Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Introduction. Infection remains as one of the major challenges of total joint surgery. One-stage irrigation, debridement and reimplantation, or two-stage revision surgery with a temporary implantation of antibiotic eluting bone cement spacer followed by reimplantation are two methods often used to treat infected patients with mixed outcomes. Like bone cement, ultra-high molecular weight polyethylene (UHMWPE) can also be used as a carrier for antibiotics. Recently, we demonstrated that vancomycin and rifampin can be delivered from UHMWPE implants at therapeutic levels to eradicate Staphylococcus aureus biofilm in a lupine animal model. There are regulatory challenges in translating these types of combination devices to clinical use. Last year, at this meeting, we presented the preliminary pre-clinical testing for a temporary UHMWPE spacer containing gentamicin sulfate as a first step towards clinical use. Since then, we carried out a survey among the Knee Society membership about their preference for spacer use in two-stage revision surgery and found that 43% prefer to use a CoCr femoral component on an all-poly cemented tibial insert, 22% prefer bone cement spacers molded in the OR, 20% prefer static bone cement spacers, and 14% prefer pre-formed bone cement spacers. We modified our implant design based on the majority's preference for a total knee system, rather than bone cement spacers, in the temporary two-stage approach. In this study, we explored the effect of gentamicin sulfate (GS) elution from UHMWPE/GS tibial inserts on bacterial colonization on CoCr surfaces. Methods. We characterized the gentamicin sulfate (GS) particles with scanning electron microscopy (SEM). We molded UHMWPE/GS powder blends and characterized the morphology using SEM and Energy Dispersive X-Ray Spectroscopy (EDS). We submerged samples of molded UHMWPE/GS in buffered phosphate solution (PBS) at 37°C and quantified the extent of GS elution into PBS with a method described by Gubernator et al. using o-phthaladehyde (OPA) [1]. Under basic conditions, OPA reacts with primary amino groups to form fluorescent complexes. Since gentamicin is the only source of such amino acids in our elution samples, the number of fluorescent complexes formed is directly proportional to the amount of gentamicin in the sample. Using this method, we could quantify gentamicin elution by measuring sample fluorescence post OPA-reaction. We used a plate reader to excite the fluorescent complexes formed in the OPA reaction and measured the resulting emission at wavelengths of 340 nm and 455 nm, respectively. We also quantified the effect of the standard cleaning protocol (heated sonication in alkaline water and alcohol) used to clean UHMWPE implants on subsequent GS elution from UHMWPE/GS samples using the OPA method. We used agar diffusion tests to characterize antibacterial properties of UHMWPE/GS samples after cleaning. For these tests, we collected eluents collected from UHMWPE/GS and gentamicin-impregnated bone cement (BC/GS) following 1, 2, 3, and 4 weeks of elution, and tested against S. aureus (ATCC 12600). We used the “daughter cells” method developed by Bechert et al. to assess anticolonizing properties of UHMWPE/GS [2,3]. We also characterized the colonization of bacteria on CoCr surfaces in the presence of GS eluting from UHMWPE/GS test samples. For this we modified a Pin-on-Disc (PoD) wear tester: An UHMWPE/GS pin and UHMWPE pin (control) articulated against an implant-finish CoCr disc with Tryptic Soy Broth containing S. Aureus as the lubricant. After 18 hrs, we rinsed the articular surfaces of the pin and disc and stamped them onto Agar gel to transfer any adherent bacteria. We incubated the Agar plate overnight such that adherent bacteria proliferated and became visible. Results. SEM characterized the GS particles as hollow spheres (Fig 1a). These formed small groups of agglomerated domains at the virgin resin boundaries of UHMWPE after molding (Fig 1b). Sulfur signature from the EDS analysis identified the agglomerated domains as GS particles (Fig 2). Elution of GS started with an initial burst and was followed by steady elution up to 12 weeks (Fig 3). Cleaning reduced the initial burst GS elution; and the elution remained unchanged after 2 days (Fig 4). The agar diffusion test showed simmilar inhibition zones for the eluents collected from UHMWPE/GS and BC/GS, suggesting that these samples yield similar antibacterial activity against S. aureus (Fig 5). UHMWPE/GS demonstrated pronounced anticolonizing properties, effectively mitigating the proliferation of S. aureus “daughter” cells. Anticolonizing activity of Palacos R+G was not significantly different when compared with UHMWPE/GS. The PoD test showed little-to-no colonization of CoCr surfaces in the presence of UHMWPE/GS pins, indicative of excellent antibacterial properties of UHMWPE/GS against S. aureus. Conclusion. SEM and EDS has allowed us to visualize domains of gentamicin sulfate particles in UHMWPE. Our OPA method has greater precision than traditional agar-well diffusion methods of measuring gentamicin concentration and showed that gentamicin sulfate-loaded UHMWPE elutes at the same rate as Palacos R+G. Pin-on-disc experiments and the daughter cell method both confirmed that these two materials have similar anticolonization abilities. We also found that using the standard cleaning protocol for UHMWPE orthopedic implants decreased the burst of gentamicin eluting from UHMWPE, but after 2 days, it had no effect compared to uncleaned UHMWPE/GS. Finally, we found that UHMWPE/GS can reduce the colonization of bacteria on CoCr. UHMWPE/GS continues to be a promising material for treating PJI. For figures, tables, or references, please contact authors directly

Aims

The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs).

Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Aims

We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement.

Objective

Mortality rates reported by the National Joint Registry for England and Wales (NJR) were higher following cemented total knee replacement (TKR) compared with uncemented procedures. The aim of this study is to examine and compare the effects of cemented and uncemented TKR on the activation of selected markers of inflammation, endothelium, and coagulation, and on the activation of selected cytokines involved in the various aspects of the systemic response following surgery.