Reactions of bone, liver and kidney tissues to orthopaedic implants with silver nanoparticle doped hydroxyapatite coatings: microscopic examination in a rabbit model

2018 ◽  
Vol 87 (2) ◽  
pp. 99-105
Author(s):  
Łukasz Łapaj ◽  
Waldemar Woźniak ◽  
Paweł Chodór ◽  
Jan Zabrzyński ◽  
Łukasz Paczesny

Background: Periprosthetic joint infections are severe complications of arthroplasty, difficult to manage due to biofilm formation on the components. Recently, the use of silver nanoparticles (SNs) has emerged as a method of preventing biofilm formation on orthopaedic implants, however little is known about the systematic toxicity of SNs.Aim: This study used a rabbit model to examine the tissue response of bone, liver and kidney to prototype components with SN doped hydroxyapatite (HA) coatings.Materials and methods: Twelve prototype implants (six with HA, six with SN doped HA coatings) were implanted into the femora of twelve New Zealand Rabbits. After 6 weeks, the animals were euthanised, their femora and samples of livers and kidneys harvested to prepare microscopic slides. The slides were examined for the presence inflammatory or toxic reactions to SNs, implants were examined using scanning electron microscopy (SEM) to determine structural changes related to implantation and verify retention of SNs in vivo.Results: SEM demonstrated that SNs formed submicron conglomerates, which were retained after 6 weeks in vivo and did not interfere with osseointegration. Histologic studies of bone fragments demonstrated no signs of acute toxicity and inflammation. No inflammatory reaction was observed in kidneys, although in some samples signs of acute renal failure related to euthanasia were found. No severe toxic reaction was found in liver samples, however fatty degeneration of liver was found in some animals.Conclusions: This study documented good osteointegration of implants with SN doped HA coatings with low systematic toxicity of SNs.

2012 ◽  
Vol 302 (8) ◽  
pp. H1625-H1635 ◽  
Author(s):  
Leroy L. Cooper ◽  
Katja E. Odening ◽  
Min-Sig Hwang ◽  
Leonard Chaves ◽  
Lorraine Schofield ◽  
...  

Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5–9 mo) and old (3.5–6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 ± 0.36 vs. old, 4.35 ± 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 ± 0.5 vs. 4.95 ± 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 ± 4.2 vs. 33.14 ± 8.4 mmHg/ml, P < 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 ± 2.5 vs. 31.9 ± 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age-related changes that predispose the aging heart to arrhythmias and SCD.


2019 ◽  
Vol 8 (6) ◽  
pp. 266-274
Author(s):  
I. Palmer ◽  
S. A. Clarke ◽  
F. J Buchanan

Objectives Bioresorbable orthopaedic devices with calcium phosphate (CaP) fillers are commercially available on the assumption that increased calcium (Ca) locally drives new bone formation, but the clinical benefits are unknown. Electron beam (EB) irradiation of polymer devices has been shown to enhance the release of Ca. The aims of this study were to: 1) establish the biological safety of EB surface-modified bioresorbable devices; 2) test the release kinetics of CaP from a polymer device; and 3) establish any subsequent beneficial effects on bone repair in vivo. Methods ActivaScrew Interference (Bioretec Ltd, Tampere, Finland) and poly(L-lactide-co-glycolide) (PLGA) orthopaedic screws containing 10 wt% β-tricalcium phosphate (β-TCP) underwent EB treatment. In vitro degradation over 36 weeks was investigated by recording mass loss, pH change, and Ca release. Implant performance was investigated in vivo over 36 weeks using a lapine femoral condyle model. Bone growth and osteoclast activity were assessed by histology and enzyme histochemistry. Results Calcium release doubled in the EB-treated group before returning to a level seen in untreated samples at 28 weeks. Extensive bone growth was observed around the perimeter of all implant types, along with limited osteoclastic activity. No statistically significant differences between comparative groups was identified. Conclusion The higher than normal dose of EB used for surface modification did not adversely affect tissue response around implants in vivo. Surprisingly, incorporation of β-TCP and the subsequent accelerated release of Ca had no significant effect on in vivo implant performance, calling into question the clinical evidence base for these commercially available devices. Cite this article: I. Palmer, S. A. Clarke, F. J Buchanan. Enhanced release of calcium phosphate additives from bioresorbable orthopaedic devices using irradiation technology is non-beneficial in a rabbit model: An animal study. Bone Joint Res 2019;8:266–274. DOI: 10.1302/2046-3758.86.BJR-2018-0224.R2.


2017 ◽  
Vol 204 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Bernard Rousseau ◽  
Tsuyoshi Kojima ◽  
Carolyn K. Novaleski ◽  
Emily E. Kimball ◽  
Carla V. Valenzuela ◽  
...  

We investigated the timeline of tissue repair of vocal fold epithelium after acute vibration exposure using an in vivo rabbit model. Sixty-five New Zealand white breeder rabbits were randomized to 120 min of modal- or raised-intensity phonation. After the larynges were harvested at 0, 4, 8, and 24 h, and at 3 and 7 days, the vocal fold tissue was evaluated using electron microscopy and quantitative real-time polymerase chain reaction. There was an immediate decrease in the microprojection depth and height following raised-intensity phonation, paired with upregulation of cyclooxygenase-2. This initial 24-h period was also characterized by the significant downregulation of junction proteins. Interleukin 1β and transforming growth factor β1 were upregulated for 3 and 7 days, respectively, followed by an increase in epithelial cell surface depth at 3 and 7 days. These data appear to demonstrate a shift from inflammatory response to the initiation of a restorative process in the vocal fold epithelium between 24 h and 3 days. Despite the initial damage from raised-intensity phonation, the vocal fold epithelium demonstrates a remarkable capacity for the expeditious recovery of structural changes from transient episodes of acute phonotrauma. While structurally intact, the return of functional barrier integrity may be delayed by repeated episodes of phonotrauma and may also play an important role in the pathophysiology of vocal fold lesions.


2007 ◽  
Vol 102 (3) ◽  
pp. 1273-1280 ◽  
Author(s):  
Jaime F. Mata ◽  
Talissa A. Altes ◽  
Jing Cai ◽  
Kai Ruppert ◽  
Wayne Mitzner ◽  
...  

The apparent diffusion coefficients (ADCs) of hyperpolarized 3He and 129Xe gases were measured in the lungs of rabbits with elastase-induced emphysema and correlated against the mean chord length from lung histology. In vivo measurements were performed at baseline and 2, 4, 6, and 8 wk after instillation of elastase (mild and moderate emphysema groups) or saline (control group). ADCs were determined from acquisitions that used two b values. To investigate the effect of b value on the results, b-value pairs of 0 and 1.6 s/cm2 and 0 and 4.0 s/cm2 were used for 3He, and b-value pairs of 0 and 5.0 s/cm2 and 0 and 10.0 s/cm2 were used for 129Xe. At 8 wk after instillation, the rabbits were euthanized, and the lungs were analyzed histologically and morphometrically. ADCs for the rabbits in the control group did not change significantly from baseline to week 8, whereas ADCs for the rabbits in the emphysema groups increased significantly ( P < 0.05) for all gas and b-value combinations except 129Xe with the b-value pair of 0 and 5.0 s/cm2. The largest percent change in mean ADC from baseline to week 8 (15.3%) occurred with 3He and the b-value pair of 0 and 1.6 s/cm2 for rabbits in the moderate emphysema group. ADCs (all b values) were strongly correlated ( r = 0.62–0.80, P < 0.001) with mean chord lengths from histology. These results further support the ability of diffusion-weighted MRI with hyperpolarized gases to detect regional and global structural changes of emphysema within the lung.


2020 ◽  
Vol 18 ◽  
Author(s):  
Alireza Partoazar ◽  
Fatemeh Rahmani Bideskan ◽  
Nasrin Takzaree ◽  
Mohammad Mehdi Soltan Dallal

Background: Infectious diseases, whether intracellular or extracellular infections, biofilm-mediated, or medical device- associated have always been a global problem in public health causing millions of deaths each year. The aim of this study was to evaluate the antibiofilm activity of ZnO/ZeoNC against K. pneumoniae along with biocompatibility of nanocomposite in vivo model. Objective: The formation of biofilm by K. pneumoniae in the catheter-associated urinary tract causes a nosocomial infection. In this regard, antimicrobial nanomaterials have emerged as potent effective agents against biofilm formation. Nevertheless, nanoparticles have already been a challenge with possible side effects such as inflammation. The ZnO/ZeoNC may exhibit anti-biofilm property with minimal adverse effects. Methods: The biofilm formation of K. pneumoniae strains was exposed to ZnO/ZeoNC and then SEM imaging was performed for morphological investigation of bacteria in biofilm state. The quantity of mice tissue response to ZnO/ZeoNC embedded polyethylene tube also analyzed on the tissue of mice during the 30-day experiment. Results: The results of this study showed that ZnO/ZeoNC has the significant antibiofilm activity against K. pneumoniae strains in its sublethal doses. The ZnO/ZeoNC also caused deformation on K. pneumoniae biofilm. In addition, ZnO/ZeoNC also reduced inflammatory response in cell tissue of rats subjected to polyethylene tube. Conclusion: ZnO/ZeoNC can be used potentially against the infections due to K. pneumonia biofilm without irritability on the biotic surface such as urinary tract.


2006 ◽  
Vol 74 (7) ◽  
pp. 3804-3816 ◽  
Author(s):  
Pranab K. Mukherjee ◽  
Sotohy Mohamed ◽  
Jyotsna Chandra ◽  
Duncan Kuhn ◽  
Shuqing Liu ◽  
...  

ABSTRACT Candida biofilms formed on indwelling medical devices are increasingly associated with severe infections. In this study, we used proteomics and Western and Northern blotting analyses to demonstrate that alcohol dehydrogenase (ADH) is downregulated in Candida biofilms. Disruption of ADH1 significantly (P = 0.0046) enhanced the ability of Candida albicans to form biofilm. Confocal scanning laser microscopy showed that the adh1 mutant formed thicker biofilm than the parent strain (210 μm and 140 μm, respectively). These observations were extended to an engineered human oral mucosa and an in vivo rat model of catheter-associated biofilm. Inhibition of Candida ADH enzyme using disulfiram and 4-methylpyrazole resulted in thicker biofilm (P < 0.05). Moreover, biofilms formed by the adh1 mutant strain produced significantly smaller amounts of ethanol, but larger amounts of acetaldehyde, than biofilms formed by the parent and revertant strains (P < 0.0001), demonstrating that the effect of Adh1p on biofilm formation is mediated by its enzymatic activity. Furthermore, we found that 10% ethanol significantly inhibited biofilm formation in vitro, with complete inhibition of biofilm formation at ethanol concentrations of ≥20%. Similarly, using a clinically relevant rabbit model of catheter-associated biofilm, we found that ethanol treatment inhibited biofilm formation by C. albicans in vivo (P < 0.05) but not by Staphylococcus spp. (P > 0.05), indicating that ethanol specifically inhibits Candida biofilm formation. Taken together, our studies revealed that Adh1p contributes to the ability of C. albicans to form biofilms in vitro and in vivo and that the protein restricts biofilm formation through an ethanol-dependent mechanism. These results are clinically relevant and may suggest novel antibiofilm treatment strategies.


Author(s):  
Brandon W. Kao ◽  
Elana Meer ◽  
Thomas A. Barbolt ◽  
Richard A. Lewis ◽  
Iqbal Ike Ahmed ◽  
...  

Abstract Background Glaucoma is the leading cause of blindness worldwide. Glaucoma drainage devices and minimally invasive glaucoma surgeries (MIGS) often present with tradeoffs in safety and durability of efficacy. Using a rabbit model, we examined the biocompatibility and feasibility of VisiPlate, a novel, ultrathin, tubeless subconjunctival shunt comprised of a network of microchannels. Methods Six naive female New Zealand White rabbits received implants (three only in the right eye with contralateral eye untreated and three in both eyes) composed of a 400-nm-thick aluminum oxide core coated with 2 µm of parylene-C, manufactured with microelectromechanical systems (MEMS) techniques. Tonometry, slit lamp exam, clinical exam, fluorescein patency testing, and histopathology were performed. Results VisiPlate demonstrated IOP-lowering of 20–40% compared to baseline at each time point over the course of 3 months in the nine implanted eyes. All eyes developed blebs over the implant, and fluorescein testing demonstrated fluid patency at 22 days post-implantation. Slit lamp and clinical observations showed that VisiPlate was well tolerated, with low levels of conjunctival congestion, conjunctival swelling, aqueous flare, hyphema, and iris involvement from surgery that resolved over time. At sacrifice time points of 93 days and 180 days, the only notable observations were mild levels of conjunctival congestion in implanted eyes. Histopathology showed minimal tissue response and no obvious inflammation, fibrosis, or necrosis around the implant. Conclusions The results of this in vivo study demonstrate the biocompatibility and IOP-lowering effect of a multichannel, ultrathin subconjunctival shunt in a rabbit model. The data suggest that VisiPlate may safely enhance aqueous outflow and significantly reduce intraocular pressure.


Author(s):  
S. Phyllis Steamer ◽  
Rosemarie L. Devine

The importance of radiation damage to the skin and its vasculature was recognized by the early radiologists. In more recent studies, vascular effects were shown to involve the endothelium as well as the surrounding connective tissue. Microvascular changes in the mouse pinna were studied in vivo and recorded photographically over a period of 12-18 months. Radiation treatment at 110 days of age was total body exposure to either 240 rad fission neutrons or 855 rad 60Co gamma rays. After in vivo observations in control and irradiated mice, animals were sacrificed for examination of changes in vascular fine structure. Vessels were selected from regions of specific interest that had been identified on photomicrographs. Prominent ultrastructural changes can be attributed to aging as well as to radiation treatment. Of principal concern were determinations of ultrastructural changes associated with venous dilatations, segmental arterial stenosis and tortuosities of both veins and arteries, effects that had been identified on the basis of light microscopic observations. Tortuosities and irregularly dilated vein segments were related to both aging and radiation changes but arterial stenosis was observed only in irradiated animals.


1982 ◽  
Vol 47 (03) ◽  
pp. 269-274 ◽  
Author(s):  
R A G Smith ◽  
R J Dupe ◽  
P D English ◽  
J Green

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.


Author(s):  
Nurgozhin T. ◽  
Sergazy S. H. ◽  
Adilgozhina G. ◽  
Gulyayev A. ◽  
Shulgau Z. ◽  
...  

Objective:This study investigates the hepatoprotective effect and the antioxidant role of polyphenol concentrate in the experimental model of carbon tetrachloride (CCl4) induced toxicity. Methods: Antioxidant activity of Cabernet Sauvignon grape polyphenol were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), 2,2’-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS.+). In addition, the effects of polyphenol concentrate on the survival of Wistar rats in the toxicity model, was also investigated. The polyphenol concentrate was administered for 5 five days prior to injection of carbon tetrachloride in a sub-lethal dose of 300 mg/kg of animal body weight in order to perform histological examinations of the liver and kidney, and detect the levels of AST, ALT and bilirubin. Results: Administration of polyphenol concentrate increased animal survival in the experimental model. Moreover, the intragastric administration of polyphenol concentrate prior to the initiation of the experimental model of toxicity, which was caused by a sub-lethal CCl4 dose, reduced morphological injuries in the liver and kidney, decreased the AST and ALT levels of the blood serum. Discussion and conclusion: Our data demonstrate that polyphenol concentrate possesses an antioxidant potential both in vitro and in vivo by reducing antioxidant stress that was caused by CCl4 administration into rats.


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