Aims. Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation. Methods. A
We hypothesised that diet-induced obesity (DIO) would result in inferior enthesis healing in a
Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. To date, there are no animal models that can fully recapitulate how a biofilm is challenged in vivo in the setting of GN-PJI. The purpose of this study is to establish a clinically representative GN-PJI in vivo model that can reliably depict biofilm formation on titanium implant surface. We hypothesized that the biofilm formation on the implant surface would affect the ability of the implant to be osseointegrated. The model was developed using a 3D-printed, medical-grade titanium (Ti-6Al-4V), monoblock, cementless hemiarthroplasty hip implant. This implant was used to replace the femoral head of a Sprague-Dawley
Introduction. Gram-negative prosthetic joint infections (GN-PJI) present unique challenges in management due to their distinct pathogenesis of biofilm formation on implant surfaces. The purpose of this study is to establish a clinically representative GN-PJI model that can reliably recapitulate biofilm formation on titanium implant surface in vivo. We hypothesized that biofilm formation on an implant surface will affect its ability to osseointegrate. Methods. The model was developed using 3D-printed titanium hip implants, to replace the femoral head of male Sprague-Dawley rats. GN-PJI was induced using two bioluminescent Pseudomonas aeruginosa strains: a reference strain (PA14-lux) and a mutant biofilm-defective strain (ΔflgK-lux). Infection was monitored in real-time using the in vivo imaging system (IVIS) and Magnetic Resonance Imaging (MRI). Bacterial loads on implant surface and in periprosthetic tissues were quantified utilizing viable-colony-count. Field-emission scanning-electron-microscopy of the explanted implants was used to visualize the biofilm formation at the bone-implant-interface. The implant stability, as an outcome, was directly assessed by quantifying the osseointegration in vitro using microCT scan, and indirectly assessed by identifying the gait pattern changes using DigiGait. TM. system in vivo. Results. Localized infection was established within the hip joint and was followed by IVIS in real-time. There was a quantitative and qualitative difference in the bacterial load and biofilm formation between PA14-lux and ΔflgK-lux. This difference in the ability to persist in the model between the two strains was reflected in the gait pattern and implant osseointegration. Conclusions. We developed a novel uncemented hip hemiarthroplasty, GN-PJI
In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized
We investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a
Aim. In this study we investigated the effects of non-steroidal anti-inflammatory drugs (NSAIDs) with different cyclooxygenase (COX) selectivity on orthopaedic device-related infections (ODRIs) in a
Purpose. Angiogenesis and osteogenesis are essential for bone growth, fracture repair, and bone remodeling. VEGF has an important role in bone repair by promoting angiogenesis and osteogenesis. In our previous study, endothelial progenitor cells (EPCs) promoted bone healing in a
Currently, there is no animal model in which
to evaluate the underlying physiological processes leading to the heterotopic
ossification (HO) which forms in most combat-related and blast wounds.
We sought to reproduce the ossification that forms under these circumstances
in a
Aim. Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone of perioperative pain management in orthopedic trauma surgery, although concerns persist regarding the potential impact of these drugs on fracture healing. Furthermore, NSAIDs may also exert an influence on host immune defenses, which may also be important in the context of infection treatment. However, this has been very much under-investigated in the clinical and scientific literature. The aim of this study was to determine the impact of NSAIDs on the course of an orthopedic device-related infection (ODRI) and its response to antibiotic therapy in a
Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO4 to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO4 were created using intensity thresholding at 3000HU (~736mgHA/cm3) and 10000HU (~2420mgHA/cm3), respectively. Non-specific BaSO4 was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO4 volume to the sum of BaSO4 and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction ( Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality.
Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO4 to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO4 were created using intensity thresholding at 3000HU (~736mgHA/cm3) and 10000HU (~2420mgHA/cm3), respectively. Non-specific BaSO4 was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO4 volume to the sum of BaSO4 and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction ( Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality.
Low back pain is more common in women than men, yet most studies of intervertebral disc (IVD) degeneration do not address sex differences. In humans, there are sex differences in spinal anatomy and degenerative changes in biomechanics, and animal models of chronic pain have demonstrated sex differences in pain transduction. However, there are few studies investigating sex differences in annular puncture IVD degeneration models. IVD puncture is known to result in progressive biomechanical alterations, but whether these IVD changes correlate with pain is unknown. This study used a
To set up an osteosarcoma
Prosthetic joint infection (PJI) is a complex disease that causes significant damage to the peri-implant tissue. Developing an animal model that is clinically relevant in depicting this disease process is an important step towards developing novel successful therapies. In this study, we have performed a thorough histologic analysis of peri-implant tissue harvested post Staphylococcus aureus (S. aureus) infection of a cemented 3D-printed titanium hip implant in rats. Sprague-Dawley rats underwent left hip cemented 3D-printed titanium hemiarthroplasty via posterior approach under general anesthesia. Four surgeries were performed for the control group and another four for the infected group. The hip joint was inoculated with 5×109 CFU/mL of The histologic analysis revealed strong resemblance to tissue changes in the clinical setting of chronic PJI. IHC demonstrated the extent of bacterial spread within the peri-implant tissue away from the site of infection. The H&E and MT stains showed 5 main features in infected bone: 1) increased PMNs, 2) fibrovascular inflammation, 3) bone necrosis, and 4) increased osteoclasts 5) fibrosis of muscular tissue and cartilage. Micro CT data showed significantly more osteolysis present around the infected prosthesis compared to control (surgery with no infection). This is the first clinically relevant PJI animal model with detailed histologic analysis that strongly resembles the clinical tissue pathology of chronic PJI. This model can provide a better understanding of how various PJI therapies can halt or reverse peri-implant tissue damage caused by infection.
Bone marrow concentrates are being used to augment soft tissue healing. However, only 0.01% of these cells meet the criteria of a mesenchymal stem cell (MSC), which likely accounts for the variability in reported results. Previous studies using an established
Sclerostin is a negative regulator of osteoblast differentiation and bone formation, probably through inhibition of the Wnt pathway. Distraction osteogenesis (DO) can be complicated by osteopenia and poor anabolic response, which may benefit from anabolic therapy. Sclerostin antibody (Scl-Ab) has been reported to stimulate bone formation and restore bone mass and strength in aged ovariectomised rats as well as to enhance fracture healing. We sought to examine the effects of Scl-Ab in a
INTRODUCTION. Rotator cuff tears are common injuries which often require surgical repair. Unfortunately, repairs often fail [1] and improved repair strength is essential. P2 Porous titanium (DJO Surgical, Austin TX) has been shown to promote osseointegration [2,3] and subdermal integration [4]. However, the ability of P2Porous titanium to aid in supraspinatus tendon-to-bone repair has not been evaluated. Therefore, the purpose of this study was to investigate P2 implants used to augment supraspinatus tendon-to-bone repair in a
To test the hypothesis that: CERAMENT[™]|G (C-G) would improve new bone growth and decrease infection rate after debridement as compared with 1) CERAMENT|BONE VOID FILLER (CBVF) and 2) no void filler in a
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods