scholarly journals An Antibiotic-Releasing Bone Void Filling (ABVF) Putty for the Treatment of Osteomyelitis

Materials ◽  
2020 ◽  
Vol 13 (22) ◽  
pp. 5080
Author(s):  
Raquib Hasan ◽  
Abbey Wohlers ◽  
Jacob Shreffler ◽  
Pranothi Mulinti ◽  
Hunter Ostlie ◽  
...  
Keyword(s):  
Bone Growth ◽  
Release Kinetics ◽  
Control Group ◽  
Joint Replacements ◽  
Total Joint Replacements ◽  
Press Fitting ◽  
Antibiotic Release ◽  
Bone Void

The number of total joint replacements (TJR) is on the rise with a corresponding increase in the number of infected TJR, which necessitates revision surgeries. Current treatments with either non-biodegradable, antibiotic-releasing polymethylmethacrylate (PMMA) based bone cement, or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection. Here, we report a biodegradable, easy-to-use “press-fitting” antibiotic-releasing bone void filling (ABVF) putty that not only provides efficient antibiotic release kinetics at the site of infection but also allows efficient osseointegration. The ABVF formulation was prepared using poly (D,L-lactide-co-glycolide) (PLGA), polyethylene glycol (PEG), and polycaprolactone (PCL) as the polymer matrix, antibiotic vancomycin, and osseointegrating synthetic bone PRO OSTEON for bone-growth support. ABVF was homogenous, had a porous structure, was moldable, and showed putty-like mechanical properties. The ABVF putty released vancomycin for 6 weeks at therapeutic level. Furthermore, the released vancomycin showed in vitro antibacterial activity against Staphylococcus aureus for 6 weeks. Vancomycin was not toxic to osteoblasts. Finally, ABVF was biodegradable in vivo and showed an effective infection control with the treatment group showing significantly higher bone growth (p < 0.001) compared to the control group. The potential of infection treatment and osseointegration makes the ABVF putty a promising treatment option for osteomyelitis after TJR.

scholarly journals Extended Release Combination Antibiotic Therapy from a Bone Void Filling Putty for Treatment of Osteomyelitis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 592
Author(s):  
Hasan ◽  
Schaner ◽  
Schroeder ◽  
Wohlers ◽  
Shreffler ◽  
...  
Keyword(s):  
Bone Growth ◽  
Release Kinetics ◽  
Causative Factor ◽  
Infection Model ◽  
Antibiofilm Activity ◽  
Surgical Interventions ◽  
Bone Void ◽  
Biofilm Infection

In spite of advances in Total Joint Replacements (TJR), infection remains a major concern and a primary causative factor for revision surgery. Current clinical standards treat these osteomyelitis infections with antibiotic-laden poly(methyl methacrylate) (PMMA)-based cement, which has several disadvantages, including inadequate local drug release kinetics, antibiotic leaching for a prolonged period and additional surgical interventions to remove it, etc. Moreover, not all antibiotics (e.g., rifampicin, a potent antibiofilm antibiotic) are compatible with PMMA. For this reason, treatment of TJR-associated infections and related complications remains a significant concern. The objective of this study was to develop a polymer-controlled dual antibiotic-releasing bone void filler (ABVF) with an underlying osseointegrating substrate to treat TJR implant-associated biofilm infections. An ABVF putty was designed to provide sustained vancomycin and rifampicin antibiotic release for 6 weeks while concurrently providing an osseointegrating support for regrowth of lost bone. The reported ABVF showed efficient antibacterial and antibiofilm activity both in vitro and in a rat infection model where the ABVF both showed complete bacterial elimination and supported bone growth. Furthermore, in an in vivo k-wire-based biofilm infection model, the ABVF putty was also able to eliminate the biofilm infection while supporting osseointegration. The retrieved k-wire implants were also free from biofilm and bacterial burden. The ABVF putty delivering combination antibiotics demonstrated that it can be a viable treatment option for implant-related osteomyelitis and may lead to retention of the hardware while enabling single-stage surgery.

Bone-Bonding Ability of Ce-TZP/Al2O3 Nanocomposite with a Microporous Surface and Calcium Phosphate Coating

2005 ◽  
Vol 284-286 ◽  
pp. 987-990 ◽  
Author(s):  
Mitsuru Takemoto ◽  
Shunsuke Fujibayashi ◽  
J. Suzuki ◽  
Tadashi Kokubo ◽  
Takashi Nakamura
Keyword(s):  
Calcium Phosphate ◽  
Tetragonal Zirconia ◽  
Calcium Phosphate Coating ◽  
Control Group ◽  
Phosphate Coating ◽  
Joint Replacements ◽  
Total Joint Replacements ◽  
Al2o3 Composite ◽  
High Bone

The nano-composite of a ceria-stabilized tetragonal zirconia polycrystals (Ce-TZP) and alumina (Al2O3) polycrystals (Ce-TZP/Al2O3) is attractive as a load-bearing bone substitute because of its mechanical properties and phase stability. We have developed a new method of hydrofluoric acid and heat treatment (HFT) to give a microporous structure to the surface of this Ce-TZP/Al2O3 nanocomposite ceramic. Bone-bonding ability of a microporous surface and calcium phosphate coating on Ce-TZP/Al2O3 composite has been investigated through in vivo detaching model. Thin calcium phosphate coating layer was added by alternate soaking process, and thick CaP layer was produced by soaking in simulated body fluid for 5 days. HFT treated Ce-TZP/Al2O3 composite showed high bone-bonding ability compared with the control group. Thick and thin CaP coating accelerated bone-bonding ability in early post-implantation period. The submicron microporous surface was beneficial for achieving mechanical interlocking between the ceramic and surrounding bone. These results suggest the possibility of using a Ce-TZP/Al2O3 nanocomposite ceramic with microporous surface and calcium phosphate coating as the bearing material for uncemented total joint replacements.

scholarly journals Electrospun, synthetic bone void filler promotes human MSC function and BMP-2 mediated spinal fusion

2020 ◽  
Vol 35 (4-5) ◽  
pp. 532-543
Author(s):  
Juliane D Glaeser ◽  
Khosrowdad Salehi ◽  
Linda EA Kanim ◽  
Derek G Ju ◽  
Jae Hyuk Yang ◽  
...  
Keyword(s):  
Spinal Fusion ◽  
Release Kinetics ◽  
Micro Ct ◽  
Synthetic Bone ◽  
Group I ◽  
Bone Void Filler ◽  
Group Ii ◽  
Bone Void

Introduction Synthetic bone grafts are often used to achieve a well-consolidated fusion mass in spinal fusion procedures. These bone grafts function as scaffolds, and ideally support cell function and facilitate protein binding. Objective The aim was to characterize an electrospun, synthetic bone void filler (Reb) for its bone morphogenetic protein (BMP)-2 release properties and support of human mesenchymal stem cell (hMSC) function in vitro, and its efficacy in promoting BMP-2-/bone marrow aspirate-(BMA)-mediated posterolateral spinal fusion (PLF) in vivo. Methods BMP-2 release kinetics from Reb versus standard absorbable collagen sponge (ACS) was determined. hMSC adhesion and proliferation on Reb was tested using cell counting, fluorescence microscopy and MTS. Cell osteogenic differentiation was quantified via cellular alkaline phosphatase (ALP) activity. For in vivo analysis, 18 Lewis rats were treated during PLF surgery with the following groups: (I) Reb + BMA, (II) Reb + BMA + BMP-2 and (III) BMA. A safe, minimally effective dose of BMP-2 was used. Fusion consolidation was followed for 3 months using radiography and micro-CT. After sacrifice, fusion rate and biomechanical stiffness was determined using manual palpation, biomechanical tests and histology. Results In vitro, BMP-2 release kinetics were similar between Reb versus ACS. MSC proliferation and differentiation were increased in the presence of Reb. At 3 months post-surgery, fusion rates were 29% (group I), 100% (group II), and 0% (group III). Biomechanical stiffness was higher in group II versus I. Micro-CT showed an increased bone volume and connectivity density in group II. Trabecular thickness was increased in group I versus II. H&E staining showed newly formed bone in group II only. Conclusions Reb possesses a high protein binding affinity and promotes hMSC function. Combination with BMA and minimal dose BMP-2 allowed for 100% bone fusion in vivo. This data suggests that a minimally effective dose of BMP-2 can be used when combined with Reb.

scholarly journals Evaluation of Polyacrylonitrile Nonwoven Mats and Silver–Gold Bimetallic Nanoparticle-Decorated Nonwoven Mats for Potential Promotion of Wound Healing In Vitro and In Vivo and Bone Growth In Vitro

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 516
Author(s):  
Meng-Yi Bai ◽  
Fang-Yu Ku ◽  
Jia-Fwu Shyu ◽  
Tomohiro Hayashi ◽  
Chia-Chun Wu
Keyword(s):  
Wound Healing ◽  
Bone Growth ◽  
Skin Tissue ◽  
Control Group ◽  
Ag Nanoparticle ◽  
Bimetallic Nanoparticle ◽  
In Vivo Animal Model ◽  
Nonwoven Mats

We prepared polyacrylonitrile (PAN) and urchin-like Ag–Au bimetallic or Ag nanoparticle-decorated PAN nonwoven mats using electrospinning and evaluated them in vitro and in vivo for wound healing, antibacterial effects on skin tissue, and promotion of bone ingrowth in vitro. A facile, green, low-temperature protocol was developed to obtain these nonwoven mats. The sterilization rate of urchin-like Ag–Au bimetallic and Ag nanoparticle-decorated PAN nonwoven mats against Staphylococcus aureus was 96.81 ± 2.81% and 51.90 ± 9.07%, respectively, after 5 h treatment. In an in vitro cell model, these two mats did not show significant toxicity; cell viability of >80% was obtained within 5 h of treatment. In vivo animal model preclinical assessment showed that the urchin-like Ag–Au bimetallic nonwoven mat group showed significant wound recovery because of sebaceous gland, hair follicle, and fat formation during skin tissue regeneration; increased neovascularization and compact collagen fibers were observed in the dermal layer, comparable to the findings for the control group. The mother substrate of the urchin-like Ag–Au bimetallic nanoparticle-decorated PAN nonwoven mats, that is, pure PAN nonwoven mats, was found to be a potential scaffold for bone tissue engineering as osteoblast ingrowth from the top to the bottom of the membrane and proliferation inside the membrane were observed. The key genetic factor Cbfa1 was identified as a key osteoblast differentiation regulator in vitro. Thus, electrospun membrane materials show potential for use as dual-functional biomaterials for bone regeneration and infection control and composite grafts for infectious bone and soft tissue defects.

scholarly journals Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 26
Author(s):  
Victoria Wall ◽  
Thi-Hiep Nguyen ◽  
Nghi Nguyen ◽  
Phong A. Tran
Keyword(s):  
Bone Cement ◽  
Joint Infections ◽  
Current State ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Bone Void

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

Utilizing ICG Spectroscopical Properties for Real-Time Nanoparticle Release Quantification In vitro and In vivo in Imaging Setups

2020 ◽  
Vol 26 (31) ◽  
pp. 3828-3833 ◽  
Author(s):  
Tuula Peñate-Medina ◽  
Eike Kraas ◽  
Kunliang Luo ◽  
Jana Humbert ◽  
Hanwen Zhu ◽  
...  
Keyword(s):  
Release Kinetics ◽  
Pure Water ◽  
Squamous Carcinoma ◽  
Peak Shift ◽  
Intensity Increase ◽  
Nude Mouse Model ◽  
Absorption And Emission ◽  
Squamous Carcinoma Cells

Background: Nanoparticle imaging and tracking the release of the loaded material from the nanoparticle system have attracted significant attention in recent years. If the release of the loaded molecules could be monitored reliably in vivo, it would speed up the development of drug delivery systems remarkably. Methods: Here, we test a system that uses indocyanine green (ICG) as a fluorescent agent for studying release kinetics in vitro and in vivo from the lipid iron nanoparticle delivery system. The ICG spectral properties like its concentration dependence, sensitivity and the fluctuation of the absorption and emission wavelengths can be utilized for gathering information about the change of the ICG surrounding. Results: We have found that the absorption, fluorescence, and photoacoustic spectra of ICG in lipid iron nanoparticles differ from the spectra of ICG in pure water and plasma. We followed the ICG containing liposomal nanoparticle uptake into squamous carcinoma cells (SCC) by fluorescence microscopy and the in vivo uptake into SCC tumors in an orthotopic xenograft nude mouse model under a surgical microscope. Conclusion: Absorption and emission properties of ICG in the different solvent environment, like in plasma and human serum albumin, differ from those in aqueous solution. Photoacoustic spectral imaging confirmed a peak shift towards longer wavelengths and an intensity increase of ICG when bound to the lipids. The SCC cells showed that the ICG containing liposomes bind to the cell surface but are not internalized in the SCC-9 cells after 60 minutes of incubation. We also showed here that ICG containing liposomal nanoparticles can be traced under a surgical camera in vivo in orthotopic SCC xenografts in mice.

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

Agitation Techniques to Enhance Drainage of Retained Hemothorax

2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  
Keyword(s):  
Trauma Surgery ◽  
Control Group ◽  
In Vivo Experiments ◽  
Vibration Technique ◽  
Retained Hemothorax ◽  
And Control ◽  
Negative Conclusion ◽  
Benchtop Model

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.

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