Local Delivery of Exosomes and Antibiotics in Hydroxyapatite-Based Nanocement for Osteomyelitis Management.

IF 4 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2024-10-29 DOI:10.1021/acsinfecdis.4c00721

Sneha Gupta, Irfan Qayoom, Ayushi Mairal, Sneha Singh, Ashok Kumar

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引用次数: 0

Abstract

The management of bone and joint infections is a formidable challenge in orthopedics and poses a global health concern. While clinical management emphasizes infection prevention and complete eradication, an effective strategy for stabilizing skeletal tissue with adequate soft tissue coverage remains limited. In this study, we have employed a novel approach of using the local delivery of exosomes and antibiotics (rifampicin) using a hydroxyapatite-based nanocement carrier to manage the residual space created during debridement effectively. Additionally, we synthesized a periosteum-guiding antioxidant herbal membrane to leverage the inherent periosteum regeneration capability of the bone, facilitating bone callus repair and natural healing. The synthesized scaffolds were biocompatible and demonstrated potent antibacterial activity in vitro. When evaluated in vivo in the Staphylococcus aureus-induced rat tibial osteomyelitis model, the released drugs successfully cleared the residual bacteria and the released exosome promoted bone healing, resulting in 3-fold increase in bone volume as analyzed via micro-CT analysis. Immunofluorescence staining of periosteum-specific markers also indicated the complete formation of periosteal layers, thus highlighting the complete bone repair.

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羟基磷灰石纳米水泥中外泌体和抗生素的局部输送用于骨髓炎治疗

骨与关节感染的治疗是骨科领域的一项艰巨挑战，也是一个全球性的健康问题。虽然临床管理强调预防感染和彻底根除感染，但稳定骨骼组织并充分覆盖软组织的有效策略仍然有限。在本研究中，我们采用了一种新方法，即利用羟基磷灰石纳米水泥载体局部输送外泌体和抗生素（利福平），以有效管理清创过程中产生的残余空间。此外，我们还合成了骨膜引导抗氧化草本膜，以利用骨固有的骨膜再生能力，促进骨茧修复和自然愈合。合成的支架具有生物相容性，并在体外表现出强大的抗菌活性。在金黄色葡萄球菌诱导的大鼠胫骨骨髓炎模型中进行体内评估时，释放的药物成功清除了残余细菌，释放的外泌体促进了骨愈合，通过显微 CT 分析，骨体积增加了 3 倍。骨膜特异性标记物的免疫荧光染色也表明骨膜层完全形成，从而突出了骨修复的完整性。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.