Silsesquioxane polymer as a potential scaffold for laryngeal reconstruction

Cancer, disease and trauma to the larynx and their treatment can lead to permanent loss of structures critical to voice, breathing and swallowing. Engineered partial or total laryngeal replacements would need to match the ambitious specifications of replicating functionality, outer biocompatibility, and permissiveness for an inner mucosal lining. Here we present porous polyhedral oligomeric silsesquioxane-poly(carbonate urea) urethane (POSS-PCUU) as a potential scaffold for engineering laryngeal tissue. Specifically, we employ a precipitation and porogen leaching technique for manufacturing the polymer. The polymer is chemically consistent across all sample types and produces a foam-like scaffold with two distinct topographies and an internal structure composed of nano- and micro-pores. Whilst the highly porous internal structure of the scaffold contributes to the complex tensile behaviour of the polymer, the surface of the scaffold remains largely non-porous. The low number of pores minimise access for cells, although primary fibroblasts and epithelial cells do attach and proliferate on the polymer surface. Our data show that with a change in manufacturing protocol to produce porous polymer surfaces, POSS-PCUU may be a potential candidate for overcoming some of the limitations associated with laryngeal reconstruction and regeneration

The Host Immune Response to Tissue-Engineered Organs: Current Problems and Future Directions

As the global health burden of chronic disease increases, end-stage organ failure has become a costly and intractable problem. De novo organ creation is one of the long-term goals of the medical community. One of the promising avenues is that of tissue engineering: the use of biomaterials to create cells, structures, or even whole organs. Tissue engineering has emerged from its nascent stage, with several proof-of-principle trials performed across various tissue types. As tissue engineering moves from the realm of case trials to broader clinical study, three major questions have emerged: (1) Can the production of biological scaffolds be scaled up accordingly to meet current and future demands without generating an unfavorable immune response? (2) Are biological scaffolds plus or minus the inclusion of cells replaced by scar tissue or native functional tissue? (3) Can tissue-engineered organs be grown in children and adolescents given the different immune profiles of children? In this review, we highlight current research in the immunological response to tissue-engineered biomaterials, cells, and whole organs and address the answers to these questions

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species. Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database. Three over-the-counter non-steroidal anti-inflammatory drugs were also included in the screening. The 2-arylpropanoic acids, including IBP, were comprehensively evaluated against phenotypically and physiologically different strains of mycobacteria, and their cytotoxicity was determined against murine RAW264.7 macrophages. Furthermore, a comparative bioinformatic analysis was employed to propose a potential mycobacterial target. Results: IBP showed antitubercular properties while carprofen was the most potent among the 2-arylpropanoic class. A 3,5-dinitro-IBP derivative was found to be more potent than IBP but equally selective. Other synthetic derivatives of IBP were less active, and the free carboxylic acid of IBP seems to be essential for its anti-TB activity. IBP, carprofen and the 3,5-dinitro-IBP derivative exhibited activity against multidrug-resistant isolates and stationary phase bacilli. On the basis of the human targets of the 2-arylpropanoic analgesics, the protein initiation factor infB (Rv2839c) of M tuberculosis was proposed as a potential molecular target. Conclusions: The HT-SPOTi method can be employed reliably and reproducibly to screen the antimicrobial potency of different compounds. IBP demonstrated specific antitubercular activity, while carprofen was the most selective agent among the 2-arylpropanoic class. Activity against stationary phase bacilli and multidrug-resistant isolates permits us to speculate a novel mechanism of antimycobacterial action. Further medicinal chemistry and target elucidation studies could potentially lead to new therapies against TB

Demonstrating an absolute quantum advantage in direct absorption measurement

Engineering apparatus that harness quantum theory promises to offer practical advantages over current technology. A fundamentally more powerful prospect is that such quantum technologies could out-perform any future iteration of their classical counterparts, no matter how well the attributes of those classical strategies can be improved. Here, for optical direct absorption measurement, we experimentally demonstrate such an instance of an absolute advantage per photon probe that is exposed to the absorbative sample. We use correlated intensity measurements of spontaneous parametric downconversion using a commercially available air-cooled CCD, a new estimator for data analysis and a high heralding efficiency photon-pair source. We show this enables improvement in the precision of measurement, per photon probe, beyond what is achievable with an ideal coherent state (a perfect laser) detected with 100% efficient and noiseless detection. We see this absolute improvement for up to 50% absorption, with a maximum observed factor of improvement of 1.46. This equates to around 32% reduction in the total number of photons traversing an optical sample, compared to any future direct optical absorption measurement using classical light

Respiratory simulator for robotic respiratory tract treatments

Robotic healthcare is a growing and multi-faceted field where robots help perform surgery, remotely provide care to patients, aid in supplying various physical therapies and further medical research. Robotic simulators of human physiology provide a powerful platform to advance the development of novel treatments, prostheses and therapies. This study focuses on the design, building, testing and characterisation of a novel simulator of the human respiratory system. The comparison between healthy subjects breathing and coughing physiological values and the values achieved utilising our novel bioinspired respiratory simulator shows that the latter is able to reproduce peak flow rates and volumes

Prediction of larynx function using multichannel surface EMG classification

Total laryngectomy (TL) affects critical functions such as swallowing, coughing and speaking. An artificial, bioengineered larynx (ABL), operated via myoelectric signals, may improve quality of life for TL patients. To evaluate the efficacy of using surface electromyography (sEMG) as a control signal to predict instances of swallowing, coughing and speaking, sEMG was recorded from submental, intercostal and diaphragm muscles. The cohort included TL and control participants. Swallowing, coughing, speaking and movement actions were recorded, and a range of classifiers were investigated for prediction of these actions. Our algorithm achieved F1-scores of 76.0 ± 4.4 % (swallows), 93.8 ± 2.8 % (coughs) and 70.5 ± 5.4 % (speech) for controls, and 67.7 ± 4.4 % (swallows), 71.0 ± 9.1 % (coughs) and 78.0 ± 3.8 % (speech) for TLs, using a random forest (RF) classifier. 75.1 ± 6.9 % of swallows were detected within 500 ms of onset in the controls, and 63.1 ± 6.1 % in TLs. sEMG can be used to predict critical larynx movements, although a viable ABL requires improvements. Results are particularly encouraging as they encompass a TL cohort. An ABL could alleviate many challenges faced by laryngectomees. This study represents a promising step toward realising such a device

Improving cellular migration in tissue-engineered laryngeal scaffolds

ObjectiveTo modify the non-porous surface membrane of a tissue-engineered laryngeal scaffold to allow effective cell entry.MethodsThe mechanical properties, surface topography and chemistry of polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane were characterised. A laser technique introduced surface perforations. Micro computed tomography generated porosity data. Scaffolds were seeded with cells, investigated histologically and proliferation studied. Incubation and time effects were assessed.ResultsLaser cutting perforated the polymer, connecting the substructure with the ex-scaffold environment and increasing porosity (porous, non-perforated = 87.9 per cent; porous, laser-perforated at intensities 3 = 96.4 per cent and 6 = 89.5 per cent). Cellular studies confirmed improved cell viability. Histology showed cells adherent to the scaffold surface and cells within perforations, and indicated that cells migrated into the scaffolds. After 15 days of incubation, scanning electron microscopy revealed an 11 per cent reduction in pore diameter, correlating with a decrease in Young's modulus.ConclusionIntroducing surface perforations presents a viable method of improving polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane as a tissue-engineered scaffold

A Bioinspired Active Robotic Simulator of the Human Respiratory System

Pathologies affecting the respiratory system can lead to a debilitating decrease in quality of life and can be fatal. To test medical devices and implants for the human respiratory system, a simulation system that can reproduce multiple respiratory features is necessary. Currently available respiratory simulators only focus on reproducing flow rate profiles of breathing while coughing simulators focus on aerosol analysis. In this paper we propose a novel, bioinspired robotic simulator that can physically replicate both breathing and coughing flow rate characteristics of healthy adults. We conducted a study on 31 healthy adult participants to gather the flow rate measurement of normal breathing, deep breathing, breathing while running and coughing. Coughing flow rate profiles vary considerably between participants, making an accurate simulation of coughs a challenge. To enable cough flow rate simulation, a new methodology based on the identification of four cough phases, Attack, Decay, Sustain and Release (ADSR) and their parametrization was devised. This methodology leads to the unprecedented ability to reproduce diverse and complex coughing flow rate profiles. Our simulator is able to reproduce respiratory flows with a root mean square error (RMSE) of 1.8 L/min between normal participant breathing and its simulation, 5% of the maximum flow rate simulated for that participant (pMFR), an RMSE of 10.08 L/min for deep breathing, 18% of the pMFR and an RMSE of 13.29 L/min for exertion breathing, 17% of pMFR. For the simulation of an average cough we recorded an RMSE of 51.43 L/min, 13% of the pMFR and for a low flow rate cough an RMSE of 12.38 L/min, 9.5% of the pMFR. The presented simulator matches the fundamentals of human breathing and coughing, advancing the current capability of respiratory system simulators