Does an antibiotic-loaded hydrogel coating reduce early post-surgical infection after joint arthroplasty?

Background: Infection remains among the main reasons for joint prosthesis failure. Preclinical reports have suggested that antibacterial coatings of implants may prevent bacterial adhesion and biofilm formation. This study presents the results of the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating (Defensive Antibacterial Coating, DAC®) in patients undergoing hip or knee prosthesis. Methods: In this multicenter, randomized prospective study, a total of 380 patients, scheduled to undergo primary (n=270) or revision (n=110) total hip (N=298) or knee (N=82) joint replacement with a cementless or a hybrid implant, were randomly assigned, in six European orthopedic centers, to receive an implant either with the antibiotic-loaded DAC coating (treatment group) or without coating (control group). Pre- and postoperative assessment of clinical scores, wound healing, laboratory tests, and x-ray exams were performed at fixed time intervals. Results: Overall, 373 patients were available at a mean follow-up of 14.5 ± 5.5 months (range 6 to 24). On average, wound healing, laboratory and radiographic findings showed no significant difference between the two groups. Eleven early surgical site infections were observed in the control group and only one in the treatment group (6% vs. 0.6%; p=0.003). No local or systemic side effects related to the DAC hydrogel coating were observed, and no detectable interference with implant osteointegration was noted. Conclusions: The use of a fast-resorbable, antibiotic-loaded hydrogel implant coating can reduce the rate of early surgical site infections, without any detectable adverse events or side effects after hip or knee joint replacement with a cementless or hybrid implant

Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis : a multicenter randomized controlled trial

BACKGROUND: Infection is one of the main reasons for failure of orthopedic implants. Antibacterial coatings may prevent bacterial adhesion and biofilm formation, according to various preclinical studies. The aim of the present study is to report the first clinical trial on an antibiotic-loaded fast-resorbable hydrogel coating (Defensive Antibacterial Coating, DAC\uae) to prevent surgical site infection, in patients undergoing internal osteosynthesis for closed fractures. MATERIALS AND METHODS: In this multicenter randomized controlled prospective study, a total of 256 patients in five European orthopedic centers who were scheduled to receive osteosynthesis for a closed fracture, were randomly assigned to receive antibiotic-loaded DAC or to a control group (without coating). Pre- and postoperative assessment of laboratory tests, wound healing, clinical scores and X-rays were performed at fixed time intervals. RESULTS: Overall, 253 patients were available with a mean follow-up of 18.1 \ub1 4.5 months (range 12-30). On average, wound healing, clinical scores, laboratory tests and radiographic findings did not show any significant difference between the two groups. Six surgical site infections (4.6%) were observed in the control group compared to none in the treated group (P < 0.03). No local or systemic side-effects related to the DAC hydrogel product were observed and no detectable interference with bone healing was noted. CONCLUSIONS: The use of a fast-resorbable antibiotic-loaded hydrogel implant coating provides a reduced rate of post-surgical site infections after internal osteosynthesis for closed fractures, without any detectable adverse event or side-effects. LEVEL OF EVIDENCE: 2

HGF-Transgenic MSCs Can Improve the Effects of Tissue Self-Repair in a Rabbit Model of Traumatic Osteonecrosis of the Femoral Head

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is generally characterized as an irreversible disease and tends to cause permanent disability. Therefore, understanding the pathogenesis and molecular mechanisms of ONFH and developing effective therapeutic methods is critical for slowing the progress of the disease. METHODOLOGY/PRINCIPAL FINDINGS: In this study, an experimental rabbit model of early stage traumatic ONFH was established, validated, and used for an evaluation of therapy. Computed tomography (CT) and magnetic resonance (MR) imaging confirmed that this model represents clinical Association Research Circulation Osseous (ARCO) phase I or II ONFH, which was also confirmed by the presence of significant tissue damage in osseous tissue and vasculature. Pathological examination detected obvious self-repair of bone tissue up to 2 weeks after trauma, as indicated by revascularization (marked by CD105) and expression of collagen type I (Col I), osteocalcin, and proliferating cell nuclear antigen. Transplantation of hepatocyte growth factor (HGF)-transgenic mesenchymal stem cells (MSCs) 1 week after trauma promoted recovery from ONFH, as evidenced by a reversed pattern of Col I expression compared with animals receiving no therapeutic treatment, as well as increased expression of vascular endothelial growth factor. CONCLUSIONS/SIGNIFICANCE: These results indicate that the transplantation of HGF-transgenic MSCs is a promising method for the treatment for ONFH and suggest that appropriate interference therapy during the tissue self-repair stage contributes to the positive outcomes. This study also provides a model for the further study of the ONFH etiology and therapeutic interventions

Central Role of SREBP-2 in the Pathogenesis of Osteoarthritis

Background: Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action. Methodology/Principal Findings: We performed a genetic association analysis using a cohort of 1,410 Greek OA patients and healthy controls and found significant association between single nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development. Moreover, the above SNP was functionally active, as normal chondrocytes’ transfection with SREBP-2-G/C plasmid resulted in interleukin-1β and metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-$\beta$ (TGF-$\beta$) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes. To test whether TGF-$\beta$ alone can induce SREBP-2, we treated normal chondrocytes with TGF-$\beta$ and found significant upregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-$\beta$ activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo-RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13 expression levels. Conclusions/Significance: We demonstrated, for the first time, the association of SREBP-2 with OA pathogenesis and provided evidence on the molecular mechanism involved. We suggest that TGF-$\beta$ induces SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and that integrin blockage may be a potential molecular target for OA treatment

Trabecular metal - Orthopaedic applications of a novel material

Unlike conventional porous-coated materials used in orthopaedic surgery, Trabecular Metal™ (TMT) is a novel material. It is made of tantalum with three-dimensional porosity throughout its volume resembling the structure of trabecular bone. Experimental data suggest that bone ingrowth is faster and that the stability of the implant is, at least, comparable to titanium porous-coated implants. TMT has been used in several orthopaedic applications and implants made of TMT are in clinical use for joint replacement surgery and revision, treatment of avascular necrosis of the hip and spine surgery. Although excellent mid-term clinical results have been published for hip and knee replacement and revision, long-term behaviour is as yet unknown and several specific devices are still in an early stage. Based on biomechanical characteristics, experimental preclinical data and the published clinical experience, TMT appears to be a promising material for orthopaedic implants, particularly for revision surgery. © TOUCH BRIEFINGS 2011

Bone-implant interface in biofilm-associated bone and joint infections

Total hip and knee arthroplasties are considered the procedures of the twentieth century, with dramatic improvement to the overall quality of life for millions of patients around the globe. The application of fracture fixation implants and the replacement of the arthritic joints became a common practice in modern orthopedics, relieving hundreds of thousands of patients of pain and functional disability. With a share of 38 %, orthopedics and traumatology are the worldwide leading markets of implanted biomaterials, involving millions of new patients each year as an increasing trend. Commonly used implants in orthopedics are mainly employed for the fixation or reconstruction of bones and joints or their parts and adjacent soft tissues (ligaments, tendons, menisci, etc.) and are made of biocompatible metals, polymers, ceramics, hydroxyapatite, and their combinations. The first requirement of a material's biocompatibility is that, whatever the desired function, the material should not induce any adverse effects in the patient, "just as the first principle of Hippocrates was that the doctor should do no harm". © 2014 Springer-Verlag London. All rights are reserved

The socio-economic burden of musculoskeletal infections

Musculoskeletal disorders are the most common cause of severe chronic pain and physical disability affecting many millions of people. Their impact on the health related quality of life of the individual, the society and the health care systems is enormous [45]. This trend will increase dramatically over the next years as the population is ageing and the lifestyle is changing towards more mobility and recreational activities. These parameters have brought up musculoskeletal disorders as the most expensive disease category, requiring 23% of the total cost of illness treatment as the Swedish cost of illness study has indicated. The indirect costs related to morbidity and disability are the greatest in most European Union countries and in the United States, while in both the total Health Expenditures are increasing in relation with the respective gross domestic products [45]. For example, since 1965, the percentage of the United States gross domestic product spent on health care has increased from 5% to 13.4%, a figure that is expected to continue to rise to 15.9% by 2010 [75]. However, the disorders of the bone and the joints have not yet been addressed as health care priorities. The established market economies allocate less than 5% of their national spending on research related to these conditions. © 2007 Springer-Verlag Berlin Heidelberg