Osteomyelitis

Osteomyelitis remains a global challenge in the field of orthopedics. Even after standard debridement and antibiotic-assisted treatment, the long-term recurrence rate remains at 20%-30%. Given the dynamic changes in immune responses and defense mechanisms during bone infection, as well as the complex "race for the surface" involving bacterial adhesion and host cells (macrophages and tissue cells) on implant surfaces, biomaterials with immunomodulatory functions have attracted considerable attention. Macrophages, as crucial components of the immune system, participate in the inflammatory regulation and tissue remodeling of bone infections through highly plastic polarization mechanisms after bacterial invasion. The different microenvironmental characteristics and therapeutic needs at different stages of bone infection highlight the promising applications of biomaterials capable of macrophage polarization remodeling and sequential regulation. In this review, we provide a detailed discussion of the complex immune regulatory patterns in the bone infection microenvironment and the critical functions of macrophage polarization. We then explore how implant surface properties influence bacterial adhesion and macrophage function, highlighting the importance of achieving precise and dynamic regulation of macrophage polarization based on the Race for the Surface theory. Furthermore, we focus on recent advances, potential challenges, and opportunities in biomaterial-mediated macrophage polarization remodeling and sequential modulation strategies across different stages of osteomyelitis, aiming to offer insights that may accelerate the clinical translation of novel biomaterial-based macrophage immunotherapies.

Non-antibiotic strategies are desperately needed to treat post-traumatic osteomyelitis (PTO) due to the emergence of superbugs, complex inflammatory microenvironments, and greatly enriched biofilms. Previously, growing evidence indicated that quorum sensing (QS), a chemical communication signal among bacterial cells, can accelerate resistance under evolutionary pressure. This study aims to develop a medical dressing to treat PTO by inhibiting QS and regulating the inflammatory microenvironment, which includes severe oxidative stress and acid abscesses, through a reactive oxygen species (ROS)-responsive bond between N1- (4-borobenzoyl)-N3-(4-borobenzoyl)-the N1, the N1, N3, N3-tetramethylpropane-1,3-diamine (TSPBA) and polyvinyl alcohol (PVA), and the amino side chain of hyperbranched polylysine (HBPL). Physically enclosed QS inhibitors subsequently exerted the antibacterial effects. This hydrogel can scavenge hydrogen peroxide (H2O2), superoxide anion free radical (·O2 -), hydroxyl radicals (·OH) and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH) to reduce oxidative stress and inhibit "bacteria-to-bacteria communication", thus clearing planktonic bacteria and biofilms, accelerating bacterial plasmolysis, reducing bacterial virulence and interfering with membrane transport. After in vivo treatment with hydrogel, nearly all bacteria are eliminated, inflammation is effectively inhibited, and osteogenesis and bone repair are promoted to facilitate recovery from PTO. The work demonstrates the clinical translational potential of the hydrogel in the treatment of drug-resistant bacteria induced PTO.

Staphylococcus aureus, traditionally viewed as an extracellular pathogen, is increasingly recognized for its ability to persist intracellularly, particularly within macrophages. This intracellular lifestyle is central to osteomyelitis, a chronic bone infection characterized by persistent inflammation, bone destruction, and impaired repair. Within bone, S. aureus exploits macrophage plasticity by driving a shift from pro-inflammatory, bactericidal M1-like states to anti-inflammatory, tissue-reparative M2-like phenotypes. This polarization suppresses immune clearance and promotes an environment conducive to bacterial survival and dissemination. Additional strategies - including biofilm formation, small colony variants, and inhibition of phagolysosomal killing - further enhance persistence and immune evasion. While these mechanisms are well studied in extracellular infections, their role in intracellular survival is increasingly evident. This review synthesizes emerging insights into how S. aureus manipulates macrophage function to establish chronic bone infection and highlights therapeutic opportunities targeting macrophage polarization to improve immune-mediated clearance and bone repair in osteomyelitis.

BackgroundNative vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited.MethodsWe conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model.ResultsAmong 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999-2004 to 2020-2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18-3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17-2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37-0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43-0.90) were associated with lower failure.ConclusionsThis large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.