scholarly journals Silica-Polymer Composites as the Novel Antibiotic Delivery Systems for Bone Tissue Infection

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 28 ◽  
Author(s):  
Adrianna Skwira ◽  
Adrian Szewczyk ◽  
Agnieszka Konopacka ◽  
Monika Górska ◽  
Dorota Majda ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Staphylococcus Aureus ◽  
Bone Tissue ◽  
Delivery Systems ◽  
Human Osteoblasts ◽  
X Ray ◽  
Freeze Dried ◽  
Mcm 41 ◽  
Antibiotic Delivery

Bone tissue inflammation, osteomyelitis, is commonly caused by bacterial invasion and requires prolonged antibiotic therapy for weeks or months. Thus, the aim of this study was to develop novel silica-polymer local bone antibiotic delivery systems characterized by a sustained release of ciprofloxacin (CIP) which remain active against Staphylococcus aureus for a few weeks, and do not have a toxic effect towards human osteoblasts. Four formulations composed of ethylcellulose (EC), polydimethylsiloxane (PDMS), freeze-dried CIP, and CIP-adsorbed mesoporous silica materials (MCM-41-CIP) were prepared via solvent-evaporation blending method. All obtained composites were characterized in terms of molecular structure, morphological, and structural properties by using Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy (SEM/EDX), and X-ray diffraction (XRD), thermal stability by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), and in vitro antibiotic release. The antibacterial activity against Staphylococcus aureus (ATCC 6538) as well as the in vitro cytocompatibility to human osteoblasts of obtained composites were also examined. Physicochemical results confirmed the presence of particular components (FTIR), formation of continuous polymer phase onto the surface of freeze-dried CIP or MCM-41-CIP (SEM/EDX), and semi-crystalline (composites containing freeze-dried CIP) or amorphous (composites containing MCM-41-CIP) structure (XRD). TGA and DSC analysis indicated the high thermal stability of CIP adsorbed onto the MCM-41, and higher after MCM-41-CIP coating with polymer blend. The release study revealed the significant reduction in initial burst of CIP for the composites which contained MCM-41-CIP instead of freeze-dried CIP. These composites were also characterized by the 30-day activity against S. aureus and the highest cytocompatibility to human osteoblasts in vitro.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

Fabrication and characterization of novel ethyl cellulose-grafted-poly (ɛ-caprolactone)/alginate nanofibrous/macroporous scaffolds incorporated with nano-hydroxyapatite for bone tissue engineering

2019 ◽  
Vol 33 (8) ◽  
pp. 1128-1144 ◽  
Author(s):  
Vahideh Raeisdasteh Hokmabad ◽  
Soodabeh Davaran ◽  
Marziyeh Aghazadeh ◽  
Reza Rahbarghazi ◽  
Roya Salehi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Ethyl Cellulose ◽  
Three Dimensional ◽  
Drying Methods ◽  
Layer By Layer ◽  
Freeze Dried ◽  
Proliferation And Differentiation

The major challenge of tissue regeneration is to develop three dimensional scaffolds with suitable properties which would mimic the natural extracellular matrix to induce the adhesion, proliferation, and differentiation of cells. Several materials have been used for the preparation of the scaffolds for bone regeneration. In this study, novel ethyl cellulose-grafted-poly (ɛ-caprolactone) (EC-g-PCL)/alginate scaffolds with different contents of nano-hydroxyapatite were prepared by combining electrospinning and freeze-drying methods in order to provide nanofibrous/macroporous structures with good mechanical properties. For this aim, EC-g-PCL nanofibers were obtained with electrospinning, embedded layer-by-layer in alginate solutions containing nano-hydroxyapatite particles, and finally, these constructions were freeze-dried. The scaffolds possess highly porous structures with interconnected pore network. The swelling, porosity, and degradation characteristics of the EC-g-PCL/alginate scaffolds were decreased with the increase in nano-hydroxyapatite contents, whereas increases in the in-vitro biomineralization and mechanical strength were observed as the nano-hydroxyapatite content was increased. The cell response to EC-g-PCL/alginate scaffolds with/or without nano-hydroxyapatite was investigated using human dental pulp stem cells (hDPSCs). hDPSCs displayed a high adhesion, proliferation, and differentiation on nano-hydroxyapatite-incorporated EC-g-PCL/alginate scaffolds compared to pristine EC-g-PCL/alginate scaffold. Overall, these results suggested that the EC-g-PCL/alginate-HA scaffolds might have potential applications in bone tissue engineering.

Bioactive Composite Materials for Bone Tissue Applications

2006 ◽  
Vol 514-516 ◽  
pp. 985-989
Author(s):  
B.J.M. Leite Ferreira ◽  
M.G.G.M. Duarte ◽  
M. Helena Gil ◽  
Rui N. Correia ◽  
J. Román ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Bone Tissue ◽  
Tissue Repair ◽  
Body Fluid ◽  
In Vitro Bioactivity ◽  
X Ray Diffraction ◽  
X Ray ◽  
Biodegradable Composite ◽  
Scanning Electron

Two materials with potential application in bone tissue repair have been developed: 1) a non-biodegradable composite based in a new methacrylic-co-acrylic matrix; and 2) a biodegradable composite based in a chitosan (Ch) matrix. Both matrices were reinforced with glass-ceramic particles of composition (mol%) 70 SiO2 – 30 CaO. The in vitro bioactivity of composites was assessed by soaking in simulated body fluid (SBF) for periods of up to 7 days at 37º C. X-ray diffraction (XRD) and scanning electron microscopy coupled with X-ray energy dispersive spectroscopy (SEM-EDS) were used for deposit identification after different soaking periods. Calcium phosphate particulate deposits were detected after 3 days of immersion, followed by growth and maturation towards apatite.

scholarly journals Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm

2016 ◽  
Vol 60 (10) ◽  
pp. 5688-5694 ◽  
Author(s):  
Daniel G. Meeker ◽  
Karen E. Beenken ◽  
Weston B. Mills ◽  
Allister J. Loughran ◽  
Horace J. Spencer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Limit Of Detection ◽  
Relative Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Comparable Activity ◽  
Antibiotic Delivery

ABSTRACTWe usedin vitroandin vivomodels of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistantStaphylococcus aureus(MRSA) in the specific context of an established biofilm. The results demonstrated that, underin vitroconditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when testedin vivoin a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associatedS. aureusinfections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.

In vitro effectiveness of 455-nm blue LED to reduce the load of Staphylococcus aureus and Candida albicans biofilms in compact bone tissue

2015 ◽  
Vol 31 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Luciano Pereira Rosa ◽  
Francine Cristina da Silva ◽  
Magda Souza Viana ◽  
Giselle Andrade Meira
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Bone Tissue ◽  
Compact Bone ◽  
Compact Bone Tissue ◽  
Blue Led ◽  
Candida Albicans Biofilms

scholarly journals Experimental substantiation of osteotransplant application in traumatic vertebral defects

2018 ◽  
Vol 15 (4) ◽  
pp. 41-51
Author(s):  
V. V. Rerikh ◽  
Yu. A. Predein ◽  
A. M. Zaidman ◽  
A. D. Lastevsky ◽  
V.A. Bataev V.A. Bataev V.A. Bataev ◽  
...  
Keyword(s):  
Bone Graft ◽  
Bone Tissue ◽  
Vertebral Body ◽  
Morphological Structure ◽  
Allogeneic Bone ◽  
X Ray ◽  
Organ Specific ◽  
Ray Density ◽  
Vertebral Defects

Objective. To analyze the features of bone tissue formation during plasty of vertebral body defect or fracture with an allogeneic bone graft in an experiment in vitro. Material and Methods. Models of the vertebral body defect (fracture of the cranioventral part with penetration into the nucleus pulposus) were created in an experiment on 20 mini-pigs of the same age. Plasty of traumatic defects was performed with allogeneic bone graft or autologous bone. CT, histological, and spectrometric studies of microscopic specimens were carried out at 14, 30, 90, and 180 day. Reparative osteogenesis, X-ray density, Ca and P content, and microhardness were studied. Results. After implantation of allogeneic bone graft, an organ-specific bone similar to the recipient’s bone in morphological structure, X-ray density, mineral composition and microhardness, was formed on the 90th day (P = 0.01). After transplantation of autobone, the regenerate formed by this day in the central part was in a phase of resorption and restructuring with lower indices of X-ray density, content of Ca and P, and microhardness (P = 0.01). Conclusion. Аfter plasty of vertebral body traumatic defects with allogeneic bone graft, the organ-specific bone tissue is formed at an earlier time and reliably exhibits greater mineralization and strength.

scholarly journals A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss

2021 ◽  
Vol 9 ◽  
Author(s):  
Cong Yao ◽  
Meisong Zhu ◽  
Xiuguo Han ◽  
Qiang Xu ◽  
Min Dai ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Loss ◽  
Bone Tissue ◽  
Mesoporous Silica Nanoparticles ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Bacterial Biofilm ◽  
Orthopaedic Implant

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.

scholarly journals Staphylococcus aureus infects osteoclasts and replicates intracellularly

2019 ◽  
Author(s):  
Jennifer L Krauss ◽  
Philip M Roper ◽  
Anna Ballard ◽  
Chien-Cheng Shih ◽  
James AJ Fitzpatrick ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Confocal Microscopy ◽  
Bone Tissue ◽  
Post Infection ◽  
Bone Structure ◽  
High Rate ◽  
Therapeutic Interventions ◽  
Intracellular Infection

AbstractOsteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. The majority of OM is caused by Staphylococcus aureus, and even with proper treatment, OM has a high rate of recurrence and chronicity. While S. aureus has been shown to infect osteoblasts, persist intracellularly, and promote the release of pro-osteoclastogenic cytokines, it remains unclear whether osteoclasts (OCs) are also a target of intracellular infection. In this study, we examined the interaction between S. aureus and OCs, demonstrating internalization of GFP-labeled bacteria by confocal microscopy, both in vitro and in vivo. Utilizing an intracellular survival assay and flow cytometry during OC differentiation from bone marrow macrophages (BMMs), we found that the intracellular burden of S. aureus increases after initial infection in cells with at least 2 days of exposure to the osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL). Presence of dividing bacteria was confirmed via visualization by transmission electron microscopy. In contrast, undifferentiated BMMs, or those treated with interferon-γ or IL-4, had fewer internal bacteria, or no change, respectively, at 18 hours post infection, compared to 1.5 hours post infection. To further explore the signals downstream of RANKL, we manipulated NFATc1 and alternative NF-κB, which controls NFATc1 and other factors affecting OC function, finding that intracellular bacterial growth correlates with NFATc1 levels in RANKL-treated cells. Confocal microscopy in mature OCs showed a range of intracellular infection that correlated inversely with S. aureus and phagolysosome colocalization. The ability of OCs to become infected, paired with their diminished bactericidal capacity compared to BMMs, could promote OM progression by allowing S. aureus to evade initial immune regulation and proliferate at the periphery of lesions where OCs and bone remodeling are most abundant.Author SummaryThe inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium Staphylococcus aureus. To date, the bone building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone resorbing cells, osteoclasts, participate. In this study, we show that S. aureus can infect osteoclasts and proliferate inside these cells, whereas macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system. Therapeutic interventions that target osteoclasts specifically might reduce the severity of OM or improve antibiotic responses.

Stability of the Magnesium Carbonate Apatite/Anionic Collagen Scaffolds: Effect of the Cross-Link Concentration

2011 ◽  
Vol 493-494 ◽  
pp. 844-848 ◽  
Author(s):  
Marcia S. Sader ◽  
Gutemberg Alves ◽  
Racquel Z. LeGeros ◽  
Gloria Dulce de Almeida Soares
Keyword(s):  
Bone Tissue ◽  
Culture Medium ◽  
Type I Collagen ◽  
Type I ◽  
Carbonate Apatite ◽  
Reaction Products ◽  
Collagen Scaffolds ◽  
Freeze Dried ◽  
The Cross

Natural bone constitutes of an inorganic phase (a biological nanoapatite) and an organic phase (mostly type I collagen). The challenge is to develop a material that can regenerate lost bone tissue with degradation and resorption kinetics compatible with the new bone formation. The aim of this study was to prepare self-organized magnesium and carbonate substituted apatite/collagen scaffolds, cross-linked with glutaraldehyde (GA). Bovine tendon was submitted to alkaline treatment resulting in a negatively charged collagen surface. The scaffolds were prepared by precipitation: simultaneous dropwise addition of solution containing calcium (Ca) and magnesium (Mg) ions and collagen into a buffered solution containing carbonate and phosphate ions in reaction vessel maintained at 37 °C, pH=8. The reaction products were cross-linked with 0.125 and 0.25% (v/v) glutaraldehyde (GA) solution and freeze-dried. The samples were characterized by Fourier-transformed infrared spectroscopy (FTIR). In vitro cytotoxicity (based on three parameters assays) and scaffolds degradation in culture medium and osteoblastic cells culture were performed in the cross-linked materials. No cytotoxic effects were observed. The cross-linked samples with the lower GA concentration showed a lower stability when placed in contact with culture medium. Human osteoblasts attached on the scaffolds surface cross-linked with 0.25% GA, forming a continuous layer after 14 days of incubation. These results showed potential application of the designed scaffolds for bone tissue engineering.

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