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In Vivo Mouse Model of Spinal Implant Infection
Published on: June 23, 2020
In situ sprayed hydrogels containing resiquimod-loaded liposomes reduce chronic osteomyelitis recurrence by
Liangjie Tian1, Zilin Tan2, Yusheng Yang1
1Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province 510515, China.
Abstract:
At present, surgical debridement and systematic administration of antibiotics represent the mainstay of treatment for chronic osteomyelitis. However, it is now understood that Staphylococcus aureus (S. aureus) can survive within excessively polarized M2 macrophages and evade antibiotics, accounting for the high recurrence of chronic osteomyelitis. Effective treatments for intracellular infection have rarely been reported. Herein, we designed an in situ sprayed liposomes hydrogels spray with macrophage-targeted effects and the ability to reverse polarization and eradicate intracellular bacteria to reduce the recurrence of osteomyelitis. Resiquimod (R848)-loaded and phosphatidylserine (PS)-coating nanoliposomes were introduced into fibrinogen and thrombin to form the PSL-R848@Fibrin spray. Characterization and phagocytosis experiments were performed to confirm the successful preparation of the PSL-R848@Fibrin spray. Meanwhile, in vitro cell experiments validated its ability to eliminate intracellular S. aureus by reprogramming macrophages from the M2 to the M1 phenotype. Additionally, we established a chronic osteomyelitis rat model to simulate the treatment and recurrence process. Histological analysis demonstrated a significant increase in M1 macrophages and the elimination of intracellular bacteria. Imaging revealed a significant decrease in osteomyelitis recurrence. Overall, the liposome hydrogels could target macrophages to promote antibacterial properties against intracellular infection and reduce the recurrence of chronic osteomyelitis, providing the foothold for improving the outcomes of this patient population. STATEMENT OF SIGNIFICANCE: Chronic osteomyelitis remains a high recurrence although undergoing traditional treatment of debridement and antibiotics. S. aureus can survive within the excessively polarized M2 macrophages to evade the effects of antibiotics. However, few studies have sought to investigate effective intracellular bacteria eradication. Herein, we designed a macrophage-targeted R848-containing liposomes fibrin hydrogels spray (PSL-R848@Fibrin) that can reprogram polarization of macrophages and eradicate intracellular bacteria for osteomyelitis treatment. With great properties of rapid gelation, strong adhesion, high flexibility and fit-to-shape capacity, the facile-operated immunotherapeutic in-situ-spray fibrin hydrogels exhibited huge promise of reversing polarization and fighting intracellular infections. Importantly, we revealed a hitherto undocumented treatment strategy for reducing the recurrence of chronic osteomyelitis and potentially improving the prognosis of chronic osteomyelitis patients.
Insights
This study introduces a novel liposome hydrogel spray to combat chronic osteomyelitis by targeting Staphylococcus aureus within macrophages. The spray reprograms immune cells, eradicates intracellular bacteria, and significantly reduces osteomyelitis recurrence.
Area of Science:
- Biomaterials Science
- Immunology
- Infectious Diseases
Background:
- Chronic osteomyelitis often recurs despite debridement and antibiotics due to Staphylococcus aureus evading treatment within M2 macrophages.
- Effective strategies for eradicating intracellular bacteria in chronic osteomyelitis are limited.
- Targeting macrophage polarization is a potential therapeutic avenue for persistent infections.
Purpose of the Study:
- To design and evaluate an in situ sprayed liposome hydrogel with macrophage-targeting capabilities.
- To assess the hydrogel's ability to reverse M2 macrophage polarization and eliminate intracellular S. aureus.
- To investigate the efficacy of the hydrogel in reducing chronic osteomyelitis recurrence in a rat model.
Main Methods:
- Development of a phosphatidylserine (PS)-coated, Resiquimod (R848)-loaded nanoliposome fibrin hydrogel spray (PSL-R848@Fibrin).
- In vitro characterization, phagocytosis assays, and macrophage reprogramming experiments.
- Establishment of a chronic osteomyelitis rat model for in vivo efficacy assessment.
Main Results:
- Successful preparation and characterization of the PSL-R848@Fibrin spray.
- In vitro validation of intracellular S. aureus eradication by reprogramming M2 macrophages to M1 phenotype.
- In vivo studies showed increased M1 macrophages, elimination of intracellular bacteria, and significantly reduced osteomyelitis recurrence.
Conclusions:
- The developed liposome hydrogel spray effectively targets macrophages to combat intracellular S. aureus infections.
- This immunotherapeutic approach shows promise in reducing chronic osteomyelitis recurrence by reprogramming macrophages.
- The study presents a novel strategy for improving outcomes in chronic osteomyelitis patients.
