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.

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.

Growth modulation of angular deformities with a novel constant force implant concept-preclinical results.

PURPOSE: Varus-valgus deformities in children and adolescents are often corrected by temporary hemi-epiphysiodesis, in which the physis is bridged by an implant to inhibit growth. With standard implant solutions, the acting forces cannot be regulated, rendering the correction difficult to control. Furthermore, the implant load steadily increases with ongoing growth potentially leading to implant-related failures. A novel implant concept was developed applying a controlled constant force to the physis, which carries the potential to avoid these complications. The study aim was to proof the concept in vivo by analyzing the effect of three distinct force levels on the creation of varus deformities. METHODS: The proposed implant is made of a conventional cerclage wire and features a twisted coil that unwinds with growth resulting in an implant-specific constant force level. The proximal medial tibial physes of 18 lambs were treated with the implant and assigned to three groups distinct by the force level of the implant (200 N, 120 N, 60 N). RESULTS: The treatment appeared safe without implant-related failures. Deformity creation was statistically different between the groups and yielded on average 10.6° (200 N), 4.8° (120 N) and 0.4° (60 N) over the treatment period. Modulation rates were 0.51°/mm (200 N), 0.23°/mm (120 N) and 0.05°/mm (60 N) and were constant throughout the treatment. CONCLUSION: By means of the constant force concept, controlled growth modulation appeared feasible in this preclinical experiment. However, clinical trials are necessary to confirm whether the results are translatable to the human pathological situation.

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.

Relative effects of age on implant integration in a rat model: A longitudinal in vivo microct study.

The effect of age on implant fixation in bone is not always considered during the design of preclinical models. The decision on animal's age is often related to practical or historical reasons, which ultimately may affect the reproducibility of results. This study aimed to quantify the effect of age by monitoring the fixation of contrast-enhanced PEEK screws in rats, hypothesizing that the kinetics of fixation is impaired in older animals but that age effects are less severe than osteoporotic effects. The time course of implant fixation was investigated in healthy rats at 24, 40, and 60 weeks of age; and in ovariectomized rats. Implant fixation was monitored using in-vivo microCT and dynamic histomorphometry during 1 month. The rats were euthanized 28 days post screw insertion. The data was analyzed both in absolute value and after normalization to baseline bone mass. In absolute terms, greater age had a detrimental effect on bone implant contact, bone fraction, implant stiffness, and bone remodeling but less than ovariectomy. Interestingly, once data was normalized to baseline bone mass this effect disappeared, suggesting that the physiologic response to implant placement was not affected by age. In conclusion, implant fixation kinetics is less affected by age than by baseline bone mass in this rat model. Animals of different ages can therefore be compared but data must be construed relatively to baseline bone mass and not in absolute terms. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-12, 2018.