimicrobial agent for the management of infectious inflammatory diseases.

研究领域: 微生物学 · 感染病学 · 药理学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Bacterial-targeting liposomes for synergistic nitric oxide/methicillin therapy in MRSA-infected osteomyelitis

Kai Lv,Zhen Wang,Wenjun He,Zijing Feng,Hui Xing,Yuanfang Jiang,Yingtong Lu,Jingjie Shang,Bin Guo,Hao Xu,Guowei Li,Bo Ning,Dong Ma

Nitric oxide (NO) as a promising therapeutic molecule for infection treatments is impeded by challenges of precise delivery and accumulation in treating deep tissue infections, such as osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Herein, a bacterial-targeting liposome (MN@Mal-Lips) assembled by maltotriose (Mal)-modified cholesterol and lecithin was presented for synergistic NO/methicillin (MET) therapy of MRSA-infected osteomyelitis. MN@Mal-Lips were specifically internalized by MRSA via Mal transporters and thus targetedly accumulated at deep MRSA-infected site. Attributed to the capabilities of NO to induce biofilm dispersal and reverse bacterial resistance, the precisely delivered NO combined with MET facilitating efficient bacterial eradication by disrupting bacterial cell membrane and damaging bacterial DNA. Furthermore, MN@Mal-Lips relieved the local inflammation by potentiating the polarization of macrophages to M2-type while suppressing the M1-type. Meanwhile, MN@Mal-Lips promoted the proliferation, migration, and mineralization of osteoblast, as well as upregulated osteogenesis-related genes, thus repairing the bone tissue. Together, this bacterial-targeting NO-delivery liposome system offers an effective therapeutic strategy for clinical management of MRSA-induced osteomyelitis and may provide great possibilities in the development of NO therapy combating with deep tissue infections caused by drug-resistant bacteria.

研究领域: 药学 · 微生物学 · 医学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Diverse loss mechanism enhanced microwave thermal effects of capacitor-like structure Ti3C2Tx MXene/CNT for rapid treatment of osteomyelitis

Mingxue Shi,Liguo Jin,Chaofeng Wang,Congyang Mao,Xiangmei Liu,Zhaoyang Li,Shengli Zhu,Hui Jiang,Zhenduo Cui,Yufeng Zheng,Shuilin Wu

Compared to phototherapy, microwave therapy has emerged as a promising approach for the treatment of deeply tissue-infected osteomyelitis owing to deep penetration ability, precise positioning heating, low damage to normal tissue. However, it is still significant to design materials with efficient microwave thermal conversion. In this paper, capacitor-like structure Ti 3 C 2 T x MXene/CNT is prepared to achieve high microwave thermal conversion efficiencies for safe and efficient microwave therapy through mechanisms associated with polarization and induced electric fields. Ti 3 C 2 T x MXene/CNT have been shown to achieve significant microwave thermal effects at varying thicknesses of tissue barrier and can rapidly increase the temperature in a short period of time, effectively causing 98.80% eradication of Staphylococcus aureus and 99.24% eradication of Escherichia coli within 20 min. Combined with remarkable antimicrobial effect and acceptable biocompatibility, this may provide reference for the safe and effective microwave therapy strategies to treat osteomyelitis.

CAS / MDL: 7789-24-4
研究领域: 医学 · 材料科学
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ADVANCED MATERIALS · 2023 ·Vol. 35 ·期 13 ·2210296 · IF 29.4

Achieving Fast Charge Separation by Ferroelectric Ultrasonic Interfacial Engineering for Rapid Sonotherapy of Bacteria-Infected Osteomyelitis

Jianfang Li,Xiangmei Liu,Yufeng Zheng,Zhenduo Cui,Hui Jiang,Zhaoyang Li,Shengli Zhu,Shuilin Wu

Bacteria-infected osteomyelitis is life-threatening without effective therapeutic methods clinically. Here, a rapid and effective therapeutic strategy to treat osteomyelitis through ferroelectric polarization interfacial engineering of BiFeO 3 /MXene (Ti 3 C 2 ) triggered by ultrasound (US) is reported. Under US, the ferroelectric polarization induces the formation of the piezoelectric field. US cavitation effect induced sonoluminescence stimulates BiFeO 3 /Ti 3 C 2 to produce photogenerated carriers. With synergistic action of the polarization electric field and Schottky junction, BiFeO 3 /Ti 3 C 2 accelerates the separation of electrons and holes and simultaneously inhibits the backflow of electrons, thus improving the utilization of polarized charges and photogenerated charges and consequently enhancing the yield of reactive oxygen species under US. As a result, 99.87 ± 0.05% of Staphylococcus aureus are efficiently killed in 20 min with the assistance of ultrasonic heating. The theory of ferroelectric ultrasonic interfacial engineering is proposed, which brings new insight for developing ferroelectric ultrasonic responsive materials used for the diagnosis and therapy of deep tissue infection and other acoustoelectric devices.

研究领域: 医学 · 材料科学 · 生物工程
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ACS Nano · 2025 · IF 16

Antibacterial Peptides-Produced Cell Hydrogel Eliminates Intracellular Pathogens and Remodels Immune Microenvironment for Osteomyelitis Therapy

Yu Chen,Qi-Wen Chen,Fang-Sheng Fu,Jian-Hua Yan,Junwei Su,Xian-Zheng Zhang,Aixi Yu

Featuring bacterial invasion and colonization within cells, chronic infection-induced immune suppression, and inflammatory cell infiltration, osteomyelitis is currently an intractable and recurrent bone disease. In this study, an injectable hydrogel that gels in situ and is loaded with engineered antimicrobial cells (LL37-MSC@OCAHM) is developed. This anti-inflammatory hydrogel not only maintains cell activity in the inflammatory environment but also releases magnesium ions (Mg2+) to promote the differentiation of MSCs into bone-forming cells, contributing to bone mass formation, enhancing bone repair, and accelerating bone healing. The engineered cells continuously produce antimicrobial peptides of LL37, which effectively kill both extracellular and intracellular bacteria at the osteomyelitis site. Additionally, cell hydrogel also modulates the immune response by shifting the osteomyelitis environment from pro-inflammatory to anti-inflammatory, reducing the infiltration of immune cells and myeloid-derived suppressor cells (MDSCs). We also demonstrated its ability to activate immune responses and generate immune memory, thereby preventing the recurrence of secondary infections. This study introduces an engineered cell-based approach that combines active antimicrobial effect, immune modulation, and bone repair, for effectively eliminating osteomyelitis infections and preventing recurrence.

研究领域: 医学 · 生物材料学 · 免疫学
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COMPOSITES PART B-ENGINEERING · 2023 · IF 13.1

Dual-functional borosilicate glass (BSG) delivery implant for osteomyelitis treatment and bone regeneration

Hao Zhang,Li Li,Lei Chu,Jing Huang,Xiaochen Chen,Xianglong Zhuo,Yulin Wang,John Robert Honiball,Bin Wang,Wei Chen,William W. Lu,Deping Wang,Bing Li,Xu Cui,Haobo Pan

Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo . However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo . Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.

研究领域: 材料科学 · 生物医学工程 · 药学 · 再生医学
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Advanced Science · 2024 · IF 14.3

Emodin Enhanced Microwave-Responsive Heterojunction with Powerful Bactericidal Capacity and Immunoregulation for Curing Bacteria-Infected Osteomyelitis

Tao Xu,Hao Cheng,Hailiang Pei,Jiameng Wang,Yiwei Shi,Xiangyu Zhang,Di Huang

Eradication of osteomyelitis caused by bacterial infections is still a major challenge. Microwave therapy has the inherent advantage of deep penetration in curing deep tissue infections. However, the antibacterial efficiency of sensitizers is limited by the weak energy of microwaves. Here, a hybrid heterojunction system (Fe 3 O 4 /CuS/Emo) is designed for curing bacterially infected osteomyelitis. As an enhanced microwave sensitizer, it shows supernormal microwave response ability. Specifically, Fe 3 O 4 acts as a matrix to mediate magnetic loss. After CuS loading, the heterogeneous interface forms induce significant interfacial polarization, which increasing dielectric loss. On the basis of the heterojunction formed by the two semiconductors, emodin is innovatively introduced to modify it. This integration not only accelerates the movement of charge carriers but also enhances polarization loss due to the numerous functional groups present on the surface. This further optimizes the microwave thermal and catalytic response. In addition, the unique anti-inflammatory properties of emodin confer the ability of hybrid heterojunction to regulate the immune microenvironment. In vivo studies reveal that heterojunction modified by emodin programmed elimination of bacteria and regulation of the immune microenvironment. It offers a revolutionary approach to the treatment of bacterial osteomyelitis.

CAS / MDL: 7757-82-6
研究领域: 医学 · 材料科学
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JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY · 2025 · IF 14.3

Multivariant interfacial/ferroelectric/dipole polarization strengthened microwave-catalysis eradicates deep bacteria-infected osteomyelitis

Liguo Jin,Hanpeng Liu,Congyang Mao,Chaofeng Wang,Shuilin Wu,Khin Wee Lai,Yu Zhang,Zhaoyang Li,Shengli Zhu,Hui Jiang,Zhenduo Cui,Jie Shen,Yufeng Zheng,Xiangmei Liu

Osteomyelitis is a state of inflammation caused by pathogens with progressive bone destruction. In critical conditions, osteomyelitis can result in limb necrosis, dysfunction, and permanent disability. Traditional treatments for osteomyelitis usually include antibiotics and surgical debridement. However, overuse of antibiotics can result in bacterial resistance and serious side effects. In this paper, a microwave (MW)-responsive composite MoS 2 /Bi 2 S 3 /BaTiO 3 was constructed from flaky nanoflower molybdenum disulfide (MoS 2 ), rod-shaped bismuth sulfide (Bi 2 S 3 ), and bulk barium titanate (BaTiO 3 ) for the ‌therapy of bacteria-infected osteomyelitis. Under MW irradiation, MoS 2 /Bi 2 S 3 /BaTiO 3 could generate MW heat and reactive oxygen species (ROS), and its MW thermal response mechanism was investigated by MW vector analysis, which showed that the MW thermal response performance of MoS 2 /Bi 2 S 3 /BaTiO 3 was devoted to the reflection loss, dielectric loss, and suitable impedance matching and attenuation constants induced by the interfacial polarization, dipole polarization, and ferroelectrode polarization. Under MW irradiation, due to strong electromagnetic field enhancement parameters and low oxygen adsorption energy, MoS 2 /Bi 2 S 3 /BaTiO 3 could form a heterogeneous interface to accelerate charge transfer, resulting in ROS. The antibacterial mechanism of MoS 2 /Bi 2 S 3 /BaTiO 3 was investigated by bacterial transcriptome RNA sequencing analysis, which indicated that MoS 2 /Bi 2 S 3 /BaTiO 3 had excellent antibacterial properties.

研究领域: 医学 · 生物工程 · 材料科学
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ACS Biomaterials Science & Engineering · 2023 · IF 5.8

Dielectric and Magnetic Composites of Fe3O4@APNs for Superior Microwave Thermal Effect

Yan-lei Zhan,Kai-chao Wen,Zheng-an Li,Ping Sun,Feng-qian Li

As for the deep tissue infections of chronic osteomyelitis, antibiotics are hard to deliver into the infected bone tissue, which makes it difficult to be cured completely in clinic. Microwave has strong penetration, and the medium can produce a good bactericidal effect through the microwave thermal effect (MTE). Here, a new microwave sensitizer (Fe3O4@APNs) was prepared and evaluated. Black phosphorus nanosheets modified with phytic acid dodecasodium (APNs) were fabricated by a liquid-phase exfoliation method that exhibited good water oxygen stability. A complex with Fe3O4 compound and APNs (Fe3O4@APNs) was formed by an ultrasonic mixing process, which showed excellent MTE (quickly increased to 53.5 °C in 5 min at 2.45 GHz, 10 W/cm2) via dielectric versus magnetic loss (reflect loss value of −5.94 dB at 2.45 GHz). The Fe3O4@APNs microwave sensitizer developed in this study has an outstanding in vitro antibacterial effect and might show promise for the treatment of chronic osteomyelitis enabled by local tissue heating via the MTE.

CAS / MDL: 68-12-2
研究领域: 材料科学 · 医学 · 生物医学工程
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Applied Nanoscience · 2021 ·Vol. 11 ·期 10 ·2549-2560 · IF 3.674

Fabrication of ultrasound-mediated cerium oxide nanoparticles for the examinations of human osteomyelitis and antibacterial activity

Dai Xiusong,Wang Xiaopan,Chen Xiaotian,Ye Longfei,Wu Min

In this work, two Gram-negative and three Gram-positive pathogenic pathogens were examined for the antibacterial activity of cerium oxide nanoparticles. CeO 2 nanoparticles (CeO 2 NPs) encapsulation with hydroxyapatite and chitosan were synthesised using the precipitation procedure and simultaneous reactant addition by techniques of a Wet Chemical Synthesis approach. Thermal analyses (TG–DTA), their degradation processes and their synthesis of CeO 2 NPs were investigated, and the precursor powders were acquired. Fourier transform infrared (FTIR), X-ray diffraction, Raman spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS) examined the thermally treated sample’s composition, structure, and morphology. CeO 2 NPs antioxidant has also been determined. The analysis against five diseased pathogens, including Bacillus cereus, Staphylococcus aureus , Listeria monocytogenes , Salmonella typhimurium and Escherichia coli , has been performed on both fluid growth mediums. The growth inhibition of cerium oxide nanoparticles in all five pathogens studied exhibited noteworthy results. This study underlines the CeO 2 NPs, which revealed considerable changes in antibacterial activity because of the changes in membrane structure and the composition of cell walls across the two test groups. As a result, generated CeO 2 NPs can be prospective osteomyelitis therapy candidates.

研究领域: 医学 · 材料科学 · 微生物学
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Journal of Materials Chemistry B · 2025 · IF 5.7

Multifunctional metal–phenolic nanoparticles with antibacterial and anti-inflammatory effects for osteomyelitis management

Qinsheng Hu,Chengcheng Wu,Ling Wang,Dan Cao,Junchao Wang,Yangrui Du,Miao Liu,Kaijun Li

Osteomyelitis is a serious inflammatory disease mostly caused by bacterial infections. It is necessary to simultaneously eradicate bacterial cells and inhibit inflammation in treating osteomyelitis. Herein, we design an innovative zinc ion (Zn2+)-based nano delivery system for the management of osteomyelitis. Taking advantage of the coordination self-assembly of Zn2+, quercetin (QU), and ε-poly-L-lysine (EPL), Zn2+-containing nanoparticles (denoted as ZQE NPs) are prepared. ZQE NPs are spherical nanoparticles with amorphous structures. They are stable in the physiological neutral environment but can be dissociated in an acidic microenvironment of infection sites. Since Zn2+ is encapsulated into ZQE NPs by coordination interaction, the deactivation of Zn2+ by proteins can be effectively avoided. Therefore, ZQE NPs can maintain excellent bactericidal activity in a protein-rich environment, while dissociative Zn2+ doesn’t exhibit obvious bactericidal ability. Meanwhile, ZQE NPs are highly effective at scavenging intracellular reactive oxygen species (ROS) and inhibiting pro-inflammatory cytokines, due to the strong anti-inflammatory effects of QU and Zn2+. The in vivo therapeutic efficacy of ZQE NPs is assessed using a rat model of methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis. Results demonstrate that ZQE NPs effectively eradicate bacterial cells and reduce inflammation in vivo, thereby promoting osteogenesis and recovery of osteomyelitis.

CAS / MDL: 117-39-5
研究领域: 医学 · 材料科学 · 生物化学
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ACS Nano · 2022 · IF 18.027

Piezo-Augmented Sonosensitizer with Strong Ultrasound-Propelling Ability for Efficient Treatment of Osteomyelitis

Xiaobo Feng,Liang Ma,Jie Lei,Qunle Ouyang,Yuxuan Zeng,Yue Luo,Xiaoguang Zhang,Yu Song,Gaocai Li,Lei Tan,Xiangmei Liu,Cao Yang

The successful treatment of osteomyelitis remains a great challenge in the field of orthopedics. The clinical method for treating refractory bone infection requires a combination therapy of long-term systemic antibiotics administration and surgical debridement. It is highly desirable to develop an antibiotic-free, noninvasive, rapid strategy to eradicate osteomyelitis. Herein, we fabricate a piezoelectric-enhanced sonosensitizer that consists of a porphyrin-based hollow metal–organic framework (HNTM), MoS2 nanosheets, and a red cell (RBC) membrane. We find that the ultrasound (US)-induced piezoelectric polarization of MoS2 can improve the charge transfer of HNTM at the heterointerface of HNTM-MoS2, increasing the production of reactive oxygen species (ROS). Besides, MoS2 increases the asymmetric shape of HNTM, leading to the strong US-propelling ability of HNTM–MoS2. The produced ROS and strong mechanical force can kill methicillin-resistant Staphylococcus aureus (MRSA) with an antibacterial efficiency of 98.5% under 15 min of US treatment, resulting in intracellular DNA damage and increased oxidative stress and disturbance of purine metabolism, tryptophan metabolism, and pantothenate and CoA biosynthesis of MRSA. Together with the toxin neutralization ability, the RBC-HNTM-MoS2 successfully eliminates the bone infection and suppresses inflammation and bone loss. This work provides another strategy for developing an efficient sonosensitizer through piezoelectric-assisted sonocatalysis and enhancing US-propelling ability.

研究领域: 生物医学工程 · 感染病学 · 材料科学
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