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Advanced Healthcare Materials · 2025 · IF 9.6

Engineered Curcumin/Strontium Nanoparticles Grafted with K6-CAMEL0 Peptide for the Multifaceted Treatment of Bone Infections

Zeyu Shou,Dong Yang,Yewen Liu,Jiawei Yu,Jiali Shou,Ming Cai,Lianxin Li,Shuohui Yuan,Xiufeng Wang

To address the clinical challenges of bacterial infection, inflammation, oxidative stress, ischemia-hypoxia, and excessive bone resorption during infected bone therapy, a multifunctional nanoparticle (Cur/Sr@CAMEL0 NPs) is engineered by integrating a self-assembled curcumin-strontium metal-phenolic network core (Cur/Sr NPs) with a hexameric lysine-conjugated antimicrobial peptide (K6-CAMEL0) via surface modification. The resultant nanoparticle exhibits distinctive morphological and structural characteristics, along with favorable cellular compatibility. Functionally, it is demonstrated to exhibit broad-spectrum antibacterial activity, along with inflammation and reactive oxygen species (ROS) scavenging capabilities, pro-angiogenic effects, and significant promotion of necrotic bone resorption and normal bone regeneration. In an infected bone defect animal model, the composite nanoparticle effectively eradicated Staphylococcus aureus ( S. aureus ) colonization and facilitated the bone regeneration process through single-dose administration. These findings collectively highlight the therapeutic potential of Cur/Sr@CAMEL0 as a multifunctional platform for managing bone infections, offering a promising strategy to address complex challenges in infected bone diseases.

CAS / MDL: 1185-53-1 127-09-3
研究领域: 生物材料学 · 骨科学 · 纳米医学 · 感染性疾病 · 炎症生物学 · 组织工程 · 药剂学 · 转化医学
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CERAMICS INTERNATIONAL · 2022 · IF 5.532

pH-responsive drug release and antibacterial activity of chitosan-coated core/shell borate glass-hydroxyapatite microspheres

Rongyu Zhang,Jingxin Ding,Xiaoyu Lu,Aihua Yao,Deping Wang

Multifunctional drug delivery system that can treat bone infection and concurrently accelerate bone tissue regeneration is highly desirable. In this study, we developed a pH-responsive local drug carrier in which a core/shell microsphere consisting of a borate glass core and a mesoporous hydroxyapatite HA shell (BG-HA) was coated with glutaraldehyde-crosslinked chitosan (CS). At neutral pH, a negligible concentration of vancomycin was released from the [email protected] microspheres. However, in an acidic environment, the pores on the HA shell were uncapped due to the swelling of CS, thus accelerating the drug release. The advantage of the [email protected] was evidenced by comparing with [email protected] that was prepared by fully converting borate glass followed by CS coating. The dissolution of the unconverted borate glass core upon immersing in PBS led to an increase in the local pH. This change of pH regulated the swelling/de-swelling behaviours of CS, thereby realizing more sustained drug release. Furthermore, it revealed that the vancomycin-loaded [email protected] provided highly effective antibacterial activity against S. aureus and E. coli , while the vancomycin-loaded [email protected] did not show inhibitory effect on E. coli . The results indicated that the [email protected] would be a promising multifunctional delivery system that can achieve self-regulated drug release, control the acidic environment of bone infection sites and promote bone tissue regeneration.

研究领域: 材料科学 · 生物医学工程 · 药剂学
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Biomedical Materials · 2022 ·Vol. 17 ·期 6 ·065023 · IF 4.103

ZnO nanoparticle modified chitosan/borosilicate bioglass composite scaffold for inhibiting bacterial infection and promoting bone regeneration

Dewei Qiu,Ping Zhou,Jiawei Kang,Zhijun Chen,Zhiyong Xu,Hanwen Yang,Jun Tao,Fanrong Ai

The treatment of implant-associated bone infection remains a significant clinical challenge. However, bone scaffolds with antimicrobial activity and osteoinductive properties can prevent these infections and improve clinical outcomes. In this study, borosilicate bioglass and chitosan composite scaffolds were prepared, and then the surface was modified with nano-zinc oxide. In vitro and in vivo experiments showed that the chitosan/borosilicate bioglass scaffolds have good degradation and osteogenic properties, while the oxidized Zinc scaffolds have better antibacterial properties.

研究领域: 材料科学 · 生物医学工程 · 组织工程 · 生物材料
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COMPOSITES PART B-ENGINEERING · 2024 · IF 12.7

Surface-activated 3D-printed PEEK implant enhances anti-infection and osteogenesis

Zhaolong Wang,Zhou Yu,Zhaoyi Wang,Shifen Li,Liang Song,Tiesong Xu,Guocheng Shen,Yuchen Wang,Tingben Huang,Xiaofei Dong,Guoli Yang,Changyou Gao

With the advantage of remarkable mechanical processing ability without losing its strength , polyetheretherketone (PEEK) based medical devices have been drawing great attention in orthopedic treatments. However, its limited osseointegration capacity and susceptibility to bacterial colonization-induced infections pose a considerable risk of implant failure. Current methods of antimicrobial and osteogenic functionalization frequently exhibit conflicting outcomes. The antimicrobial functionalization of implants usually leads to cytotoxicity and histotoxicity, adversely affecting the connection with surrounding tissues, whereas the osteogenic functionalization may inadvertently promote bacterial adhesion and biofilm development. Therefore, it is highly demanded to endow the PEEK implants with antibacterial and osseointegration properties simultaneously. In this study, 3D-printed PEEK implants were surface modified with hyperbranched poly- l -lysine (HBPL) via physisorption (PEEK- a -HBPL) and chemical grafting (PEEK- g -HBPL), respectively, which were demonstrated by attenuated total reflection Fourier transform infrared spectroscopy, water contact angle, and X-ray photoelectron spectroscopy. Remarkably, both the PEEK- a -HBPL and PEEK- g -HBPL exhibited significantly improved antibacterial efficacy against S. aureus and E. coli , while their osteogenesis ability was not affected but even promoted in vitro . In an in vivo bone-infection and implantation model in rats, significantly reduced surrounding tissue inflammation and larger new bone formation were observed in both the PEEK- a -HBPL and PEEK- g -HBPL groups compared to the untreated PEEK group. This comprehensive study lays a foundation for the advancing of organic orthopedic implant materials, offering potential solutions to the pressing issues of osseointegration deficits and implant-related infections.

研究领域: 骨科 · 生物材料 · 组织工程 · 生物医学工程
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Small · 2019 ·Vol. 16 ·期 4 ·1905185 · IF 10.856

Dual Functional Monocytes Modulate Bactericidal and Anti-Inflammation Process for Severe Osteomyelitis Treatment

Miusi Shi,Peng Zhang,Qin Zhao,Kailun Shen,Yun Qiu,Yin Xiao,Quan Yuan,Yufeng Zhang

Osteomyelitis is an inflammatory bone disease caused by infection microorganisms which leads to progressive bone destruction and loss. Drug resistance and inflammatory damage make it urgent to develop new dual-functional therapies. Based on the powerful bactericidal effect of monocyte/macrophage cells by nature, a functional monocyte with programed anti-inflammatory ability is promising for osteomyelitis treatment. Herein, gold nanocage (GNC)–modified monocytes are developed which contain aspirin to realize the controlled antibacterial and anti-inflammatory process for bone infection treatment effectively. Aspirin@GNC-laden monocytes inherit the biological functions of origin monocytes such as chemotaxis to bacteria, differentiation potential, and phagocytic ability. The controlled release of aspirin from GNC has a beneficial effect on improving the rate and amount of bone regeneration after the anti-infection stage due to its ability to suppress the activity of natural immunity and induce osteoblast differentiation during the treatment of osteomyelitis. The present work described here is the first to utilize living monocytes to achieve a dual effect to antibacteria and anti-inflammation in a time-oriented and programed way, and provides an inspiration for future therapy based on this concept.

CAS / MDL: 107-21-1
研究领域: 生物医学工程 · 纳米技术 · 传染病学 · 免疫学 · 药理学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Study on injectable silver-incorporated calcium phosphate composite with enhanced antibacterial and biomechanical properties for fighting bone cement-associated infections

Huiling Liu,Peng Li,Ziniu Tang,Haoran Liu,Rui Zhang,Jun Ge,Huilin Yang,Xinye Ni,Xiao Lin,Lei Yang

Although commonly used in orthopedic surgery, bone cements often face a high risk of post-operative infection. Developing bone cement with antibacterial capability is an effective path for eliminating implant-associated infections. Herein, the potential of silver ions (Ag + ) and silver nanoparticles (AgNPs) in modifying CPC for long-term antibacterial property was investigated. Ag + ions or AgNPs of various concentrations were incorporated in starch-modified calcium phosphate bone cement (CPB) to obtain Ag + -containing (Ag + @CPB) and AgNPs-containing ( [email protected] ) bone cements. The results showed that all silver-containing CPBs had setting times of about 25–40 min, compressive strengths of greater than 22 MPa, high cytocompatibility but inhibitory effect on Staphylococcus aureus growth. After soaking for 1 week, the mechanical properties and the cytocompatibility of all cements revealed no significant changes, but only CPB with a relatively high content of Ag + (H-Ag + @CPB) maintained good antibacterial capability over the tested time period. In addition, all the cements showed high injectability and interdigitating capability in cancellous bone and demonstrated augmentation effect on the cannulated pedicle screws fixation in the Sawbones model. In summary, the sustainable antibacterial capability and enhanced biomechanical properties demonstrated that Ag + ions were more suitable for the fabrication of antibacterial CPC compared to AgNPs. Also, the H-Ag + @CPB, with good injectability, high cytocompatibility, good interdigitating and biomechanical property in cancellous bone, and sustainable antibacterial effects , bears great potential for the treatments of bone infections or implant-associated infections.

研究领域: 材料科学 · 生物医学工程 · 骨科 · 生物材料
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Advanced Healthcare Materials · 2023 · IF 10

A Multifunction Hydrogel-Coating Engineered Implant for Rescuing Biofilm Infection and Boosting Osseointegration by Macrophage-Related Immunomodulation

Yao Ding,Genhua Liu,Shaopeng Liu,Xuan Li,Kun Xu,Peng Liu,Kaiyong Cai

Innovative methodologies combined with scavenging reactive oxygen species (ROS), alleviating oxidative stress damage and promoting macrophage polarization to M2 phenotype may be ideal for remodeling implant-infected bone tissue. Herein, a functionalization strategy for doping Tannic acid- d -tyrosine nanoparticles with photothermal profile into the hydrogel coating composed of konjac gum and gelatin on the surface of titanium (Ti) substrate is accurately constructed. The prepared hydrogel coating exhibits excellent properties of eliminating biofilm and killing planktonic bacteria, which is based on increasing susceptibility to bacteria by the photothermal effect, biofilm-dissipation effect of D-tyrosine, as well as the bactericidal effect of tannic acid. In addition, the modified Ti substrate has effectively alleviated proinflammatory responses by scavenging intracellular excessive ROS and guiding macrophages polarization toward M2. More interesting, conditioned medium from macrophage indicates that paracrine is conducive to osteogenic proliferation and differentiation of mesenchymal stem cells. Results from rat model of femur infection in vivo demonstrate that the modified Ti implant significantly eliminates the residual bacteria, relieves inflammation, mediates macrophage polarization, and accelerates osseointegration. Altogether, this study exhibits a new perspective for the development of advanced functional implant with great application potential in bone tissue regeneration and repair.

CAS / MDL: 1401-55-4
研究领域: 生物材料 · 生物医学工程 · 免疫学 · 骨科 · 组织工程
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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

Surface modification of titanium implants by ZIF-8@Levo/LBL coating for inhibition of bacterial-associated infection and enhancement of in vivo osseointegration

Bailong Tao,Weikang Zhao,Chuanchuan Lin,Zhang Yuan,Ye He,Lu Lu,Maowen Chen,Yao Ding,Yulu Yang,Zengzilu Xia,Kaiyong Cai

Bone implant-associated infection is one of the major concerns in orthopedics, and may even result in implant failure. To this end, we developed a strategy for the fabrication of an antibacterial coating on titanium (Ti) implants with pH-response to combat bacteria-mediated acidification of the local microenvironment. It includes three steps: first, we synthesized levofloxacin (Levo)-loaded zeolitic imidazolate framework-8 ( [email protected] ) nanoparticles; second, the nanoparticles were loaded onto the collagen-modified Ti substrates by the cathode electrophoresis deposition (EPD) method; third, gelatin (Gel) and chitosan (Chi) multilayers were spin-coated on the modified Ti substrates, since the chelating effect of Gel and Chi would reduce the hydrolysis of [email protected] for a sustained release of Levo and Zn 2+ . The fabricated samples of [email protected] /LBL promoted in vitro adhesion, proliferation, and differentiation of osteoblasts. Moreover, the [email protected] /LBL samples exhibited strong antibacterial ability against Escherichia coli and Staphylococcus aureus through hydrolysis of ZIF-8 nanoparticles, thereby creating a marginally alkaline microenvironment. Furthermore, in vivo implantation in a femur-infected rat model revealed that [email protected] /LBL implants effectively inhibited bacterial adhesion, apart from significantly improving osseointegration of the Ti implants. The study provides a promising alternative for fabricating multifunctional Ti implants with strong antibacterial capacity and enhanced bone formation for potential orthopedic application.

研究领域: 生物材料 · 骨科 · 生物医学工程 · 材料科学
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Bioactive Materials · 2022 · IF 16.874

Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

Ying Yang,Min Li,Bixia Zhou,Xulei Jiang,Dou Zhang,Hang Luo

Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.

CAS / MDL: 107-21-1 7440-55-3
研究领域: 生物材料 · 组织工程 · 骨科 · 感染性疾病 · 纳米技术 · 生物医学工程
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