Effect of Metal Substrate Nanometer Topography on Osteoblast Metabolic Activities

2004 ◽  
Vol 823 ◽  
Author(s):  
Brian C. Ward ◽  
Thomas J. Webster
Keyword(s):  
Metal Surfaces ◽  
Orthopedic Implants ◽  
Metal Substrate ◽  
Implant Failure ◽  
Orthopedic Implant ◽  
Energy Dispersion Spectroscopy ◽  
Metal Substrates ◽  
Cell Functions ◽  
Metabolic Activities

AbstractSurgeons and bioengineers have continuously been challenged by implant failure. Many of these engineers and surgeons trace implant failure to poor osseointegration (the bonding of an orthopedic implant to juxtaposed bone) and to the inability of implants to match the physical properties of surrounding bone. Researchers have recently shown that nanostructured materials (or materials with fundamental length scales less than 100 nm) enhance cell functions pertinent to effectively regenerating the tissue of numerous organs. Specifically, in a recent study, researchers demonstrated that metal surfaces utilizing low-micron to nanophase topography fostered increased adhesion of osteoblasts, the cells that create the matrix of bone. In this study, Ti, Ti6Al4V, and CoCrMo alloys were investigated, and these alloys were identical to current orthopedic implant alloys except for surface topography. The objective of this in vitro research was to determine whether these same nanophase metal surfaces not only foster osteoblast adhesion but also increase osteoblast metabolic activities leading to bone regeneration. Light microscopy and Energy Dispersion Spectroscopy (EDS) were used to verify the presence of calcium and phosphorous deposition by osteoblasts cultured on the metal substrates. Results indicated that both calcium and phosphorous are being deposited on several of the metal substrates. More importantly, compared to conventional metals, results provided the first evidence that more calcium and phosphorous was deposited by osteoblasts cultured on respective nanophase metals (Ti, Ti6Al4V, and CoCrMo). Nanophase CoCrMo had the most calcium and phosphorous minerals deposited by osteoblasts compared to any other metal substrate. Thus, the results of this study continue to provide evidence for the use of nanophase metals for the design of the next generation of more successful orthopedic implants.

scholarly journals Antibacterial and Anti-Inflammatory Coating Materials for Orthopedic Implants: A Review

Coatings ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1401
Author(s):  
Gang Tan ◽  
Jing Xu ◽  
Walter Munesu Chirume ◽  
Jieyu Zhang ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Hot Spot ◽  
Orthopedic Implants ◽  
Implant Failure ◽  
Social Benefits ◽  
Orthopedic Implant ◽  
Common Complication ◽  
Coating Materials ◽  
Implant Infection ◽  
Implant Coating ◽  
Anti Inflammatory

Orthopedic implant failure is the most common complication of orthopedic surgery, causing serious trauma and resulting in a tremendous economic burden for patients. There are many reasons for implant failure, among which peri-implant infection (or implant-related infection) and aseptic loosening are the most important. At present, orthopedic doctors have many methods to treat these complications, such as revision surgery, which have shown good results. However, if peri-implant infection can be prevented, this will bring about significant social benefits. Many studies have focused on adding antibacterial substances to the implant coating, and with a deeper understanding of the mechanism of implant failure, adding such substances by different modification methods has become a research hot spot. This review aims to summarize the antibacterial and anti-inflammatory substances that can be used as coating materials in orthopedic implants and to provide a reference for the prevention and treatment of implant failure caused by implant-related infection and excessive inflammation.

scholarly journals Sphingosine is able to prevent and eliminate Staphylococcus epidermidis biofilm formation on different orthopedic implant materials in vitro

2019 ◽  
Vol 98 (2) ◽  
pp. 209-219 ◽  
Author(s):  
Sascha Beck ◽  
Carolin Sehl ◽  
Sylvia Voortmann ◽  
Hedda Luise Verhasselt ◽  
Michael J. Edwards ◽  
...  
Keyword(s):  
Joint Replacement ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Orthopedic Implants ◽  
Antimicrobial Efficacy ◽  
Orthopedic Implant ◽  
Implant Materials ◽  
Joint Replacement Surgery ◽  
Replacement Surgery

Abstract Periprosthetic infection (PPI) is a devastating complication in joint replacement surgery. On the background of an aging population, the number of joint replacements and associated complications is expected to increase. The capability for biofilm formation and the increasing resistance of different microbes to antibiotics have complicated the treatment of PPI, requiring the need for the development of alternative treatment options. The bactericidal effect of the naturally occurring amino alcohol sphingosine has already been reported. In our study, we demonstrate the antimicrobial efficacy of sphingosine on three different strains of biofilm producing Staphylococcus epidermidis, representing one of the most frequent microbes involved in PPI. In an in vitro analysis, sphingosine’s capability for prevention and treatment of biofilm-contamination on different common orthopedic implant surfaces was tested. Coating titanium implant samples with sphingosine not only prevented implant contamination but also revealed a significant reduction of biofilm formation on the implant surfaces by 99.942%. When testing the antimicrobial efficacy of sphingosine on sessile biofilm-grown Staphylococcus epidermidis, sphingosine solution was capable to eliminate 99.999% of the bacteria on the different implant surfaces, i.e., titanium, steel, and polymethylmethacrylate. This study provides evidence on the antimicrobial efficacy of sphingosine for both planktonic and sessile biofilm-grown Staphylococcus epidermidis on contaminated orthopedic implants. Sphingosine may provide an effective and cheap treatment option for prevention and reduction of infections in joint replacement surgery. Key messages • Here we established a novel technology for prevention of implant colonization by sphingosine-coating of orthopedic implant materials. • Sphingosine-coating of orthopedic implants prevented bacterial colonization and significantly reduced biofilm formation on implant surfaces by 99.942%. • Moreover, sphingosine solution was capable to eliminate 99.999% of sessile biofilm-grown Staphylococcus epidermidis on different orthopedic implant surfaces.

scholarly journals Identification and Morphological Characterization of Biofilms Formed by Strains Causing Infection in Orthopedic Implants

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 649
Author(s):  
Débora C. Coraça-Huber ◽  
Lisa Kreidl ◽  
Stephan Steixner ◽  
Maximilian Hinz ◽  
Dietmar Dammerer ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Staphylococcus Epidermidis ◽  
Antibiotic Susceptibility ◽  
Biofilm Formation ◽  
Orthopedic Implants ◽  
Orthopedic Implant ◽  
Colony Forming Units ◽  
Scanning Electron

Objectives: For a better understanding of the mechanisms involved in biofilm formation, we performed a broad identification and characterization of the strains affecting implants by evaluating the morphology of biofilms formed in vitro in correlation with tests of the strains’ antibiotic susceptibility in planktonic form. The ability of the strains to form biofilms in vitro was evaluated by means of colony forming units counting, metabolic activity tests of biofilm cells, and scanning electron microscopy. Methods: A total of 140 strains were isolated from patients with orthopedic implant-related infections during the period of 2015 to 2018. The identification of the isolates was carried out through microbiological cultures and confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antibiotic susceptibility rates of the isolates were accessed according to EUCAST (European Committee on Antimicrobial Susceptibility Testing). The ability of all isolates to form biofilms in vitro was evaluated by counting the colony forming units, by measuring the metabolic activity of biofilm cells, and by analyzing the morphology of the formed biofilms using scanning electron microscopy. Results: From all the isolates, 41.84% (62 strains) were Staphylococcus epidermidis and 15.60% (22 strains) were Staphylococcus aureus. A significant difference in the capacity of biofilm formation was observed among the isolates. When correlating the biofilm forming capacity of the isolates to their antibiotic susceptibility rates, we observed that not all strains that were classified as resistant were biofilm producers in vitro. In other words, bacteria that are not good biofilm formers can show increased tolerance to multiple antibiotic substances. Conclusion: From 2015 until 2018, Staphylococcus epidermidis was the strain that caused most of the orthopedic implant-related infections in our hospital. Not all strains causing infection in orthopedic implants are able to form biofilms under in vitro conditions. Differences were observed in the number of cells and morphology of the biofilms. In addition, antibiotic resistance is not directly related to the capacity of the strains to form biofilms in vitro. Further studies should consider the use of in vitro culture conditions that better reproduce the joint environment and the growth of biofilms in humans.

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

The Predominant microRNAs in β-cell Clusters for Insulin Regulation and Diabetic Control

2020 ◽  
Vol 21 (7) ◽  
pp. 722-734
Author(s):  
Adele Soltani ◽  
Arefeh Jafarian ◽  
Abdolamir Allameh
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Diabetic Control ◽  
In Vitro Proliferation ◽  
Cell Functions ◽  
Mirna Expression Profiles ◽  
Multiple Processes ◽  
The Impact

micro (mi)-RNAs are vital regulators of multiple processes including insulin signaling pathways and glucose metabolism. Pancreatic β-cells function is dependent on some miRNAs and their target mRNA, which together form a complex regulative network. Several miRNAs are known to be directly involved in β-cells functions such as insulin expression and secretion. These small RNAs may also play significant roles in the fate of β-cells such as proliferation, differentiation, survival and apoptosis. Among the miRNAs, miR-7, miR-9, miR-375, miR-130 and miR-124 are of particular interest due to being highly expressed in these cells. Under diabetic conditions, although no specific miRNA profile has been noticed, the expression of some miRNAs and their target mRNAs are altered by posttranscriptional mechanisms, exerting diverse signs in the pathobiology of various diabetic complications. The aim of this review article is to discuss miRNAs involved in the process of stem cells differentiation into β-cells, resulting in enhanced β-cell functions with respect to diabetic disorders. This paper will also look into the impact of miRNA expression patterns on in vitro proliferation and differentiation of β-cells. The efficacy of the computational genomics and biochemical analysis to link the changes in miRNA expression profiles of stem cell-derived β-cells to therapeutically relevant outputs will be discussed as well.

scholarly journals Integrating Biosensors in Organs-on-Chip Devices: A Perspective on Current Strategies to Monitor Microphysiological Systems

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 110 ◽  
Author(s):  
Erika Ferrari ◽  
Cecilia Palma ◽  
Simone Vesentini ◽  
Paola Occhetta ◽  
Marco Rasponi
Keyword(s):  
Imaging Techniques ◽  
Biological Models ◽  
Electromechanical Properties ◽  
Human Organs ◽  
Tissue Constructs ◽  
Microphysiological Systems ◽  
Metabolic Activities ◽  
On Chip ◽  
Chip Analysis

Organs-on-chip (OoC), often referred to as microphysiological systems (MPS), are advanced in vitro tools able to replicate essential functions of human organs. Owing to their unprecedented ability to recapitulate key features of the native cellular environments, they represent promising tools for tissue engineering and drug screening applications. The achievement of proper functionalities within OoC is crucial; to this purpose, several parameters (e.g., chemical, physical) need to be assessed. Currently, most approaches rely on off-chip analysis and imaging techniques. However, the urgent demand for continuous, noninvasive, and real-time monitoring of tissue constructs requires the direct integration of biosensors. In this review, we focus on recent strategies to miniaturize and embed biosensing systems into organs-on-chip platforms. Biosensors for monitoring biological models with metabolic activities, models with tissue barrier functions, as well as models with electromechanical properties will be described and critically evaluated. In addition, multisensor integration within multiorgan platforms will be further reviewed and discussed.

scholarly journals DDRE-09. DEVELOPING IDO-PROTACS TO IMPROVE IMMUNOTHERAPEUTIC EFFICACY IN PATIENTS WITH GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii63-ii63
Author(s):  
Lakshmi Bollu ◽  
Derek Wainwright ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Time Course ◽  
Immune Cell ◽  
Enzyme Inhibitors ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Specific Protein ◽  
Cell Functions

Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

scholarly journals The Antibacterial Effects of Resin-Based Dental Sealants: A Systematic Review of In Vitro Studies

Materials ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 413
Author(s):  
Saad Saeed AlShahrani ◽  
Mana’a Saleh AlAbbas ◽  
Isadora Martini Garcia ◽  
Maha Ibrahim AlGhannam ◽  
Muath Abdulrahman AlRuwaili ◽  
...  
Keyword(s):  
Antibacterial Agents ◽  
Data Extraction ◽  
Risk Of Bias ◽  
Dental Sealants ◽  
Medium Risk ◽  
Metabolic Activities ◽  
High Degree ◽  
Phosphate Buffered Saline ◽  
Full Text Screening

This review aimed to assess the antimicrobial effects of different antibacterial agents/compounds incorporated in resin-based dental sealants. Four databases (PubMed, MEDLINE, Web of Science and Scopus) were searched. From the 8052 records retrieved, 275 records were considered eligible for full-text screening. Nineteen studies met the inclusion criteria. Data extraction and quality assessment was performed by two independent reviewers. Six of the nineteen included studies were judged to have low risk of bias, and the rest had medium risk of bias. Compounds and particles such as zinc, tin, Selenium, chitosan, chlorhexidine, fluoride and methyl methacrylate were found to be effective in reducing the colony-forming unit counts, producing inhibition zones, reducing the optical density, reducing the metabolic activities, reducing the lactic acid and polysaccharide production and neutralizing the pH when they are added to the resin-based dental sealants. In addition, some studies showed that the antibacterial effect was not significantly different after 2 weeks, 2 months and 6 months aging in distilled water or phosphate-buffered saline. In conclusion, studies have confirmed the effectiveness of adding antibacterial agents/compounds to dental sealants. However, we should consider that these results are based on laboratory studies with a high degree of heterogeneity.

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