Three-dimensional porous polymer scaffolds for tissue engineering application

This thesis investigates three-dimensional porous polymer blend scaffolds fabricated using supercritical carbon dioxide combined with solvent etching. These scaffolds with improved pore structures and interconnectivity can be used in regeneration medicine and tissue engineering application.

Multichannel biomedical time series clustering via hierarchical probabilistic latent semantic analysis

Biomedical time series clustering that automatically groups a collection of time series according to their internal similarity is of importance for medical record management and inspection such as bio-signals archiving and retrieval. In this paper, a novel framework that automatically groups a set of unlabelled multichannel biomedical time series according to their internal structural similarity is proposed. Specifically, we treat a multichannel biomedical time series as a document and extract local segments from the time series as words. We extend a topic model, i.e., the Hierarchical probabilistic Latent Semantic Analysis (H-pLSA), which was originally developed for visual motion analysis to cluster a set of unlabelled multichannel time series. The H-pLSA models each channel of the multichannel time series using a local pLSA in the first layer. The topics learned in the local pLSA are then fed to a global pLSA in the second layer to discover the categories of multichannel time series. Experiments on a dataset extracted from multichannel Electrocardiography (ECG) signals demonstrate that the proposed method performs better than previous state-of-the-art approaches and is relatively robust to the variations of parameters including length of local segments and dictionary size. Although the experimental evaluation used the multichannel ECG signals in a biometric scenario, the proposed algorithm is a universal framework for multichannel biomedical time series clustering according to their structural similarity, which has many applications in biomedical time series management.

Characterisation of minimalist co-assembled fluorenylmethyloxycarbonyl self-assembling peptide systems for presentation of multiple bioactive peptides

The nanofibrillar structures that underpin self-assembling peptide (SAP) hydrogels offer great potential for the development of finely tuned cellular microenvironments suitable for tissue engineering. However, biofunctionalisation without disruption of the assembly remains a key issue. SAPS present the peptide sequence within their structure, and studies to date have typically focused on including a single biological motif, resulting in chemically and biologically homogenous scaffolds. This limits the utility of these systems, as they cannot effectively mimic the complexity of the multicomponent extracellular matrix (ECM). In this work, we demonstrate the first successful co-assembly of two biologically active SAPs to form a coassembled scaffold of distinct two-component nanofibrils, and demonstrate that this approach is more bioactive than either of the individual systems alone. Here, we use two bioinspired SAPs from two key ECM proteins: Fmoc-FRGDF containing the RGD sequence from fibronectin and Fmoc-DIKVAV containing the IKVAV sequence from laminin. Our results demonstrate that these SAPs are able to co-assemble to form stable hybrid nanofibres containing dual epitopes. Comparison of the co-assembled SAP system to the individual SAP hydrogels and to a mixed system (composed of the two hydrogels mixed together post-assembly) demonstrates its superior stable, transparent, shear-thinning hydrogels at biological pH, ideal characteristics for tissue engineering applications. Importantly, we show that only the coassembled hydrogel is able to induce in vitro multinucleate myotube formation with C2C12 cells. This work illustrates the importance of tissue engineering scaffold functionalisation and the need to develop increasingly advanced multicomponent systems for effective ECM mimicry.

STATEMENT OF SIGNIFICANCE: Successful control of stem cell fate in tissue engineering applications requires the use of sophisticated scaffolds that deliver biological signals to guide growth and differentiation. The complexity of such processes necessitates the presentation of multiple signals in order to effectively mimic the native extracellular matrix (ECM). Here, we establish the use of two biofunctional, minimalist self-assembling peptides (SAPs) to construct the first co-assembled SAP scaffold. Our work characterises this construct, demonstrating that the physical, chemical, and biological properties of the peptides are maintained during the co-assembly process. Importantly, the coassembled system demonstrates superior biological performance relative to the individual SAPs, highlighting the importance of complex ECM mimicry. This work has important implications for future tissue engineering studies.

Mobile health (mHealth) biomedical imaging paradigm

Technology assisted methods for medical diagnosis and biomedical health monitoring are rapidly shifting from classical invasive methods to handheld-based non-invasive approaches. Biomedical imagining is one of the most prominent practices of non-invasive mechanisms in medical applications. This paper considers the medical imaging schemes for Mobile Health (mHealth) applications and studies the feasibility of future mobile systems for accommodating image informatics capabilities.

Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Wet-Spun Biodegradable Fibers on Conducting Platforms: Novel Architectures for Muscle Regeneration

Novel biosynthetic platforms supporting ex vivo growth of partially differentiated muscle cells in an aligned linear orientation that is consistent with the structural requirements of muscle tissue are described. These platforms consist of biodegradable polymer fibers spatially aligned on a conducting polymer substrate. Long multinucleated myotubes are formed from differentiation of adherent myoblasts, which align longitudinally to the fiber axis to form linear cell-seeded biosynthetic fiber constructs. The biodegradable polymer fibers bearing undifferentiated myoblasts can be detached from the substrate following culture. The ability to remove the muscle cell-seeded polymer fibers when required provides the means to use the biodegradable fibers as linear muscle-seeded scaffold components suitable for in vivo implantation into muscle. These fibers are shown to promote differentiation of muscle cells in a highly organized linear unbranched format in vitro and thereby potentially facilitate more stable integration into recipient tissue, providing structural support and mechanical protection for the donor cells. In addition, the conducting substrate on which the fibers are placed provides the potential to develop electrical stimulation paradigms for optimizing the ex vivo growth and synchronization of muscle cells on the biodegradable fibers prior to implantation into diseased or damaged muscle tissue.

Genetic connectivity between trans-oceanic populations of Capreolia implexa (Gelidiales, Rhodophyta) in cool temperate waters of Australasia and Chile.

Capreolia is a monospecific genus of gelidioid red algae and has been considered to be endemic to Australasia. This is the first report on the occurrence of Capreolia implexa outside of Australasian waters, based on investigations of fresh collections in southern Chile as well as Australia and New Zealand. Thalli are prostrate and form entangled turfs, growing on high intertidal rocks at three locations in Chile. Analyses of rbcL and cox1 revealed that C. implexa was of Australasian origin and also distinct from its relatives. Analyses of 1356. bp of cox1 revealed cryptic diversity, consisting of two genealogical groups within C. implexa; one present in Australia and New Zealand, and the other in Chile and Stewart Island, New Zealand. The extremely low genetic diversity found in C. implexa in Chile and the absence of shared haplotypes between Chile and Australasia suggest genetic bottleneck possibly as a result of colonization after dispersal by rafting from Stewart Island, New Zealand to Chile. © 2014 Elsevier B.V.

Layer-by-layer assembly of silica nanoparticles on 3D fibrous scaffolds : enhancement of osteoblast cell adhesion, proliferation, and differentiation

Silica nanoparticles were applied onto the fiber surface of an interbonded three-dimensional polycaprolactone fibrous tissue scaffold by an electrostatic layer-by-layer self-assembly technique. The nanoparticle layer was found to improve the fiber wettability and surface roughness. Osteoblast cells were cultured on the fibrous scaffolds to evaluate the biological compatibility. The silica nanoparticle coated scaffold showed enhanced cell attachment, proliferation, and alkaline phosphatase activities. The overall results suggested that interbonded fibrous scaffold with silica nanoparticulate coating could be a promising scaffolding candidate for various applications in bone repair and regeneration.

Closed loop deep brain stimulation: an evolving technology

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Automated quantification of neurite outgrowth orientation distributions on patterned surfaces

Objective. We have developed an image analysis methodology for quantifying the anisotropy of neuronal projections on patterned substrates. Approach. Our method is based on the fitting of smoothing splines to the digital traces produced using a non-maximum suppression technique. This enables precise estimates of the local tangents uniformly along the neurite length, and leads to unbiased orientation distributions suitable for objectively assessing the anisotropy induced by tailored surfaces. Main results. In our application, we demonstrate that carbon nanotubes arrayed in parallel bundles over gold surfaces induce a considerable neurite anisotropy; a result which is relevant for regenerative medicine. Significance. Our pipeline is generally applicable to the study of fibrous materials on 2D surfaces and should also find applications in the study of DNA, microtubules, and other polymeric materials.

Thermomechanical properties of Ni-Ti shape memory wires containing nanoscale precipitates induced by stress-assisted ageing.

This paper systematically examines the thermomechanical properties and phase transformation behaviour of slightly Ni-rich Ni-Ti biomedical shape memory wires containing homogeneously distributed nanoscale precipitates induced by stress-assisted ageing. In contrast to previous studies, particular attention is paid to the role of precipitates in impeding twin boundary movement (TBM) and its underlying mechanisms. The size and volume fraction of precipitates are altered by changing the ageing time. The martensitic transformation temperatures increase with prolonged ageing time, whereas the R-phase transformation temperature remains relatively unchanged. The stress-strain behaviour in different phase regions during both cooling and heating is comprehensively examined, and the underlying mechanisms for the temperature- and thermal-history-dependent behaviour are elucidated with the help of the established stress-temperature phase diagram. The effect of precipitates on TBM is explored by mechanical testing at 133K. It is revealed that the critical stress for TBM (σcr) increases with increasing ageing time. There is a considerable increase of 104MPa in σcr in the sample aged at 773K for 120min under 70MPa compared with the solution-treated sample, owing to the presence of precipitates. The Orowan strengthening model of twinning dislocations is insufficient to account for this increase in σcr. The back stress generation is the predominant mechanism for the interactions between precipitates and twin boundaries during TBM that give rise to the increase in σcr. Such results provide new insights into the thermomechanical properties of precipitate containing Ni-Ti biomedical shape memory wires, which are instructive for developing high-performance biomedical shape memory alloys.

Lubricin: a versatile, biological anti-adhesive with properties comparable to polyethylene glycol

Lubricin is a glycoprotein found in articular joints which has been recognized as being an important biological boundary lubricant molecule. Besides providing lubrication, we demonstrate, using a quartz crystal microbalance, that lubricin also exhibits anti-adhesive properties and is highly effective at preventing the non-specific adsorption of representative globular proteins and constituents of blood plasma. This impressive anti-adhesive property, combined with lubricin's ability to readily self-assemble to form dense, highly stable telechelic polymer brush layers on virtually any substrates, and its innate biocompatibility, makes it an attractive candidate for anti-adhesive and anti-fouling coatings. We show that coatings of lubricin protein are as effective as, or better than, self-assembled monolayers of polyethylene glycol over a wide range of pH and that this provides a simple, versatile, highly stable, and highly effective method of controlling unwanted adhesion to surfaces.

Evaluation of neck muscle size: long-term reliability and comparison of methods

Although it is important for prospective studies, the reliability of quantitative measures of cervical muscle size on magnetic resonance imaging is not well established. The aim of the current work was to assess the long-term reliability of measurements of cervical muscle size. In addition, we examined the utility of selecting specific sub-regions of muscles at each vertebral level, averaging between sides of the body, and pooling muscles into larger groups. Axial scans from the base of skull to the third thoracic vertebra were performed in 20 healthy male subjects at baseline and 1.5 years later. We evaluated the semi-spinalis capitis, splenius capitis, spinalis cervicis, longus capitis, longus colli, levator scapulae, sternocleidomastoid, anterior scalenes and middle with posterior scalenes. Bland-Altman analysis showed all measurements to be repeatable between testing-days. Reliability was typically best when entire muscle volume was measured (co-efficients of variation (CVs): 3.3-8.1% depending on muscle). However, when the size of the muscle was assessed at specific vertebral levels, similar measurement precision was achieved (CVs: 2.7-7.6%). A median of 4-6 images were measured at the specific vertebral levels versus 18-37 images for entire muscle volume. This would represent considerable time saving. Based on the findings we also recommend measuring both sides of the body and calculating an average value. Pooling specific muscles into the deep neck flexors (CV: 3.5%) and neck extensors (CV: 2.7%) can serve to reduce variability further. The results of the current study help to establish outcome measures for interventional studies and for sample size estimation.

Fuzzy system with tabu search learning for classification of motor imagery data

This paper introduces an approach to classify EEG signals using wavelet transform and a fuzzy standard additive model (FSAM) with tabu search learning mechanism. Wavelet coefficients are ranked based on statistics of the Wilcoxon test. The most informative coefficients are assembled to form a feature set that serves as inputs to the tabu-FSAM. Two benchmark datasets, named Ia and Ib, downloaded from the brain-computer interface (BCI) competition II are employed for the experiments. Classification performance is evaluated using accuracy, mutual information, Gini coefficient and F-measure. Widely-used classifiers, including feedforward neural network, support vector machine, k-nearest neighbours, ensemble learning Adaboost and adaptive neuro-fuzzy inference system, are also implemented for comparisons. The proposed tabu-FSAM method considerably dominates the competitive classifiers, and outperforms the best performance on the Ia and Ib datasets reported in the BCI competition II.

A new design concept for knitted external vein-graft support mesh

Autologous vein-graft failure significantly limits the long-term efficacy of coronary artery bypass procedures. The major cause behind this complication is biomechanical mismatch between the vein and coronary artery. The implanted vein experiences a sudden increase (10-12 fold) in luminal pressures. The resulting vein over-distension or 'ballooning' initiates wall thickening phenomenon and ultimate occlusion. Therefore, a primary goal in improving the longevity of a coronary bypass procedure is to inhibit vein over-distension using mechanical constriction. The idea of using an external vein-graft support mesh has demonstrated sustained benefits and wide acceptance in experimental studies. Nitinol based knitted structures have offered more promising mechanical features than other mesh designs owing to their unique loosely looped construction. However, the conventional plain knit construction still exhibits limitations (radial compliance, deployment ease, flexibility, and bending stresses) which limit this design from proving its real clinical advantage. The new knitted mesh design presented in this study is based on the concept of composite knitting utilising high modulus (nitinol and polyester) and low modulus (polyurethane) material components. The experimental comparison of the new design with a plain knit design demonstrated significant improvement in biomechanical (compliance, flexibility, extensibility, viscoelasticity) and procedural (deployment limit) parameters. The results are indicative of the promising role of new mesh in restoring the lost compliance and pulsatility of vein-graft at high arterial pressures. This way it can assist in controlled vein-graft remodelling and stepwise restoration of vein mechanical homoeostasis. Also, improvement in deployment limit parameter offers more flexibility for a surgeon to use a wide range of vein diameters, which may otherwise be rendered unusable for a plain knit mesh.