The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective

Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH) and the Medical Research Council (MRC) have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the "European Advanced Translational Research InfraStructure in Medicine" (EATRIS). It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society

Ischaemic Preconditioning Protects Against Ischaemia/Reperfusion Injury: Emerging Concepts

AbstractIntroductionIschaemic preconditioning (IP) has emerged as a powerful method of ameliorating ischaemia/reperfusion (I/R) injury to the myocardium. This review investigates whether this phenomenon is universally applicable in modulating I/R injury to other tissues.MethodsA Medline search was conducted to identify both animal and human studies that described IP-induced protection from I/R injury in a variety of non-cardiac organ systems. Particular emphasis was placed on elucidation of underlying physiological concepts.Results and conclusionsIP utilises endogenous mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. To date there are few human studies, but recent reports suggest that human liver, lung and skeletal muscle acquire similar protection after IP. Specifically, preconditioned tissues exhibit reduced energy requirements, altered energy metabolism, better electrolyte homeostasis and genetic re-organisation, giving rise to the concept of ‘ischaemia tolerance’. IP also induces ‘reperfusion tolerance’ with less reactive oxygen species and activated neutrophils released, reduced apoptosis and better microcirculatory perfusion compared to non-preconditioned tissue. Systemic I/R injury is also diminished by preconditioning. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena

A Global Challenge: Sustainability of Submicrometer PEO and PVP Fiber Production

The field of submicrometer polymeric production currently has a predominant research focus on morphology and application. In comparison, the sustainability of the manufacture of submicrometer polymeric fibers, specifically the energy efficiency, is less explored. The principles of Green Chemistry and Green Engineering outline frameworks for the manufacture of “greener” products, where the most significant principles in the two frameworks are shown to be centered on energy efficiency, material wastage, and the use of non-hazardous materials. This study examines the power consumption during the production of Polyethylene oxide (PEO) and Polyvinylpyrrolidone (PVP) submicrometer fibers under magnitudes of the key forming parameters to generate fibers via pressure spinning. The energy consumption, along with the fiber diameter, and production rate during the manufacture of fibers is predominantly attributed to the characteristics of polymeric solutions utilized

Optical properties of tissue measured using terahertz pulsed imaging.

The first demonstrations of terahertz imaging in biomedicine were made several years ago, but few data are available on the optical properties of human tissue at terahertz frequencies. A catalogue of these properties has been established to estimate variability and determine the practicality of proposed medical applications in terms of penetration depth, image contrast and reflection at boundaries. A pulsed terahertz imaging system with a useful bandwidth 0.5-2.5 THz was used. Local ethical committee approval was obtained. Transmission measurements were made through tissue slices of thickness 0.08 to 1 mm, including tooth enamel and dentine, cortical bone, skin, adipose tissue and striated muscle. The mean and standard deviation for refractive index and linear attenuation coefficient, both broadband and as a function of frequency, were calculated. The measurements were used in simple models of the transmission, reflection and propagation of terahertz radiation in potential medical applications. Refractive indices ranged from 1.5 ± 0.5 for adipose tissue to 3.06 ± 0.09 for tooth enamel. Significant differences (P<0.05) were found between the broadband refractive indices of a number of tissues. Terahertz radiation is strongly absorbed in tissue so reflection imaging, which has lower penetration requirements than transmission, shows promise for dental or dermatological applications

Latest developments in innovative manufacturing to combine nanotechnology with healthcare

Nanotechnology has become increasingly important in advancing the frontiers of many key areas of healthcare, for example, drug delivery and tissue engineering. To fully harness the many benefits of nanotechnology in healthcare, innovative manufacturing is necessary to mass produce nanoparticles and nanofibers, the two major types of nanofeatures currently sought after and of immense utilitarian value in healthcare. For example, nanoparticles are a key drug delivery enabler, the structural and mechanical mimicry are important attributes of nanofiber which are increasingly used as biomimetic agents

Flexible and Wearable Graphene-based Terahertz Antenna for Body-Centric Applications

This paper presents a graphene-based wearable antenna operating in the terahertz frequency range. Graphene with its highly attractive electronic properties, and modern manufacturing techniques can yield antennas that are not only flexible but efficient and low-profile, suited for terahertz applications. The graphene antenna investigated here has a resonant frequency of 0.647 THz. The performance of the antenna is evaluated on-body and in free space using three layers of human skin. Simulated results show that the proposed antenna has a bandwidth of 20 GHz and offers a radiation efficiency of 96% in free space and 50% on the body, with respective gains of 7.8 dB and 7 dB. The small and flexible structure of the antenna along with excellent impedance matching, high bandwidth, and gain, and good efficiency makes it an appropriate candidate to shortrange wireless communication in the vicinity of the human body

Current methodologies and approaches for the formation of core–sheath polymer fibers for biomedical applications

The application of polymer fibers has rocketed to unimaginable heights in recent years and occupies every corner of our day-to-day life, from knitted protective textile clothes to buzzing smartphone electronics. Polymer fibers could be obtained from natural and synthetic polymers at a length scale from the nanometer to micrometer range. These fibers could be formed into different configurations such as single, core–sheath, hollow, blended, or composite according to human needs. Of these several conformations of fibers, core–sheath polymer fibers are an interesting class of materials, which shows superior physical, chemical, and biological properties. In core–sheath fiber structures, one of the components called a core is fully surrounded by the second component known as a sheath. In this format, different polymers can be applied as a sheath over a solid core of another polymer, thus resulting in a variety of modified properties while maintaining the major fiber property. After a brief introduction to core–sheath fibers, this review paper focuses on the development of the electrospinning process to manufacture core–sheath fibers followed by illustrating the current methodology and approaches to form them on a larger scale, suitable for industrial manufacturing and exploitation. Finally, the paper reviews the applications of the core–sheath fibers, in particular, recent studies of core–sheath polymer fibers in tissue engineering (nerve, vascular grafts, cardiomyocytes, bone, tendons, sutures, and wound healing), growth factors and other bioactive component release, and drug delivery. Therefore, core–sheath structures are a revolutionary development in the field of science and technology, becoming a backbone to many emerging technologies and novel opportunities

An in silico study of the influence of vessel wall deformation on neointimal hyperplasia progression in peripheral bypass grafts

Neointimal hyperplasia (NIH) is a major obstacle to graft patency in the peripheral arteries. A complex interaction of biomechanical factors contribute to NIH development and progression, and although haemodynamic markers such as wall shear stress have been linked to the disease, these have so far been insufficient to fully capture its behaviour. Using a computational model linking computational fluid dynamics (CFD) simulations of blood flow with a biochemical model representing NIH growth mechanisms, we analyse the effect of compliance mismatch, due to the presence of surgical stitches and/or to the change in distensibility between artery and vein graft, on the haemodynamics in the lumen and, subsequently, on NIH progression. The model enabled to simulate NIH at proximal and distal anastomoses of three patient-specific end-to-side saphenous vein grafts under two compliance-mismatch configurations, and a rigid wall case for comparison, obtaining values of stenosis similar to those observed in the computed tomography (CT) scans. The maximum difference in time-averaged wall shear stress between the rigid and compliant models was 3.4 Pa, and differences in estimation of NIH progression were only observed in one patient. The impact of compliance on the haemodynamic-driven development of NIH was small in the patient-specific cases considered

The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease

Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries

Novel pressurised gyration device for making core-sheath polymer fibres

Core-sheath fibres of two polymers were generated using a novel set-up where rotating speed and pressure can be varied at ambient temperature. The specially designed spinneret consists of inner and outer chambers which can accommodate two polymers and other additives. The new methodology was demonstrated using poly(ethylene oxide) and poly(methylmethacrylate) (PMMA). Dyes were used as colouring agents for the polymers to verify core-sheath formation, and optical, scanning and fluorescent microscopy of the formed fibres confirmed the presence of a core-sheath combination. The core diameter obtained was in the range 5–10 μm and the sheath fibre diameter was 20–30 μm. The core/sheath diameter can be pre-set by selecting the forming conditions. To show the flexibility of the new method, nanoparticle containing PMMA fibres were also produced using the new device and incorporation of the nanoparticles in the sheath and core of the fibres was verified by electron microscopy and energy-dispersive X-ray spectroscopy analysis. A high yield of fibre was obtained and with more severe forming conditions the size of core-sheath fibres generated can be reduced to the nanoscale. Thus, the new process has a real capability of manufacturing a wide variety of novel functional materials and structures in a single scalable set-up