Browsing by Author "Luo F."

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    Establishment of a biosafe murine model of skeletal tuberculosis using Mycobacterium smegmatis
    (2026-01-01) Jia Y.; Guo Y.; Yang Y.; Zhang J.; Zhang Z.; Qu Y.; Tan J.; Shen J.; Limjunyawong N.; Xu J.; Zhang Z.; Luo F.; Dou C.; Jia Y.; Mahidol University
    Background: Skeletal tuberculosis (TB) remains a persistent clinical and research challenge due to its chronic course, osteolytic destruction, and the limitations of existing animal models, which often require high-level biosafety containment or fail to replicate human skeletal pathology. Methods: This study developed a biosafe, accessible, and versatile murine model of skeletal TB using Mycobacterium smegmatis, a fast-growing, nonpathogenic mycobacterial species with high genomic homology to Mycobacterium tuberculosis. Three infection routes—subperiosteal calvarial injection, intratibial injection, and intracardiac inoculation—were systematically evaluated for their ability to induce localized versus disseminated bone infection under standard biosafety level (BSL)-1 conditions. Results: Subperiosteal calvarial and intratibial injection of M. smegmatis induced localized bone lesions characterized by osteolysis, sequestrum formation, granulomatous inflammation, and increased osteoclast activity. Intratibial infection additionally triggered compartment-specific immune responses, including neutrophil and macrophage expansion, transient B-cell depletion, and activation of interferon-γ+ (IFN-γ+) T cells, reflecting active immune remodeling at the infection site. Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation. Compared to intratibial infection, intracardiac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis. Conclusions: This M. smegmatis–based murine model provides a straightforward, reliable, and immunopathologically relevant platform for exploring host–pathogen dynamics, immune-driven bone destruction, and early-stage therapeutic testing in skeletal TB, all within standard BSL-1 laboratories. This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
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    LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration
    (2024-10-01) Ye P.; Yang Y.; Qu Y.; Yang W.; Tan J.; Zhang C.; Sun D.; Zhang J.; Zhao W.; Guo S.; Song L.; Hou T.; Zhang Z.; Tang Y.; Limjunyawong N.; Xu J.; Dong S.; Dou C.; Luo F.; Ye P.; Mahidol University
    This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.