scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

scholarly journals Evaluation of a polymeric composite bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2020 ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Prolonged Release ◽  
Segmental Bone Defect ◽  
Complete Eradication ◽  
Bone Filler ◽  
Viable Bacteria ◽  
Segmental Bone ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane (dPU), nano-sized hydroxyapatite (nHA), and decellularized bovine bone particles (DBP). In this report we describe the results of studies aimed at evaluating the use of this scaffold as a means of local antibiotic delivery for the prevention of infection in a segmental bone defect contaminated with Staphylococcus aureus. We evaluated two different scaffold formulations that contained the same components in the same ratios but differed from each other with respect to overall porosity and therefore surface area. Studies done with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity was correlated with increased uptake and prolonged release of all three antibiotics. Vancomycin could be passively loaded into either scaffold formulation in an amount sufficient to prevent infection, as evidenced by the complete eradication of viable bacteria from the surgical site of most animals in a rabbit model of a contaminated mid-radial segmental bone defect. Even in those few cases in which complete eradication was not achieved, the number of viable bacteria present in the bone was significantly reduced comparison to untreated controls. There was also no radiographic evidence of osteomyelitis in any rabbit treated with vancomycin-loaded scaffold. Microcomputed tomography (μCT) of bone defects up to 84 days of exposure to scaffolds with and without vancomycin also demonstrated that the addition of vancomycin even in the highest concentration did not significantly diminish the osteogenic properties of either scaffold formulation. Together, these results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery.

scholarly journals Potential Use of Eggshell as Bone Graft Compared with Bovine for Bone Defect: A Systematic Review Study

2021 ◽  
Vol 9 (F) ◽  
pp. 470-473
Author(s):  
Hanif Andhika Wardhana ◽  
Mujaddid Idulhaq ◽  
Rhyan Darma Saputra ◽  
Rieva Ermawan ◽  
Musa Fasa Roshada
Keyword(s):  
Systematic Review ◽  
Bone Graft ◽  
Bone Regeneration ◽  
Bone Defect ◽  
Clinical Performance ◽  
Bone Grafts ◽  
Bone Tissue Regeneration ◽  
In Vivo Studies ◽  
Bovine Bone

Background : The use of Bone Graft in the management of Bone Defect is a challenge in the world of orthopedics. Recently, eggshell containing hydroxyapatite has become a new hope in the use of an economical and efficient bone graft in the treatment of bone defects. The aim of this systematic review was to explore the available literature on the clinical performance of eggshells as bone grafts in guided bone regeneration. Method : Two databases (PubMed and Cochrane) were searched from January 2010 to September 2020. Clinical trials using eggshells as bone grafts were included in the review. Animal and in vivo studies were excluded from the review. Results : A total of 202 studies were taken, then screened and 15 studies finally included. Clinical and radiological evaluations show complete recovery after the procedure. Comparison with synthetic hydroxyapatite shows similar healing characteristics. Conclusion : Eggshell compared to bovine showed no difference in bone healing. Within the limitations of the included studies, eggshells can be used safely and efficiently in integrated bone regeneration procedures. Keywords: Bone tissue regeneration; eggshell; bovine; bone defect; bone graft  

Lithium-incorporated deproteinized bovine bone substitute improves osteogenesis in critical-sized bone defect repair

2018 ◽  
Vol 32 (10) ◽  
pp. 1421-1434 ◽  
Author(s):  
Hongzhang Guo ◽  
Changde Wang ◽  
Jixiang Wang ◽  
Yufang He
Keyword(s):  
Computed Tomography ◽  
Bone Defect ◽  
Bone Substitute ◽  
In Vivo Studies ◽  
Calcium Deposition ◽  
Bovine Bone ◽  
Bone Defect Repair ◽  
Defect Repair ◽  
Deproteinized Bovine Bone

This study aimed to explore the surface modification of deproteinized bovine bone using lithium-ion and evaluate its efficacy on osteogenesis improvement and critical-sized bone defect repair. Hydrothermal treatment was performed to produce lithium-incorporated deproteinized bovine bone. In vitro study, human osteosarcoma cell MG63 (MG63) was cultured with the bone substitute to evaluate the cell viability and then calcium deposition was measured to analyze the osteogenesis. In vivo studies, male adult goats were chosen to build critical-sized bone defect model and randomly divided into three groups. The goats were treated with autogenous cancellous bone, lithium-incorporated deproteinized bovine bone, and deproteinized bovine bone. Animals were evaluated using radiological analysis including X-ray, computed tomography, and Micro-CT; histological methods involving hematoxylin–eosin dyeing, Masson dyeing, and immunofluorescence detection at 4 and 12 weeks after surgery were carried out. According to the results, lithium-incorporated deproteinized bovine bone produced nano-structured surface layer. The lithium-incorporated deproteinized bovine bone could promote the osteoblast proliferation and increase the calcium deposition. In vivo studies, radiographic results revealed that lithium-incorporated deproteinized bovine bone scaffolds provided better performance in terms of mean gray values of X films, mean pixel values of computed tomography films, and bone volume and trabecular thickness of micro-computed tomography pictures when compared with the deproteinized bovine bone group. In addition, histological analysis showed that the lithium-incorporated deproteinized bovine bone group also significantly achieved larger new bone formation area. At the same time, when the expression of osteogenic factors in vivo was evaluated, runt-related transcription factor 2 (Runx2) and collagen type one (Col-1) were expressed more in lithium-incorporated deproteinized bovine bone group than those in deproteinized bovine bone group. However, the bone defect repair effect using autograft is still a little better than that of lithium-incorporated deproteinized bovine bone substitute based on our results. In conclusion, surface lithium-incorporated deproteinized bovine bone achieved improvement of osteogenesis effect and could enhance the new bone formation in critical-sized bone defects.

Heparin-mediated antibiotic delivery from an electrochemically-aligned collagen sheet

2021 ◽  
pp. 1-12
Author(s):  
Olivia T. Cheng ◽  
Andrew P. Stein ◽  
Eric Babajanian ◽  
Kathryn R. Hoppe ◽  
Shawn Li ◽  
...  
Keyword(s):  
High Performance ◽  
Inhibitory Concentration ◽  
Medical Implants ◽  
Implantable Medical Devices ◽  
Antibiotic Solution ◽  
Inhibition Zones ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

BACKGROUND: Implantable medical devices and hardware are prolific in medicine, but hardware associated infections remain a major issue. OBJECTIVE: To develop and evaluate a novel, biologic antimicrobial coating for medical implants. METHODS: Electrochemically compacted collagen sheets with and without crosslinked heparin were synthesized per protocol developed by our group. Sheets were incubated in antibiotic solution (gentamicin or moxifloxacin) overnight, and in vitro activity was assessed with five-day diffusion assays against Pseudomonas aeruginosa. Antibiotic release overtime from gentamicin infused sheets was determined using in vitro elution and high performance liquid chromatography (HPLC). RESULTS: Collagen-heparin-antibiotic sheets demonstrated larger growth inhibition zones against P. aeruginosa compared to collagen-antibiotic alone sheets. This activity persisted for five days and was not impacted by rinsing sheets prior to evaluation. Rinsed collagen-antibiotic sheets did not show any inhibition zones. Elution of gentamicin from collagen-heparin-gentamicin sheets was slow and remained above the minimal inhibitory concentration for gentamicin sensitive organisms for 29 days. Conversely, collagen-gentamicin sheets eluted their antibiotic payload within 24 hours. Overall, heparin associated sheets demonstrated larger inhibition zones against P. aeruginosa and prolonged elution profile via HPLC. CONCLUSION: We developed a novel, local antibiotic delivery system that could be used to coat medical implants/hardware in the future and reduce post-operative infections.

scholarly journals Melt-Cast Films Significantly Enhance Triamcinolone Acetonide Delivery to the Deeper Ocular Tissues

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 158
Author(s):  
Akshaya Tatke ◽  
Narendar Dudhipala ◽  
Karthik Janga ◽  
Bhavik Soneta ◽  
Bharathi Avula ◽  
...  
Keyword(s):  
Triamcinolone Acetonide ◽  
Polymer Matrix ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Invasive Technique ◽  
Content Uniformity ◽  
Scanning Calorimetry ◽  
Ocular Tissues

Delivering an effective drug load to the posterior section of the ocular tissues, while using a non-invasive technique, has always been a challenge. In this regard, the goal of the present study was to develop sustained release triamcinolone acetonide (TA) loaded polymeric matrix films for ocular delivery. The TA-films were prepared in two different polymer matrices, with drug loadings of 10% and 20% w/w, and they were evaluated for ocular distribution in vivo in a conscious rabbit model. A 4% w/v TA suspension (TA-C) was used as a control for in vitro and in vivo studies. The TA-films, prepared with melt-cast technology, used polyethylene oxide (PEO) and Soluplus® as the polymer matrix. The films were evaluated with respect to assay, content uniformity, excipient interaction, and permeability across isolated rabbit sclera. The distribution of TA in the ocular tissues, post topical administration, was determined in New Zealand male albino rabbits as a function of dose, and was compared against TA-C. The assay of the 10% and 20% w/w film was in the range from 70–79% and 92–94% for the Soluplus® and PEO films, respectively, and content uniformity was in the range of 95–103% for both the films. The assay of the TA from Soluplus® films was less compared with the PEO films and showed an interaction with TA, as revealed by Differential Scanning Calorimetry (DSC). Hence, Soluplus® films were not selected for further studies. No interaction was observed between the drug and PEO polymer matrix. The enhancement of trans-scleral flux and permeability of TA was about 1.16 and 1.33-folds, respectively, from the 10% w/w PEO and 3.5 and 2.12-folds, respectively, from the 20% w/w PEO films, as compared with TA-C formulations. The in vivo studies demonstrate that significantly higher TA levels were observed in the anterior and posterior segments of the eye at the end of 6h with the PEO films. Therefore, the PEO based polymeric films were able to deliver TA into the back of the eye efficiently and for prolonged periods.

scholarly journals Effects of Tedizolid Phosphate on Survival Outcomes and Suppression of Production of Staphylococcal Toxins in a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Vien T. M. Le ◽  
Hoan N. Le ◽  
Marcos Gabriel Pinheiro ◽  
Kenneth J. Hahn ◽  
Mary L. Dinh ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Production ◽  
Protective Efficacy ◽  
Survival Rates ◽  
Rabbit Model ◽  
Rank Test ◽  
Necrotizing Pneumonia ◽  
Time Curve ◽  
Content Type

ABSTRACT The protective efficacy of tedizolid phosphate, a novel oxazolidinone that potently inhibits bacterial protein synthesis, was compared to those of linezolid, vancomycin, and saline in a rabbit model of Staphylococcus aureus necrotizing pneumonia. Tedizolid phosphate was administered to rabbits at 6 mg/kg of body weight intravenously twice daily, which yielded values of the 24-h area under the concentration-time curve approximating those found in humans. The overall survival rate was 83% for rabbits treated with 6 mg/kg tedizolid phosphate twice daily and 83% for those treated with 50 mg/kg linezolid thrice daily (P = 0.66 by the log-rank test versus the results obtained with tedizolid phosphate). These survival rates were significantly greater than the survival rates of 17% for rabbits treated with 30 mg/kg vancomycin twice daily (P = 0.003) and 17% for rabbits treated with saline (P = 0.002). The bacterial count in the lungs of rabbits treated with tedizolid phosphate was significantly decreased compared to that in the lungs of rabbits treated with saline, although it was not significantly different from that in the lungs of rabbits treated with vancomycin or linezolid. The in vivo bacterial production of alpha-toxin and Panton-Valentine leukocidin, two key S. aureus-secreted toxins that play critical roles in the pathogenesis of necrotizing pneumonia, in the lungs of rabbits treated with tedizolid phosphate and linezolid was significantly inhibited compared to that in the lungs of rabbits treated with vancomycin or saline. Taken together, these results indicate that tedizolid phosphate is superior to vancomycin for the treatment of S. aureus necrotizing pneumonia because it inhibits the bacterial production of lung-damaging toxins at the site of infection.

Cefotaxime and amikacin: results of in vitro and in vivo studies against Gram-negative bacteria and Staphylococcus aureus

1980 ◽  
Vol 6 (suppl A) ◽  
pp. 55-61 ◽  
Author(s):  
J. Klastersky ◽  
H. Gaya ◽  
S. H. Zinner ◽  
C. Bernard ◽  
J-C. Ryff ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
In Vivo Studies ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
And Staphylococcus Aureus

scholarly journals Impact of the Order of Initiation of Fluconazole and Amphotericin B in Sequential or Combination Therapy on Killing of Candida albicans In Vitro and in a Rabbit Model of Endocarditis and Pyelonephritis

2001 ◽  
Vol 45 (2) ◽  
pp. 485-494 ◽  
Author(s):  
Arnold Louie ◽  
Pamela Kaw ◽  
Partha Banerjee ◽  
Weiguo Liu ◽  
George Chen ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Amphotericin B ◽  
Induced Resistance ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Infection Model ◽  
Simultaneous Exposure ◽  
The Impact

ABSTRACT In vitro time-kill studies and a rabbit model of endocarditis and pyelonephritis were used to define the impact that the order of exposure of Candida albicans to fluconazole (FLC) and amphotericin B (AMB), as sequential and combination therapies, had on the susceptibility of C. albicans to AMB and on the outcome. The contribution of FLC-induced resistance to AMB for C. albicans also was assessed. In vitro, AMB monotherapy rapidly killed each of four C. albicans strains; FLC alone was fungistatic. Preincubation of these fungi with FLC for 18 h prior to exposure to AMB decreased their susceptibilities to AMB for 8 to >40 h. Induced resistance to AMB was transient, but the duration of resistance increased with the length of FLC preincubation. Yeast sequentially incubated with FLC followed by AMB plus FLC (FLC→AMB+FLC) showed fungistatic growth kinetics similar to that of fungi that were exposed to FLC alone. This antagonistic effect persisted for at least 24 h. Simultaneous exposure of C. albicans to AMB and FLC [AMB+FLC(simult)] demonstrated activity similar to that with AMB alone for AMB concentrations of ≥1 μg/ml; antagonism was seen using an AMB concentration of 0.5 μg/ml. The in vitro findings accurately predicted outcomes in our rabbit infection model. In vivo, AMB monotherapy and treatment with AMB for 24 h followed by AMB plus FLC (AMB→AMB+FLC) rapidly sterilized kidneys and cardiac vegetations. AMB+FLC(simult) and FLC→AMB treatments were slower in clearing fungi from infected tissues. FLC monotherapy and FLC→AMB+FLC were both fungistatic and were the least active regimens. No adverse interaction was observed between AMB and FLC for the AMB→FLC regimen. However, FLC→AMB treatment was slower than AMB alone in clearing fungi from tissues. Thus, our in vitro and in vivo studies both demonstrate that preexposure of C. albicans to FLC reduces fungal susceptibility to AMB. The length of FLC preexposure and whether AMB is subsequently used alone or in combination with FLC determine the duration of induced resistance to AMB.

scholarly journals Characterization and Antibiofilm Activity of Mannitol–Chitosan-Blended Paste for Local Antibiotic Delivery System

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 517 ◽  
Author(s):  
Leslie R. Pace ◽  
Zoe L. Harrison ◽  
Madison N. Brown ◽  
Warren O. Haggard ◽  
J. Amber Jennings
Keyword(s):  
Infection Prevention ◽  
Bacterial Biofilm ◽  
Antibiofilm Activity ◽  
Persister Cells ◽  
In Vivo Evaluation ◽  
Musculoskeletal Infection ◽  
Prevention And Treatment ◽  
Local Antibiotic ◽  
Antibiotic Delivery

Mannitol, a polyalcohol bacterial metabolite, has been shown to activate dormant persister cells within bacterial biofilm. This study sought to evaluate an injectable blend of mannitol, chitosan, and polyethylene glycol for delivery of antibiotics and mannitol for eradication of Staphylococcal biofilm. Mannitol blends were injectable and had decreased dissociation and degradation in the enzyme lysozyme compared to blends without mannitol. Vancomycin and amikacin eluted in a burst response, with active concentrations extended to seven days compared to five days for blends without mannitol. Mannitol eluted from the paste in a burst the first day and continued through Day 4. Eluates from the mannitol pastes with and without antibiotics decreased viability of established S. aureus biofilm by up to 95.5% compared to blends without mannitol, which only decreased biofilm when loaded with antibiotics. Cytocompatibility tests indicated no adverse effects on viability of fibroblasts. In vivo evaluation of inflammatory response revealed mannitol blends scored within the 2–4 range at Week 1 (2.6 ± 1.1) and at Week 4 (3.0 ± 0.8), indicative of moderate inflammation and comparable to non-mannitol pastes (p = 0.065). Clinically, this paste could be loaded with clinician-selected antibiotics and used as an adjunctive therapy for musculoskeletal infection prevention and treatment.

scholarly journals Rabbit model of Staphylococcus aureus implant-associated spinal infection

2020 ◽  
Vol 13 (7) ◽  
pp. dmm045385
Author(s):  
Oren Gordon ◽  
Robert J. Miller ◽  
John M. Thompson ◽  
Alvaro A. Ordonez ◽  
Mariah H. Klunk ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Remodeling ◽  
Ex Vivo ◽  
Rabbit Model ◽  
Pedicle Screws ◽  
Lumbar Vertebra ◽  
Wound Dehiscence ◽  
Spinal Infection ◽  
Positron Emission

ABSTRACTPost-surgical implant-associated spinal infection is a devastating complication commonly caused by Staphylococcus aureus. Biofilm formation is thought to reduce penetration of antibiotics and immune cells, contributing to chronic and difficult-to-treat infections. A rabbit model of a posterior-approach spinal surgery was created, in which bilateral titanium pedicle screws were interconnected by a plate at the level of lumbar vertebra L6 and inoculated with a methicillin-resistant S.aureus (MRSA) bioluminescent strain. In vivo whole-animal bioluminescence imaging (BLI) and ex vivo bacterial cultures demonstrated a peak in bacterial burden by day 14, when wound dehiscence occurred. Structures suggestive of biofilm, visualized by scanning electron microscopy, were evident up to 56 days following infection. Infection-induced inflammation and bone remodeling were also monitored using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and computed tomography (CT). PET imaging signals were noted in the soft tissue and bone surrounding the implanted materials. CT imaging demonstrated marked bone remodeling and a decrease in dense bone at the infection sites. This rabbit model of implant-associated spinal infection provides a valuable preclinical in vivo approach to investigate the pathogenesis of implant-associated spinal infections and to evaluate novel therapeutics.

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