Efficacy of pH-Responsive Surface Functionalized Titanium Screws in Treating Implant-associated S. aureus Osteomyelitis with Biofilms Formation.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis (IASO) leads to high orthopedic implant failure rates due to the formation of Staphylococcal abscess community within the bone marrow and bacterial colonization in the osteocyte lacuno-canalicular network (OLCN). To address this, antimicrobial peptides (HHC36)-loaded titania nanotubes (NTs) are developed on titanium screws (Ti-NTs-P-A), which integrate pH-responsive polymethacrylic acid to control HHC36 release for eradicating bacteria in IASO.

Borosilicate bioactive glass synergizing low-dose antibiotic loaded implants to combat bacteria through ATP disruption and oxidative stress to sequentially achieve osseointegration.

Bone infection is a catastrophe in clinical orthopedics. Despite being the standard therapy for osteomyelitis, antibiotic-loaded polymethyl methacrylate (PMMA) cement has low efficiency against bacteria in biofilms. Furthermore, high-dose antibiotic-loaded implants carry risks of bacterial resistance, tissue toxicity, and impairment of local tissue healing.

Vaccines: Do they have a role in orthopedic trauma?

Although vaccines have been hailed as one of the greatest advances in medicine based on their unparalleled cost-effectiveness in eradicating life-threatening infectious diseases, their role in orthopedic trauma-related infections is unclear. This is largely because vaccines are primarily made against pathogens that cause communicable diseases rather than opportunistic infections secondary to trauma, and most successful vaccines are against viruses rather than biofilm forming bacteria. Nonetheless, the tremendous costs to patients and healthcare systems warrant orthopedic trauma vaccine research, which has been a focal topic in recent international consensus meetings on musculoskeletal infection.

Exploratory Investigation of Zinc-Modified Borosilicate Bioactive Glass: A New Methodology for Its Biocompatibility, Immunoregulation, and Pro-Angiogenic Property Evaluation.

The assessment of biodegradable materials, such as bioactive glass, under the existing ISO 10993 standard test methods poses a significant challenge due to potential cell viability impairment caused by the accumulation of degraded products in a static environment. Therefore, innovative methodologies are urgently needed to tailor the unique biodegradation characteristics of these materials, providing more precise and scientific insights into biosafety and efficacy verification. Motivation by its bidirectional regulation of angiogenesis and immunity, zinc (Zn) was incorporated into sol-gel-derived borosilicate bioactive glasses (SBSGs) to fabricate Zn-incorporated borosilicate bioactive glasses (SBSG-Zn) to complement the tissue repair capabilities of bioactive glasses.

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and FeO magnetic nanoparticle scaffold on implant-associated bone infection.

Implant-associated () osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (FeO) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities.

A semi-automated cell tracking protocol for quantitative analyses of neutrophil swarming to sterile and S. aureus contaminated bone implants in a mouse femur model.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S.

A semi-automated cell tracking protocol for quantitative analyses of neutrophil swarming to sterile and contaminated bone implants in a mouse femur model.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize fluorescent on a contaminated transfemoral implant and host cells in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy.

2023 International Consensus Meeting on musculoskeletal infection: Summary from the treatment workgroup and consensus on treatment in preclinical models.

In vitro and in vivo studies are critical for the preclinical efficacy assessment of novel therapies targeting musculoskeletal infections (MSKI). Many preclinical models have been developed and applied as a prelude to evaluating safety and efficacy in human clinical trials. In performing these studies, there is both a requirement for a robust assessment of efficacy, as well as a parallel responsibility to consider the burden on experimental animals used in such studies.

Longitudinal intravital imaging of the bone marrow for analysis of the race for the surface in a murine osteomyelitis model.

Critical knowledge gaps of orthopedic infections pertain to bacterial colonization. The established dogma termed the Race for the Surface posits that contaminating bacteria compete with host cells for the implant post-op, which remains unproven without real-time in vivo evidence. Thus, we modified the murine longitudinal intravital imaging of the bone marrow (LIMB) system to allow real-time quantification of green fluorescent protein (GFP+) host cells and enhanced cyan fluorescent protein (ECFP+) or red fluorescent protein (RFP+) methicillin-resistant Staphylococcus aureus (MRSA) proximal to a transfemoral implant.

Evidence of Bisphosphonate-Conjugated Sitafloxacin Eradication of Established Methicillin-Resistant S. aureus Infection with Osseointegration in Murine Models of Implant-Associated Osteomyelitis.

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve "target-and-release" drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux).

Reduced angiogenesis and delayed endochondral ossification in CD163 mice highlights a role of M2 macrophages during bone fracture repair.

While recent studies showed that macrophages are critical for bone fracture healing, and lack of M2 macrophages have been implicated in models of delayed union, functional roles for specific M2 receptors have yet to be defined. Moreover, the M2 scavenger receptor CD163 has been identified as a target to inhibit sepsis following implant-associated osteomyelitis, but potential adverse effects on bone healing during blockage therapy have yet to be explored. Thus, we investigated fracture healing in C57BL/6 versus CD163 mice using a well-established closed, stabilized, mid-diaphyseal femur fracture model.

Efficacy of Bisphosphonate-Conjugated Sitafloxacin in a Murine Model of Osteomyelitis: Evidence of "Target & Release" Kinetics and Killing of Bacteria Within Canaliculi.

infection of bone is difficult to eradicate due to its ability to colonize the osteocyte-lacuno-canalicular network (OLCN), rendering it resistant to standard-of-care (SOC) antibiotics. To overcome this, we proposed two bone-targeted bisphosphonate-conjugated antibiotics (BCA): bisphosphonate-conjugated sitafloxacin (BCS) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS). Initial studies demonstrated that the BCA kills .

Relapsed boyhood tibia polymicrobial osteomyelitis linked to dermatophytosis: a case report.

Background: Relapsed childhood polymicrobial osteomyelitis associated with dermatophytosis has not been reported in the literature.

Case Presentation: Here we report on a case of a 45-year-old man who had left tibial osteomyelitis for 29 years, accompanied by skin fungal infection of the ipsilateral heel for 20 years, and underwent a second operation due to recurrence of polymicrobial infection 6 years ago. The patient had a history of injury from a rusty object, which penetrated the anterior skin of the left tibia middle segment causing subsequent bone infection, but was asymptomatic after receiving treatments in 1983.

Distinct expression trend of signature antigens of Staphylococcus aureus osteomyelitis correlated with clinical outcomes.

The major limitations of clinical outcome predictions of osteomyelitis mediated by Staphylococcus aureus (S. aureus) are not specific and definitive. To this end, current studies aim to investigate host immune responses of trend changes of the iron-regulated surface determinant (Isd) of IsdA, IsdB, IsdH, cell wall-modifying proteins of amidase (Amd) and glucosaminidase (Gmd), and secreted virulence factor of chemotaxis inhibitory protein S.

Therapeutic Effectiveness of Percutaneous Endoscopic Spinal Surgery for Intraspinal Cement Leakage Following Percutaneous Vertebroplasty: An Early Clinical Study of 12 Cases.

Background: Intraspinal cement leakage is a catastrophic complication of percutaneous vertebroplasty (PVP). Percutaneous endoscopic spinal surgery (PESS) for intraspinal cement leakage has rarely been reported.

Objectives: To evaluate the therapeutic effectiveness of PESS for intraspinal cement leakage following PVP.

Erratum to pathogen identification in 84 patients with post-traumatic osteomyelitis after limb fractures.

This corrects the article DOI: 10.21037/apm.2020.

The combinations of multiple factors to improve the diagnostic sensitivity and specificity after artificial joint infection.

Objective: To discuss the sensitivity and specificity of the combinations of multiple factors that work on bone infection after artificial joint, and provide evidence-based medical basis for the early diagnosis of infection after artificial joint.

Methods: A retrospective review was conducted on 35 patients diagnosed with periprosthetic joint infections (PJI) or aseptic loosening (AL) who both received revision operation from January 2011 to January 2015. Analyzing and comparing their epidemiology indexes and expounded a series of auxiliary examinations corresponding positive diagnosis ratio.

Pathogen identification in 84 Patients with post-traumatic osteomyelitis after limb fractures.

Background: Chronic osteomyelitis is a serious complication of orthopedic trauma. Residual bacteria after incomplete debridement and/or bacterial colonization, bacterial biofilm formation, and generation of antibiotic-resistant bacterial strains in the microtubule system of compact bones due to irrational use of antibiotics often make the condition more prolonged, recurrent, and refractory. The passive immunotherapy targeting the protein components of bacteria has become an area of intense research interest, for which identifying the bacterial isolates in different areas at different time points remains a key step.

Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF.

Human amniotic mesenchymal stem cells (hAMSCs) are multiple potent progenitor cells (MPCs) that can differentiate into different lineages (osteogenic, chondrogenic, and adipogenic cells) and have a favorable capacity for angiogenesis. Schnurri-3 (Shn3) is a large zinc finger protein related to Drosophila Shn, which is a critical mediator of postnatal bone formation. Bone morphogenetic protein 9 (BMP9), one of the most potent osteogenic BMPs, can strongly upregulate various osteogenesis- and angiogenesis-related factors in MSCs.

Enhancement of in vitro proliferation and bioactivity of human anterior cruciate ligament fibroblasts using an in situ tissue isolation method and basic fibroblast growth factor culture conditions: A pilot analysis.

Background: Previous studies have reported poor proliferation and bioactivity of human anterior cruciate ligament fibroblasts (hACLFs) after injury. As hACLFs are one of the most significant and indispensable source of seed cells in constructing tissue-engineered ligament, enhancing hACLF proliferation would offer favorable cellular-biological ability and induce the extracellular matrix secretion of hACLFs after loading on multiple types of scaffolds. Enhancing the bioactivity of hACLFs would improve tissue repair and functional recovery after tissue-engineered ligament transplantation.

All-arthroscopic release for treating severe knee extension contractures could improve the knee range of motion and the mid-term functional outcomes.

Purpose: To evaluate the safety, feasibility, and effectiveness of an all-arthroscopic technique for the intra- and extraarticular release of severe knee extension contractures.

Methods: From 2012 to 2016, 25 patients with severe knee extension contractures (less than 45° range of flexion) were treated with an all-arthroscopic release technique. The patients underwent intra- and extraarticular arthroscopic release and arthroscopic-assisted mini-incision quadriceps plasty.