Shervanthi Homer-Vanniasinkam

Delivery of mesenchymal stem cells in biomimetic engineered scaffolds promotes healing of diabetic ulcers.

AIMnWe hypothesized that delivery of mesenchymal stem cells (MSCs) in a biomimetic collagen scaffold improves wound healing in a diabetic mouse model.nnnMATERIALS & METHODSnRolled collagen scaffolds containing MSCs were implanted or applied topically to diabetic C57BL/6 mice with excisional wounds.nnnRESULTSnRolled scaffolds were hypoxic, inducing MSC synthesis and secretion of VEGF. Diabetic mice with wounds treated with rolled scaffolds containing MSCs showed increased healing compared with controls. Histologic examination showed increased cellular proliferation, increased VEGF expression and capillary density, and increased numbers of macrophages, fibroblasts and smooth muscle cells. Addition of laminin to the collagen scaffold enhanced these effects.nnnCONCLUSIONnActivated MSCs delivered in a biomimetic-collagen scaffold enhanced wound healing in a translationally relevant diabetic mouse model.

Polymer–Magnetic Composite Fibers for Remote-Controlled Drug Release

An efficient method is reported, for the fabrication of composite microfibers that can be magnetically actuated and are biocompatible, targeting controlled drug release. Aqueous solutions of polyvinyl alcohol, incorporated with citric acid-coated Fe3O4 magnetic nanoparticles (MNPs), are subject to infusion gyration to generate 100-300 nm diameter composite fibers, with controllable MNP loading. The fibers are stable in polar solvents, such as ethanol, and do not show any leaching of MNPs for over 4 weeks. Using acetaminophen as an example, we demonstrate that this material is effective in immobilization and triggered release of drugs, which is achieved by a moving external magnetic field. The remote actuation ability, coupled with biocompatibility and lightweight property, renders enormous potential for these fibers to be used as a smart drug release agent.

Patient-Specific, Multi-Scale Modeling of Neointimal Hyperplasia in Vein Grafts

Neointimal hyperplasia is amongst the major causes of failure of bypass grafts. The disease progression varies from patient to patient due to a range of different factors. In this paper, a mathematical model will be used to understand neointimal hyperplasia in individual patients, combining information from biological experiments and patient-specific data to analyze some aspects of the disease, particularly with regard to mechanical stimuli due to shear stresses on the vessel wall. By combining a biochemical model of cell growth and a patient-specific computational fluid dynamics analysis of blood flow in the lumen, remodeling of the blood vessel is studied by means of a novel computational framework. The framework was used to analyze two vein graft bypasses from one patient: a femoro-popliteal and a femoro-distal bypass. The remodeling of the vessel wall and analysis of the flow for each case was then compared to clinical data and discussed as a potential tool for a better understanding of the disease. Simulation results from this first computational approach showed an overall agreement on the locations of hyperplasia in these patients and demonstrated the potential of using new integrative modeling tools to understand disease progression.

Computational tools for clinical support : a multi-scale compliant model for haemodynamic simulations in an aortic dissection based on multi-modal imaging data

Aortic dissection (AD) is a vascular condition with high morbidity and mortality rates. Computational fluid dynamics (CFD) can provide insight into the progression of AD and aid clinical decisions; however, oversimplified modelling assumptions and high computational cost compromise the accuracy of the information and impede clinical translation. To overcome these limitations, a patient-specific CFD multi-scale approach coupled to Windkessel boundary conditions and accounting for wall compliance was developed and used to study a patient with AD. A new moving boundary algorithm was implemented to capture wall displacement and a rich in vivo clinical dataset was used to tune model parameters and for validation. Comparisons between in silico and in vivo data showed that this approach successfully captures flow and pressure waves for the patient-specific AD and is able to predict the pressure in the false lumen (FL), a critical variable for the clinical management of the condition. Results showed regions of low and oscillatory wall shear stress which, together with higher diastolic pressures predicted in the FL, may indicate risk of expansion. This study, at the interface of engineering and medicine, demonstrates a relatively simple and computationally efficient approach to account for arterial deformation and wave propagation phenomena in a three-dimensional model of AD, representing a step forward in the use of CFD as a potential tool for AD management and clinical support.

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.

High-resolution 3D printing for healthcare underpinned by small-scale fluidics

In this chapter we concentrate on recent developments in small-scale fluidics assisted high-resolution (<10xa0μm) 3D printing technologies and their potential transformative impact and applications in healthcare. We start by outlining the clinical context and healthcare needs driving some of the most exciting developments in the high-resolution printing and healthcare manufacture, which are poised to underpin the growth of major new health and care paradigms such as personalized medicine and medical devices; minimally invasive surgical interventions and sensors; biorobotics, bionics and human-machine interfaces enabled by haptics technologies; sensing and stimulation devices; and theranostic and bioresorbable medical devices. This is followed by a brief review of a few techniques for 3D printing at high-resolution, including direct-write and electrohydrodynamic printing where small (micro and nano) scale fluidics plays a vital role in improving reliability and achieving resolutions at the limit of current photolithographic techniques. Next we discuss the fundamentals of small-scale flows and materials considerations in designing “inks” for 3D printing. This includes expounding on the role of two key parameters, ink rheology and surface energy, in deciding the printing resolution. Then we discuss some healthcare related exemplar structures that have exploited high-resolution 3D printing and, in particular, emphasize the unique features of high-resolution printing that suit these applications. These include discussion on electronic interconnects and healthcare sensors, bio-scaffolds and their functional properties, cell signaling and the role of site-specific materials deposition for biology-on-a-chip type applications. Lastly, we will provide a perspective on future developments in the technology and its potential impact on shaping the future of healthcare applications such as miniature wearable and implantable sensing, (personalised) implantable devices, soft robotics and haptics, etc.

A simplified method to account for wall motion in patient-specific blood flow simulations of aortic dissection : comparison with fluid-structure interaction

Aortic dissection (AD) is a complex and highly patient-specific vascular condition difficult to treat. Computational fluid dynamics (CFD) can aid the medical management of this pathology, yet its modelling and simulation are challenging. One aspect usually disregarded when modelling AD is the motion of the vessel wall, which has been shown to significantly impact simulation results. Fluid-structure interaction (FSI) methods are difficult to implement and are subject to assumptions regarding the mechanical properties of the vessel wall, which cannot be retrieved non-invasively. This paper presents a simplified moving-boundary method (MBM) to account for the motion of the vessel wall in type-B AD CFD simulations, which can be tuned with non-invasive clinical images (e.g. 2D cine-MRI). The method is firstly validated against the 1D solution of flow through an elastic straight tube; it is then applied to a type-B AD case study and the results are compared to a state-of-the-art, full FSI simulation. Results show that the proposed method can capture the main effects due to the wall motion on the flow field: the average relative difference between flow and pressure waves obtained with the FSI and MBM simulations was less than 1.8% and 1.3%, respectively and the wall shear stress indices were found to have a similar distribution. Moreover, compared to FSI, MBM has the advantage to be less computationally expensive (requiring half of the time of an FSI simulation) and easier to implement, which are important requirements for clinical translation.

Paper-based Potentiometric Sensing of Free Bilirubin in Blood Serum

Bilirubin is predominantly formed in the liver as a result of breakdown of hemoglobin. Knowing the concentration of bilirubin in serum is important in evaluating the health of the liver, and for the diagnosis of hyperbilirubinemia (a condition that afflicts approximately 60% of full-term and 80% of pre-term newborns). This paper describes the design and fabrication of a potentiometric sensor for the determination of free bilirubin in serum. The sensor has a polymeric ion-selective membrane, and selectively measures free ionic bilirubin (unbound bilirubin - i.e., bilirubin not complexed to albumin or other complexing agents), in the presence of other anions - chloride, phosphate, pyruvate, deoxycholate, and lactate - also present in serum. The linear response range of the sensor (1.0u202fmM to 0.10u202fμM bilirubin, measured in a sodium phosphate buffer with pH 8.6) covers the clinically-relevant concentration of bilirubin in serum (5-500u202fμM). Free bilirubin could be detected in human blood serum with this potentiometric sensor. The components of the potentiometric bilirubin sensor were embedded in a paper-based device to provide a sensor that is disposable and easy to use, and thus is suitable for applications at the point-of-care. The paper-based potentiometric bilirubin sensor exhibited a response range of 5.0-0.10u202fmM (sufficient to cover the clinically-relevant concentration of bilirubin in serum). Only 15u202fμL of sample is required for measurement of the concentration of free bilirubin, and the analysis can be performed in less than two minutes.