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Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first‐line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug‐resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone–implant interface. [ABSTRACT FROM AUTHOR]

Infection is a common cause of impaired fracture healing. In the clinical setting, definitive fracture treatment and infection are often treated separately and sequentially, by different clinical specialties. The ability to treat infection while promoting fracture healing will greatly reduce the cost, number of procedures, and patient morbidity associated with infected fractures. In order to develop new therapies, scientists and engineers must understand the clinical need, current standards of care, pathologic effects of infection on fractures, available preclinical models, and novel technologies. One of the main causes of poor fracture healing is infection; unfortunately, bone regeneration and infection research are typically approached independently and viewed as two separate disciplines. Here, we aim to bring these two groups together in an educational workshop to promote research into the basic and translational science that will address the clinical challenge of delayed fracture healing due to infection. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patie[Q2]nt well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly l[Q3]ower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. Statement of clinical significance: Infection and nonunion are each feared outcomes in fracture care, and infection is a significant driver of nonunion. The impact of nonunions on patient well‐being is substantial. Outcome data suggests a long bone nonunion is as impactful on health‐related quality of life measures as a diagnosis of type 1 diabetes and fracture‐related infection has been shown to significantly lower a patient's quality of life for over 4 years. Although they frequently are associated with one another, the treatment approaches for infections and nonunions are not always complimentary and cannot be performed simultaneously without accepting tradeoffs. Furthermore, different clinical specialties are often required to address the problem, the orthopedic surgeon treating the fracture and an infectious disease specialist addressing the sources of infection. A sequential approach that optimizes treatment parameters requires more time, more surgeries, and thus confers increased morbidity to the patient. The ability to solve fracture healing and infection clearance simultaneously in a contaminated defect would benefit both the patient and the health care system. [ABSTRACT FROM AUTHOR]

C‐C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant‐associated infections (OIAI), but whether CCR2‐mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic‐grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2‐deficient mice. In vivo bioluminescent signals significantly increased in CCR2‐deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony‐forming unit enumeration. S. aureus γ‐hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ‐hemolysin‐deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ‐hemolysin virulence. Although CCR2‐deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2‐deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus and Streptococcus agalactiae (Group B streptococcus, GBS) are common causes of deep musculoskeletal infections (MSKI) and result in significant patient morbidity and cost to the healthcare system. One of the major challenges with MSKI is the lack of faithful diagnostics to correctly identify the primary pathogen, as standard culture‐based assays are prone to false positives in the case of polymicrobial infections, and false negatives due to limitations in sample acquisition and antibiotic use before presentation. To improve upon our current diagnostic methods for MSKI, we developed a multiplex immunoassay for antigen‐specific IgGs in serum (Luminex), and medium enriched for newly synthesized antibodies (MENSA) for anti‐S. aureus and GBS generated from cultured peripheral blood mononuclear cells (PBMCs) of orthopedic infection patients undergoing surgical treatment. Samples were obtained from 110 MSKI patients: 80 diabetic foot ulcer, 21 periprosthetic joint infection, 5 septic arthritis, 2 spine, 1 hand, and 1 fracture‐related infection (FRI). Anti‐S. aureus and anti‐GBS antibody titers were compared to culture results to assess their concordance in identifying the pathogens. Immunoassay, particularly MENSA, showed high diagnostic potential for monomicrobial S. aureus and GBS orthopedic infections (AUC > 0.95). MENSA also demonstrated diagnostic potential for GBS polymicrobial orthopedic infection and for GBS DFU (AUC > 0.83 for both). Serum showed high diagnostic potential for S. aureus PJI (AUC > 0.95). Taken together, these findings support the development of species‐specific immunoassays for the identification of causal pathogens in active MSKI, especially in conjunction with standard culture. [ABSTRACT FROM AUTHOR]