FRESH GAS UTILIZATION OF EIGHT CIRCLE SYSTEMS

The fresh gas utilization (FGU) of a semi-closed breathing system is defined as the ratio of the amount of gas reaching the patient's lungs to the total amount of fresh gas flowing into the breathing system. It indicates to what extent a breathing system conserves anaesthetic gases and provides inspired gas concentrations as close as possible to those in the fresh gas, even at low fresh gas flows (FGF). We have measured FGU in eight circle systems used conventionally in Europe: Drager Cicero, Drager Sulla 808V with circle system 8 ISO and ventilator Ventilog, Drager AV1, Ohmeda Modulus II Plus, Gambro Engstrdm Elsa, Siemens Servo Ventilator 900 D with circle system 985, Siemens Ventilator 710 and Megamed 700A with circle system 219. The Tests were performed according to the Draft European Standard ‘Anaesthetic Workstations and Their Modules'. None of the systems tested showed the characteristics of an ideal system which would reach 100% FGU with an FGF less than minute volume. At FGF 3 litre min−1, FGU was: Gambro Engstrdm Elsa 97.8% Siemens Servo Ventilator 900 D with circle system 96.1 %, Drager Cicero 93.4%, Ohmeda Modulus II Plus 93.1 %, Drager 8 ISO 92.3%, Drager AVI 87.6%, Megamed 700A 77.0% and Siemens Ventilator 710 74.1

Animal models for bone tissue engineering and modelling disease

Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches

Modeling the growth of multicellular cancer spheroids in a\ud bioengineered 3D microenvironment and their treatment with an\ud anti-cancer drug

A critical step in the dissemination of ovarian cancer cells is the formation of multicellular spheroids from cells shed from the primary tumor. The objectives of this study were to establish and validate bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer cells in vitro and simultaneously to develop computational models describing the growth of multicellular spheroids in these bioengineered matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and cultured for up to 4 weeks. Immunohistochemistry was used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel.\ud \ud Two computational models were developed. In the first model, each spheroid was treated as an incompressible porous medium, whereas in the second model the concept of morphoelasticity was used to incorporate details about internal stresses and strains. Each model was formulated as a free boundary problem. Functional forms for cell proliferation and apoptosis motivated by the experimental work were applied and the predictions of both models compared with the output from the experiments. Both models simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture time and treatment with paclitaxel. Our mathematical models provide new perspectives on previous experimental results and have informed the design of new 3D studies of multicellular cancer spheroids

Growth of confined cancer spheroids: a combined experimental and mathematical modelling approach

We have integrated a bioengineered three-dimensional platform by generating multicellular cancer spheroids in a controlled microenvironment with a mathematical model to investigate\ud confined tumour growth and to model its impact on cellular processes

Parents d'enfants hospitalisés dans une unité de soins intensifs: une étude exploratoire de leur vécu.

Le travail présenté ici repose sur une recherche qualitative effectuée par l'Institut universitaire de médecine sociale et préventive de Lausanne (IUMSP), sur l'initiative de l'unité des soins intensifs médico-chirurgicaux de pédiatrie (SIP) du Centre hospitalier universitaire vaudois (CHUV). Cette étude détaille le vécu de parents dont l'enfant a été hospitalisé dans une unité de soins intensifs. Il a paru essentiel aux initiateurs du projet d'imaginer offrir un accompagnement et une aide de type préventif aux personnes concernées par la maladie ou l'accident de leur enfant. Toutefois, avant de procéder à ce dispositif, il convenait de savoir plus précisément: 1. Ce que les parents vivaient durant l'hospitalisation de leur enfant; 2. Quels étaient leurs besoins et leurs attentes (à l'égard de l'unité, à l'égard des soignants) en pareilles circonstances

In vitro pre-vascularisation of tissue-engineered constructs A co-culture perspective

In vitro pre-vascularization is one of the main vascularization strategies in the tissue engineering field. Culturing cells within a tissue-engineered construct (TEC) prior to implantation provides researchers with a greater degree of control over the fate of the cells. However, balancing the diverse range of different cell culture parameters in vitro is seldom easy and in most cases, especially in highly vascularized tissues, more than one cell type will reside within the cell culture system. Culturing multiple cell types in the same construct presents its own unique challenges and pitfalls. The following review examines endothelial-driven vascularization and evaluates the direct and indirect role other cell types have in vessel and capillary formation. The article then analyses the different parameters researchers can modulate in a co-culture system in order to design optimal tissue-engineered constructs to match desired clinical applications

Melimine-Modified 3D-Printed Polycaprolactone Scaffolds for the Prevention of Biofilm-Related Biomaterial Infections

Biomaterial-associated infections are one of the major causes of implant failure. These infections result from persistent bacteria that have adhered to the biomaterial surface before, during, or after surgery and have formed a biofilm on the implant's surface. It is estimated that 4 to 10% of implant surfaces are contaminated with bacteria; however, the infection rate can be as high as 30% in intensive care units in developed countries and as high as 45% in developing countries. To date, there is no clinical solution to prevent implant infection without relying on the use of high doses of antibiotics supplied systemically and/or removal of the infected device. In this study, melimine, a chimeric cationic peptide that has been tested in Phase I and II human clinical trials, was immobilized onto the surface of 3D-printed medical-grade polycaprolactone (mPCL) scaffolds via covalent binding and adsorption. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) spectra of melimine-treated surfaces confirmed immobilization of the peptide, as well as its homogeneous distribution throughout the scaffold surface. Amino acid analysis showed that melimine covalent and noncovalent immobilization resulted in a peptide density of ∼156 and ∼533 ng/cm2, respectively. Furthermore, we demonstrated that the immobilization of melimine on mPCL scaffolds by 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (EDC) coupling and noncovalent interactions resulted in a reduction of Staphylococcus aureus colonization by 78.7% and 76.0%, respectively, in comparison with the nonmodified control specimens. Particularly, the modified surfaces maintained their antibacterial properties for 3 days, which resulted in the inhibition of biofilm formation in vitro. This system offers a biomaterial strategy to effectively prevent biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment

Cavin-1/PTRF alters prostate cancer cell-derived extracellular vesicle content and internalization to attenuate extracellular vesicle-mediated osteoclastogenesis and osteoblast proliferation

Background: Tumour-derived extracellular vesicles (EVs) play a role in tumour progression; however, the spectrum of molecular mechanisms regulating EV secretion and cargo selection remain to be fully elucidated. We have reported that cavin-1 expression in prostate cancer PC3 cells reduced the abundance of a subset of EV proteins, concomitant with reduced xenograft tumour growth and metastasis. Methods: We examined the functional outcomes and mechanisms of cavin-1 expression on PC3-derived EVs (PC3-EVs). Results: PC3-EVs were internalized by osteoclast precursor RAW264.7 cells and primary human osteoblasts (hOBs) in vitro, stimulating osteoclastogenesis 37-fold and hOB proliferation 1.5-fold, respectively. Strikingly, EVs derived from cavin-1-expressing PC3 cells (cavin-1-PC3-EVs) failed to induce multinucleate osteoblasts or hOB proliferation. Cavin-1 was not detected in EVs, indicating an indirect mechanism of action. EV morphology, size and quantity were also not affected by cavin-1 expression, suggesting that cavin-1 modulated EV cargo recruitment rather than release. While cavin-1-EVs had no osteoclastogenic function, they were internalized by RAW264.7 cells but at a reduced efficiency compared to control EVs. EV surface proteins are required for internalization of PC3-EVs by RAW264.7 cells, as proteinase K treatment abolished uptake of both control and cavin-1-PC3-EVs. Removal of sialic acid modifications by neuraminidase treatment increased the amount of control PC3-EVs internalized by RAW264.7 cells, without affecting cavin-1-PC3-EVs. This suggests that cavin-1 expression altered the glycosylation modifications on PC3-EV surface. Finally, cavin-1 expression did not affect EV in vivo tissue targeting as both control and cavin-1-PC3-EVs were predominantly retained in the lung and bone 24 hours after injection into mice. Discussion: Taken together, our results reveal a novel pathway for EV cargo sorting, and highlight the potential of utilizing cavin-1-mediated pathways to attenuate metastatic prostate cancer

Assessment of static and perfusion methods for decellularization of PCL membrane-supported periodontal ligament cell sheet constructs

Decellularization aims to harness the regenerative properties of native extracellular matrix. The objective of this study was to evaluate different methods of decellularization of periodontal ligament cell sheets whilst maintaining their structural and biological integrity.Human periodontal ligament cell sheets were placed onto melt electrospun polycaprolactone (PCL) membranes that reinforced the cell sheets during the various decellularization protocols. These cell sheet constructs (CSCs) were decellularized under static/perfusion conditions using a) 20 mM ammonium hydroxide (NH4OH)/Triton X-100, 0.5% v/v; and b) sodium dodecyl sulfate (SDS, 0.2% v/v), both +/- DNase besides Freeze-thaw (F/T) cycling method. CSCs were assessed using a collagen quantification assay, immunostaining and scanning electron microscopy. Residual fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were assessed with Bio-plex assays.DNA removal without DNase was higher under static conditions. However, after DNase treatment, there were no differences between the different decellularization methods with virtually 100% DNA removal. DNA elimination in F/T was less efficient even after DNase treatment. Collagen content was preserved with all techniques, except with SDS treatment. Structural integrity was preserved after NH4OH/Triton X-100 and F/T treatment, while SDS altered the extracellular matrix structure. Growth factor amounts were reduced after decellularization with all methods, with the greatest reduction (to virtually undetectable amounts) following SDS treatment, while NH4OH/Triton X-100 and DNase treatment resulted in approximately 10% retention.This study showed that treatment with NH4OH/Triton X-100 and DNase solution was the most efficient method for DNA removal and the preservation of extracellular matrix integrity and growth factors retention