Titanium (Ti) plays a predominant role as the material of choice in orthopaedic and dental implants. Despite the majority of Ti implants having long-term success, premature failure due to unsuccessful osseointegration leading to aseptic loosening is still too common. Recently, surface topography modification and biological/non-biological coatings have been integrated into orthopaedic/dental implants in order to mimic the surrounding biological environment as well as reduce the inflammation/infection that may occur. In this review, we summarize the impact of various Ti coatings on cell behaviour both in vivo and in vitro. First, we focus on the Ti surface properties and their effects on osteogenesis and then on bacterial adhesion and viability. We conclude from the current literature that surface modification of Ti implants can be generated that offer both osteoinductive and antimicrobial properties.
The use of biomaterials in orthopaedics for joint replacement, fracture healing and bone regeneration is a rapidly expanding field. Infection of these biomaterials is a major healthcare burden, leading to significant morbidity and mortality. Furthermore, the cost to healthcare systems is increasing dramatically. With advances in implant design and production, research has predominately focussed on osseointegration; however, modification of implant material, surface topography and chemistry can also provide antibacterial activity. With the increasing burden of infection, it is vitally important that we consider the bacterial interaction with the biomaterial and the host when designing and manufacturing future implants. During this review, we will elucidate the interaction between patient, biomaterial surface and bacteria. We aim to review current and developing surface modifications with a view towards antibacterial orthopaedic implants for clinical applications.
Sphingosine-1-phosphate (S1P) is a pleiotropic sphingolipid derived by the phosphorylation of sphingosine either by sphingosine kinase 1 (SPHK1) or SPHK2. Importantly, S1P acts through five different types of G-protein coupled S1P receptors (S1PRs) in immune cells to elicit inflammation and other immunological processes by enhancing the production of various cytokines, chemokines, and growth factors. The airway inflammation in asthma and other respiratory diseases is augmented by the activation of immune cells and the induction of T-helper cell type 2 (Th2)-associated cytokines and chemokines. Therefore, studying the S1P mediated signaling in airway inflammation is crucial to formulate effective treatment and management strategies for asthma and other respiratory diseases. The central aim of this study is to characterize the molecular targets induced through the S1P/S1PR axis and dissect the therapeutic importance of this key axis in asthma, airway inflammation, and other related respiratory diseases. To achieve this, we have adopted both high throughput next-generation knowledge discovery platforms such as SwissTargetPrediction, WebGestalt, Open Targets Platform, and Ingenuity Pathway Analysis (Qiagen, United States) to delineate the molecular targets of S1P and further validated the upstream regulators of S1P signaling using cutting edge multiple analyte profiling (xMAP) technology (Luminex Corporation, United States) to define the importance of S1P signaling in asthma and other respiratory diseases in humans.
Background: The progresses made in stem cell therapy offer an innovative approach and exhibit great potential for the repair of damaged organs and tissues. This study was conducted with a view to find the mechanisms responsible for the effectiveness of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the suppression of diabetes and experimentally-induced diabetic nephropathy.Methods: To realize this objective, diabetic and diabetic nephropathy subject groups that underwent MSC treatment were studied through numerous biochemistry and molecular genetics analyses.Results: The findings show that, relative to the control groups, the rats in the diabetic and diabetic nephropathy groups treated with stem cells infused with BM-MSCs showed a significant reversal in the levels of their insulin, glucose, heme-oxygenase-1 (HO-1) serum, and advanced glycation end product (AGEP). Moreover, BM-MSC therapy was also found to have a definite positive effect on the kidney functions. In addition, it also corresponded with a significant decrease in the availability of certain growth factors, namely the fibroblast growth factor (FGF), the platelet-derived growth factor (PDGF), and the transforming growth factor-β (TGF-β). BM-MSC treatment also improved the levels of expression of monocyte chemoatractant-1 (MCP-1) and interleukin-8 (IL-8) genes within kidney tissues. Lastly, the treatment recovered the organizational structure of the kidney and pancreas, a result demonstrated by a histopathological analysis. These results greatly coincide with those obtained through the biochemistry and molecular genetics analyses.Conclusion: Treatment using BM-MSCs is determined to be definitely effective in cases of diabetes and diabetic nephropathy.
Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection.
Tissue engineering provides new hope for the combination of cells, scaffolds, and bifactors for bone osteogenesis. This is achieved by mimicking the bone’s natural behavior in recruiting the cell’s molecular machinery for our use. Many researchers have focused on developing an ideal scaffold with specific features, such as good cellular adhesion, cell proliferation, differentiation, host integration, and load bearing. Various types of coating materials (organic and non-organic) have been used to enhance bone osteogenesis. In the last few years, RNA-mediated gene therapy has captured attention as a new tool for bone regeneration. In this review, we discuss the use of RNA molecules in coating and delivery, including messenger RNA (mRNA), RNA interference (RNAi), and long non-coding RNA (lncRNA) on different types of scaffolds (such as polymers, ceramics, and metals) in osteogenesis research. In addition, the effect of using gene-editing tools—particularly CRISPR systems—to guide RNA scaffolds in bone regeneration is also discussed. Given existing knowledge about various RNAs coating/expression may help to understand the process of bone formation on the scaffolds during osseointegration.
BACKGROUND: Mesenchymal stem cells (MSCs) and/or biological scaffolds have been used to regenerate articular cartilage with variable success. In the present study we evaluated cartilage regeneration using a combination of bone marrow (BM)-MSCs, Hyalofast TM and/or native cartilage tissue following full thickness surgical cartilage defect in rabbits. METHODS: Full-thickness surgical ablation of the medial-tibial cartilage was performed in New Zealand white (NZW) rabbits. Control rabbits (Group-I) received no treatment; Animals in other groups were treated as follows. Group-II: BM-MSCs (1 9 10 6 cells) ? Hyalofast TM ; Group-III: BMMSCs (1 9 10 6 cells) ? cartilage pellet (CP); and Group-IV: BM-MSCs (1 9 10 6 cells) ? Hyalofast TM ? CP. Animals were sacrificed at 12 weeks and cartilage regeneration analyzed using histopathology, International Cartilage Repair Society (ICRS-II) score, magnetic resonance observation of cartilage repair tissue (MOCART) score and biomechanical studies. RESULTS: Gross images showed good tissue repair (Groups IV [ III [ Group II) and histology demonstrated intact superficial layer, normal chondrocyte arrangement, tidemark and cartilage matrix staining (Groups III and IV) compared to the untreated control (Group I) respectively. ICRS-II score was 52.5, 65.0, 66 and 75% (Groups I-IV) and the MOCART score was 50.0, 73.75 and 76.25 (Groups II-IV) respectively. Biomechanical properties of the regenerated cartilage tissue in Group IV closed resembled that of a normal cartilage. CONCLUSION: Hyalofast TM together with BM-MSCs and CP led to efficient cartilage regeneration following full thickness surgical ablation of tibial articular cartilage in vivo in rabbits. Presence of hyaluronic acid in the scaffold and native microenvironment cues probably facilitated differentiation and integration of BM-MSCs.
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