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Bone fractures at weight-bearing sites are challenging to treat due to the difficulty in maintaining articular congruency. An ideal biomaterial for fracture repair near articulating joints sets rapidly after implantation, stabilizes the fracture with minimal rigid implants, stimulates new bone formation, and remodels at a rate that maintains osseous integrity. Consequently, the design of biomaterials that mechanically stabilize fractures while remodeling to form new bone is an unmet challenge in bone tissue engineering. In this study, we investigated remodeling of resorbable bone cements in a stringent model of mechanically loaded tibial plateau defects in sheep. Nanocrystalline hydroxyapatite-poly(ester urethane) (nHA-PEUR) hybrid polymers were augmented with either ceramic granules (85% β-tricalcium phosphate/15% hydroxyapatite, CG) or a blend of CG and bioactive glass (BG) particles to form a settable bone cement. The initial compressive strength and fatigue properties of the cements were comparable to those of non-resorbable poly(methyl methacrylate) bone cement. In animals that tolerated the initial few weeks of early weight-bearing, CG/nHA-PEUR cements mechanically stabilized the tibial plateau defects and remodeled to form new bone at 16 weeks. In contrast, cements incorporating BG particles resorbed with fibrous tissue filling the defect. Furthermore, CG/nHA-PEUR cements remodeled significantly faster at the full weight-bearing tibial plateau site compared to the mechanically protected femoral condyle site in the same animal. These findings are the first to report a settable bone cement that remodels to form new bone while providing mechanical stability in a stringent large animal model of weight-bearing bone defects near an articulating joint.
Copyright © 2018 Elsevier Ltd. All rights reserved.
The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.
PMMA particles released from bone implants are considered major contributor to osteolysis and subsequent implant failure. Although the ensuing inflammatory response has been described, the mechanisms underlying PMMA particulate-induced osteolysis remain enigmatic. In previous studies, we have established that activation of Nuclear factor kappa-B (NF-κB) and MAP kinase pathways plays a central role in the pathogenesis of inflammatory osteolysis. Specifically, we have shown that impeding IKK complex assembly, and thus subsequent NF-κB activation, dampens particle-induced osteolysis. The IKK complex consists of IKKα, IKKβ, and IKKγ, also known as NEMO. NEMO has no catalytic activity and serves as a scaffold protein facilitating assembly and distal activation of NF-κB signaling. In fact, blocking binding of NEMO with IKKα/β abolishes NF-κB activity. In the current study, we identify Lysine 392 residue in NEMO as crucial mediator of PMMA particle-induced inflammatory osteoclastogenesis and osteolysis. Using mice in which NEMO-K392R mutation has been introduced, we provide evidence that PMMA-induced osteoclasts and osteolytic responses are impaired. Furthermore, we show that this impairment is likely due to poor activation of NF-κB and Erk, but not other MAP kinases. Our findings suggest that NEMO Lysine392, a well-established K63-linked polyubiquitination site, is an important mediator of PMMA-induced osteolysis. Therefore, this NEMO motif should be considered as a target to combat PMMA particle-induced osteolysis.
Copyright © 2011 Orthopaedic Research Society.
Polymethyl methacrylate (PMMA) and related cosmetic ingredients methyl methacrylate crosspolymer and methyl methacrylate/glycol dimethacrylate crosspolymer are polymers that function as film formers and viscosity-increasing agents in cosmetics. The Food and Drug Administration (FDA) determination of safety of PMMA use in several medical devices, which included human and animal safety data, was used as the basis of safety of PMMA and related polymers in cosmetics by the Cosmetic Ingredient Review (CIR) Expert Panel. The PMMA used in cosmetics is substantially the same as in medical devices. The Panel concluded that these ingredients are safe as cosmetic ingredients in the practices of use and concentrations as described in this safety assessment.
Polychromatic phase-contrast radiography differs from traditional (absorption-only) radiography in that the method requires at least a partially coherent x-ray source and the resulting images contain information about the phase shifts of x-rays in addition to the traditional absorption information. In a typical embodiment, this effect results in a measurable enhancement in image contrast at the edges of objects. In this study, a phase-contrast imaging system was adapted to allow an object to be imaged at multiple projections, and these projections were used to generate phase-contrast computed tomography images. The images obtained with this technique show edge enhancements surrounding the objects within the image.
OBJECTIVE - The purpose of our study was to correlate findings of prevertebroplasty MRI with outcomes in the treatment of chronic osteoporotic compression fractures.
MATERIALS AND METHODS - Forty-five patients with osteoporotic spinal compression fractures of more than 1 year's duration were treated with vertebroplasty. Changes in pain and mobility were assessed by follow-up of 1-28 months. Preprocedural MR images were reviewed using the Modic criteria and were correlated with outcomes.
RESULTS - Fifteen patients (33%) had marrow edema on MRI and 30 (67%) of the 45 patients did not. All 15 of the patients with edema had clinical benefit: six patients (40%) achieved complete relief and nine (60%) experienced symptom improvement. Ten patients (67%) had improvement in mobility, and the remaining five patients (33%) had no change. Of patients with no marrow edema (n = 30), five (17%) had complete resolution of pain, 19 (63%) were improved, and six (20%) were unchanged. None had worsening of their symptoms. Mobility was improved in 17 (57%) and unchanged in 10 (33%). Mobility was diminished in three patients (10%). In two cases, impaired mobility was due to causes other than spine disorders.
CONCLUSION - Most (87%) of the 45 patients with compression fractures older than 1 year derived clinical benefit from vertebroplasty irrespective of MRI findings. Although 100% of patients with bone marrow edema had clinical benefit, no direct correlation was seen between symptom resolution and the presence of edema on preprocedural MRI. In our experience, absence of abnormal marrow signal does not definitively predict the outcome of vertebroplasty in chronic fractures.
Recently, a new theory of phase-contrast imaging has been proposed by Wu and Liu [Med. Phys. 31, 2378-2384 (2004)]. This theory, based upon Wigner distributions, provides a much stronger foundation for the evaluation of phase-contrast imaging systems than did the prior theories based upon Fresnel-Kirchhoff diffraction theory. In this paper, we compare results of measurements made in our laboratory of phase contrast for different geometries and tube voltages to the predictions of the Wu and Liu model. In our previous publications, we have used an empirical measurement (the edge enhancement index) to parametrize the degree of phase-contrast effects in an image. While the Wu and Liu model itself does not predict image contrast, it does measure the degree of phase contrast that the system can image for a given spatial frequency. We have found that our previously published experimental results relating phase-contrast effects to geometry and x-ray tube voltage are consistent with the predictions of the Wu and Liu model.
The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.