Hybrid Outer Membrane Vesicles with Genetically Engineering for Treatment of Implant-Associated Infections and Relapse Prevention Through Host Immunomodulation

被引：0
作者：
Wang, Zhichao [1 ]
Li, Mingfei [1 ,2 ]
Li, Wenshuai [2 ]
He, Liuliang [1 ]
Wang, Long [1 ]
Cai, Kehan [1 ]
Zhao, Xiao [3 ]
Chen, Yazhou [2 ]
Li, Daifeng [1 ]
机构：
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Orthoped, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Henan Inst Adv Technol, Affiliated Hosp 1, Med Printing Ctr 3D, Zhengzhou 450052, Peoples R China
[3] Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China
来源：
ADVANCED SCIENCE | 2025年
基金：
中国国家自然科学基金;
关键词：
bacterial outer membrane vesicles; bone marrow targeting; immunomodulation; implant-associated infections; relapse prevention; BONE-MARROW; T-CELLS; MACROPHAGES; ACTIVATION;
D O I：
10.1002/advs.202415379
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Implant-associated infections (IAIs) are refractory to elimination, and the local immunosuppressive microenvironment (IME) exacerbates therapeutic difficulties, ultimately causing persistence and relapse. Therefore, exploring immunostrengthening treatments holds great promise for reversing IME and thoroughly eradicating chronic or repetitive infections. Bacterial outer membrane vesicles (OMVs) have emerged as potential immunostimulatory candidates; however, they lack active targeting capabilities and cause non-specific inflammatory side effects. In this study, bone marrow-derived mesenchymal stem cells (BMSCs) are genetically engineered to overexpress CXCR4 and isolated cell membranes (mBMSCCXCR4) for hybridization with OMVs derived from Escherichia coli (E. coli) to produce nanovesicles (mBMSCCXCR4@OMV). The resulting mBMSCCXCR4@OMV nanovesicles demonstrate excellent bone marrow targeting capability and are effectively taken up by bone marrow-derived macrophages, triggering the efficient transition to pro-inflammatory M1 status through TLR/NF-kappa B pathway. This alteration promotes innate bactericidal capacity and antigen presentation. Subsequent activation of T and B cells and inhibition of myeloid-derived suppressor cells (MDSCs) facilitated in vivo adaptive immunity in mouse models. Additionally, mBMSCCXCR4@OMV boosted memory B cell and bacteria-specific antibody responses. Together, these data highlight the potential of mBMSCCXCR4@OMV to eradicate complicated IAIs and provide whole-stage protection against postsurgical relapse, thus marking a significant immunotherapeutic advancement in the post-antibiotic era.
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页数：16
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