Restoring implant fixation strength in osteoporotic bone with a hydrogel locally delivering zoledronic acid and bone morphogenetic protein 2. A longitudinal in vivo microCT study in rats.

Osteoporosis poses a major public health challenge, and it is characterized by low bone mass, deterioration of the microarchitecture of bone tissue, causing a consequent increase in bone fragility and susceptibility to fractures and complicating bone fixation, particularly screw implantation. In the present study, our aim was to improve implant stability in osteoporotic bone using a thermoresponsive hyaluronan hydrogel (HA-pNIPAM) to locally deliver the bisphosphonate zoledronic acid (ZOL) to prevent bone resorption and bone morphogenetic protein 2 (BMP2) to induce bone formation. Adult female Wistar rats (n = 36) were divided into 2 treatment groups: one group of SHAM-operated animals and another group that received an ovariectomy (OVX) to induce an osteoporotic state. All animals received a polyetheretherketone (PEEK) screw in the proximal tibia. In addition, subgroups of SHAM or OVX animals received either the HA-pNIPAM hydrogel without or with ZOL/BMP2, placed into the defect site prior to screw implantation. Periprosthetic bone and implant fixation were monitored using longitudinal in vivo microCT scanning post-operatively and at 3, 6, 9, 14, 20 and 28 days. Histological assessment was performed post-mortem. Our data showed that pure hydrogel has no impact of implant fixation The ZOL/BMP2-hydrogel significantly increased bone-implant contact and peri-implant bone fraction, primarily through reduced resorption. STATEMENT OF CLINICAL SIGNIFICANCE: Local delivery of ZOL and BMP2 using a biocompatible hydrogel improved implant stability in osteoporotic bone. This approach could constitute a potent alternative to systemic drug administration and may be useful in avoiding implant loosening in clinical settings.

Mechanical assessment of two hybrid plate designs for pancarpal canine arthrodesis under cyclic loading.

Pancarpal canine arthrodesis (PCA) sets immobilization of all three carpal joints via dorsal plating to result in bony fusion. Whereas the first version of the plate uses a round hole (RH) for the radiocarpal (RC) screw region, its modification into an oval hole (OH) in a later version improves versatility in surgical application. The aim of this study was to mechanically investigate the fatigue life of the PCA plate types implementing these two features-PCA-RH and PCA-OH. Ten PCA-RH and 20 PCA-OH stainless steel (316LVM) plates were assigned to three study groups (n = 10). All plates were pre-bent at 20° and fixed to a canine forelimb model with simulated radius, RC bone and third metacarpal bone. The OH plates were fixed with an RC screw inserted either most proximal (OH-P) or most distal (OH-D). All specimens were cyclically tested at 8 Hz under 320 N loading until failure. Fatigue life outcome measures were cycles to failure and failure mode. Cycles to failure were higher for RH plate fixation (695,264 ± 344,023) versus both OH-P (447,900 ± 176,208) and OH-D (391,822 ± 165,116) plate configurations, being significantly different between RH and OH-D, p = 0.03. No significant difference was detected between OH-P and OH-D configurations, p = 0.09. Despite potential surgical advantages, the shorter fatigue life of the PCA-OH plate design may mitigate its benefits compared to the plate design with a round radiocarpal screw hole. Moreover, the failure risk of plates with an oval hole is increased regardless from the screw position in this hole. Based on these findings, the PCA plate with the current oval radiocarpal screw hole configuration cannot be recommended for clinical use.

Local bone quality measure and construct failure prediction: a biomechanical study on distal femur fractures.

INTRODUCTION: The aim of this investigation was to better understand the differences in local bone quality at the distal femur and their correlation with biomechanical construct failure, with the intention to identify regions of importance to optimize implant anchorage. MATERIALS AND METHODS: Seven fresh-frozen female femurs underwent high-resolution peripheral quantitative computed tomography (HR-pQCT) to determine bone mineral density (BMD) within three different regions of interest (distal, intermedium, and proximal) at the distal femur. In addition, local bone quality was assessed by measuring the peak torque necessary to break out the trabecular bone along each separate hole of a locking compression plate (LCP) during its instrumentation. Finally, biomechanical testing was performed using cyclic axial loading until failure in an AO/OTA 33 A3 fracture model. RESULTS: Local BMD was highest in the distal region. This was confirmed by the measurement of local bone quality using DensiProbe™. The most distal holes represented locations with the highest breakaway torque resistance, with the holes on the posterior side of the plate indicating higher values than those on its anterior side. We demonstrated strong correlation between the cycles to failure and local bone strength (measured with DensiProbe™) in the most distal posterior screw hole, having the highest peak torque. CONCLUSION: The local bone quality at the distal femur indicates that in plated distal femur fractures the distal posterior screw holes seem to be the key ones and should be occupied. Measurement of the local bone strength with DensiProbe™ is one possibility to determine the risk of construct failure, therefore, thresholds need to be defined.

Titanium Wear Particles Exacerbate S. epidermidis-Induced Implant-Related Osteolysis and Decrease Efficacy of Antibiotic Therapy.

Total joint arthroplasty (TJA) surgeries are common orthopedic procedures, but bacterial infection remains a concern. The aim of this study was to assess interactions between wear particles (WPs) and immune cells in vitro and to investigate if WPs affect the severity, or response to antibiotic therapy, of a Staphylococcus epidermidis orthopedic device-related infection (ODRI) in a rodent model. Biofilms grown on WPs were challenged with rifampin and cefazolin (100 µg/mL) to determine antibiotic efficacy. Neutrophils or peripheral blood mononuclear cells (PBMCs) were incubated with or without S. epidermidis and WPs, and myeloperoxidase (MPO) and cytokine release were analyzed, respectively. In the ODRI rodent model, rats (n = 36) had a sterile or S. epidermidis-inoculated screw implanted in the presence or absence of WPs, and a subgroup was treated with antibiotics. Bone changes were monitored using microCT scanning. The presence of WPs decreased antibiotic efficacy against biofilm-resident bacteria and promoted MPO and pro-inflammatory cytokine production in vitro. WPs exacerbated osteolytic responses to S. epidermidis infection and markedly reduced antibiotic efficacy in vivo. Overall, this work shows that the presence of titanium WPs reduces antibiotic efficacy in vitro and in vivo, induces proinflammatory cytokine release, and exacerbates S. epidermidis-induced osteolysis.

Mechanical Evaluation of Two Hybrid Locking Plate Designs for Canine Pancarpal Arthrodesis.

Hybrid locking pancarpal arthrodesis plates were designed with either a round (RH) or an oval (OH) radiocarpal hole, the latter allowing varied screw positioning. Due to concerns about potential decreased structural properties of the OH design, our aim was to compare the mechanical behavior of the contrasting plates using combined finite element analysis (FEA) and mechanical testing. Pancarpal arthrodesis plates with RH or OH design were assigned to three fixation techniques (n = 6), prebent at 20°, and fixed to canine forelimb models with simulated radius and radiocarpal and 3rd metacarpal bones. OH plates were instrumented with a radiocarpal screw inserted either most proximal (OH-P) or most distal (OH-D). Specimens were axially loaded to 300 N over 10 ramped cycles at 0.5 Hz. Plate strains were measured with strain gauges placed at areas of highest deformations as predicted by FEA under identical loading conditions. FEA predicted the highest strains (µm/m) adjacent to the radiocarpal hole (2,500 [RH], 2,900 [OH-P/OH-D]) and plate bending point (2,250 [RH], 1,900 [OH-P/OH-D]). Experimentally, peak radiocarpal hole strains were not influenced by the OH screw position (3,329 ± 443 [OH-P], 3,222 ± 467 [OH-D]; P = 0.550) but were significantly higher compared to the RH design (2,123 ± 154; P < 0.001). Peak strains at the bending point were significantly lower for OH-P (1,792 ± 174) and OH-D (1,806 ± 194) versus RH configurations (2,158 ± 114) (P ≤ 0.006). OH plates demonstrated highest peak strains next to the radiocarpal hole and were associated with more heterogenous plate strain distribution. Structural weakening associated with radiocarpal OH plate design could result in decreased fixation strength and increased risk of plate fatigue failure.

Impact of low bone mass and antiresorptive therapy on antibiotic efficacy in a rat model of orthopedic device-related infection.

A significant proportion of orthopedic devices are implanted in osteoporotic patients, but it is currently unclear how estrogen deficiency and/or exposure to antiresorptive bisphosphonates (BPs) influence orthopedic device-related infection (ODRI), or response to therapy. The aim of this study is to characterize the bone changes resulting from Staphylococcus epidermidis infection in a rodent ODRI model and to determine if ovariectomy (OVX) or BP treatment influences the infection or the success of antibiotic therapy. A sterile or S. epidermidis-contaminated screw was implanted into the proximal tibia of skeletally mature female Wistar rats (n = 6-9 per group). Bone changes were monitored over 28 days using in vivo micro-computed tomography scanning. OVX was performed 12 weeks before screw implantation. The BP zoledronic acid (ZOL) was administered 4 days before screw insertion. A combination antibiotic regimen (rifampin plus cefazolin) was administered from Days 7-21. In skeletally healthy animals, S. epidermidis induced marked changes in bone, with peak osteolysis occurring at Day 9 and woven bone deposition and periosteal mineralization from Day 14 onwards. Antibiotic therapy cleared the infection in the majority of animals (2/9 infected) but did not affect bone responses. OVX did not affect the pattern of infection-induced changes in bone, nor bacterial load, but reduced antibiotic efficacy (5/9 infected). ZOL treatment did not protect from osteolysis in OVX animals, or further affect antibiotic efficacy (5/9 infected) but did significantly increase the bacterial load. This study suggests that both BPs and OVX can influence host responses to bone infections involving S. epidermidis.

Longitudinal time-lapse in vivo micro-CT reveals differential patterns of peri-implant bone changes after subclinical bacterial infection in a rat model.

Subclinical infection associated with orthopedic devices can be challenging to diagnose. The goal of this study was to evaluate longitudinal, microcomputed tomography (microCT) imaging in a rat model of subclinical orthopedic device-related infection caused by Staphylococcus epidermidis and four different Cutibacterium (previously Propionibacterium) acnes strains, and compare outcomes with non-inoculated and historical S. aureus-inoculated controls. Sterile screws or screws colonized with bacteria were placed in the tibia of 38 adult Wistar rats [n = 6 sterile screws; n = 6 S. epidermidis-colonized screws; n = 26 C. acnes-colonized screws (covering all three main subspecies)]. Regular microCT scans were taken over 28 days and processed for quantitative time-lapse imaging with dynamic histomorphometry. At euthanasia, tissues were processed for semiquantitative histopathology or quantitative bacteriology. All rats receiving sterile screws were culture-negative at euthanasia and displayed progressive bony encapsulation of the screw. All rats inoculated with S. epidermidis-colonized screws were culture-positive and displayed minor changes in peri-implant bone, characteristic of subclinical infection. Five of the 17 rats in the C. acnes inoculated group were culture positive at euthanasia and displayed bone changes at the interface of the screw and bone, but not deeper in the peri-implant bone. Dynamic histomorphometry revealed significant differences in osseointegration, bone remodeling and periosteal reactions between groups that were not measurable by visual observation of still microCT images. Our study illustrates the added value of merging 3D microCT data from subsequent timepoints and producing inherently richer 4D data for the detection and characterization of subclinical orthopedic infections, whilst also reducing animal use.