1,721,032 research outputs found
Influences of topography and composition on hepatocytes within electrospun polycaprolactone scaffolds for liver tissue engineering
Full text linkSevere liver disease is one of the most common causes of death globally and its mortality has been rising since the 1970s. A quarter of the global population is predicted to have non-alcoholic fatty liver disease, which increases their risk of developing chronic conditions like fibrosis and hepatocellular carcinoma (HCC). Currently, whole organ transplantation is the only definitive cure for end-stage liver disease, however, the need for donor organs far outweighs demand. Recently liver tissue engineering is starting to show promise for alleviating the burden on liver disease patients and healthcare providers. It is essential to find effective pharmaceutical and regenerative therapies that can slow or halt disease progression. Achieving this goal involves using in vitro methods to produce liver models for testing target and drug molecules, expanding cells with regenerative capacity, and creating bioartificial liver devices. In recent decades, in vitro hepatocyte culture methods have evolved from 2D culture to 3D organoids and scaffold cultures that offer a biomimetic environment and elicit phenotypic responses from hepatocytes. Electrospinning is a well-known method to fabricate a nanofibre scaffold which mimics the natural extracellular matrix (ECM) which can support cell growth.
This thesis has sought to optimise electrospun polycaprolactone (PCL) scaffolds for the culture of hepatocytes, with a focus on topography and composition. Three methods were utilized: 1) investigation of surface topography of electrospun PCL scaffolds on hepatocytes; 2) incorporation of decellularized rat liver extracellular matrix (dECM) into topographical featured PCL scaffolds and assess its impact on hepatocytes; 3) incorporation of human dECM into topographical featured PCL scaffolds and assess its impact on hepatocytes. All fabricated scaffolds were conducted for physical and chemical analyses and cultured with immortalised hepatic cell line HepG2 or mouse primary hepatocytes MPHs. The biological influence of the scaffolds on cellular behaviours was assessed through proliferation assays, immunohistochemistry, osmium staining and RT-qPCR gene expression analysis. Our results show that fibre surface topography have an influence on cell attachment, proliferation, morphology and functionality. Small surface nanotopographies at around 0.37 μm show to significantly increase the attachment and proliferative activities of HepG2 compared to large microtopographies (2 μm). The incorporation of rat and human dECM into topographically modified fibres both kept the morphological consistency (all randomly oriented and have similar fibre diameters in each study). Both rat and human dECM-containing scaffolds have promoted the HepG2 to grow as a densely packed monolayer-like structure, and showed an increasing trend of albumin gene expression. All topographically modified scaffolds or dECM-contained hybrid scaffolds exhibit good compatibility and have the ability to maintain HepG2 steady growth compared to smooth PCL fibres. Primary cells displayed sustained bioactivity after three days of culture in all scaffolds, with the results showing the trends of higher DNA content and higher expression of fibronectin observed in these cultured on the hybrid scaffolds. These studies show that the topography and composition can be utilized to modulate the physiological activity of electrospun PCL scaffolds and have a measurable impact on hepatocyte cultures. Our method provides a reproducible approach and emphasizes the synergism of topographical stimuli and biochemical cues on electrospun scaffolds, which have wide-ranging application prospects in in vitro hepatic microenvironments
Wearable and Stretchable Strain Sensors: Materials, Sensing Mechanisms, and Applications
Full text linkRecent advances in the design and implementation of wearable resistive, capacitive, and optical strain sensors are summarized herein. Wearable and stretchable strain sensors have received extensive research interest due to their applications in personalized healthcare, human motion detection, human–machine interfaces, soft robotics, and beyond. The disconnection of overlapped nanomaterials, reversible opening/closing of microcracks in sensing films, and alteration of the tunneling resistance have been successfully adopted to develop high-performance resistive-type sensors. On the other hand, the sensing behavior of capacitive-type and optical strain sensors is largely governed by their geometrical changes under stretching/releasing cycles. The sensor design parameters, including stretchability, sensitivity, linearity, hysteresis, and dynamic durability, are comprehensively discussed. Finally, the promising applications of wearable strain sensors are highlighted in detail. Although considerable progress has been made so far, wearable strain sensors are still in their prototype stage, and several challenges in the manufacturing of integrated and multifunctional strain sensors should be yet tackled
Improving sensor performance by characterising the selectivity in vapour etching
Full text linkThe vapour etching of sacrificial layers is often a critical process in the fabrication
of micro/nano electromechanical systems (MEMS/NEMS) sensors. Compared to wet
etch methods, it has several advantages. Smaller devices can be fabricated because
stiction does not occur, sample cross-contamination can be avoided, and it is safer to
operate. However, in contrast to wet etching, signi cantly lower etch selectivities are
reported in the literature and observed by industry practitioners, limiting both this
release method’s and MEMS/NEMS sensors potential.
This work aims to improve the etch selectivity for the most commonly used vapour
etch processes, the silicon etching with xenon di uoride (XeF2) and hydrogen uoride (HF) etching of silicon dioxide.
A novel test structure and measurement methodology that allows the accurate selectivity determination for a number of materials and resembles MEMS fabrication
conditions was developed, fabricated and characterised.
The selectivity of XeF2 vapour etch processes were characterised with this methodology. It was observed that materials such as silicon nitride, which are commonly inert
to XeF2 etched when located close to the sacri cial layer, and methods to improve the
selectivity were evaluated. Firstly, it was observed that reducing the processing temperature from 25 to 10 °C increases the silicon (Si) to silicon nitride (SiN) selectivity
by 68 %. Secondly, the Si: PECVD SiN selectivity improved by an order of magnitude
and the Si: LPCVD SiN selectivity between 200 % and 600 % when moderate amounts
of hydrogen were added to the processing gas mixture.
In contrast to xenon di uoride vapour etching, a catalyst (water or alcohol) and the
formation of a thin liquid layer on the sample is required to facilitate hydrogen uoride vapour etching. To improve the limited process control resulting from the complex condensation phenomena, a novel model, which calculates the partial pressures
of the individual gas components to establish vapour pressure within the gas phase,
was developed and characterised.
It was observed that vapour HF etching behaves similar to wet HF etching under these
controlled conditions. The silicon dioxide to silicon nitride selectivity was demonstrated to improve by 150 % when reducing the processing temperature from 20 to 5
°C and by 166 % when increasing the liquid lm’s HF concentration from 20 – 90 %.
The methods developed in this work substantially improve the vapour etch selectivity and enable the development of smaller, more sensitive and more robust micro
and nanosensors
3D Electrospinning: the combination of electrospinning and 3D-printing for the fast fabrication of designed 3D polymeric macrostructures made of nanofibres
No full textNanofibrous structures, due to their unique morphology boasting a high surface areato-volume ratio, make them interesting in several research fields. Added to that, recent
studies have highlighted the important benefits of assembling 3D structures with
nanofibrous features. For example, 3D scaffolds made of nanofibres have been shown
to have better cell attachment and growth, because of their close resemblance to the
natural extracellular matrix. 3D nanofibrous structures have also been used in high
filtration processes.
Electrospinning is a good candidate for building these 3D nanofibrous structures. The
high versatility of electrospinning allows it to change the morphology of the electrospun
fibres easily (porosity, diameter, surface roughness, fibres alignment, etc…). The
nature of the polymer used in electrospinning is flexible as well, and with the existing
possibility for further functionalizing electrospun fibres, electrospinning is applicable to
a wide range of research fields. Furthermore, several methods of inducing 3D build-up
via electrospinning have been investigated, however, these methods have several
disadvantages such as being time-consuming, made of several steps, requiring an
extra support material, or having no control over the shape of the final 3D structures.
In this thesis, a device combining the versatility of electrospinning with the
manoeuvrability of 3D printing is studied. By inserting specific additives to a polymer
solution, self-assembly of 3D structures via electrospinning is possible. The precise
control of the movement of the nozzle head during electrospinning, as well as the
setting of the collector height allow to direct the position of the deposition area during
the whole electrospinning process.
By combining these two features together, it is possible to fabricate a designed 3D
polymeric macrostructure made of nanofibres, from a simple computer-aided design
(CAD) file. Thus, this technology is named “3D electrospinning”.
The first aspect of this thesis is to have an in-depth look at the formation mechanism
of 3D electrospun structures. The process parameters of 3D electrospinning have been
identified and investigated to better understand the formation mechanism of the 3D
build-up for polystyrene (PS), the model polymer. It is shown that the crystal phase of
the polymer itself, the viscosity and the conductivity of the polymer solution have no
influence on the 3D build-up of the electrospun structures. It was instead shown that
the rapid solidification of the fibres as well as the in-situ charge induction and
polarization of the fibres are inducing the 3D build-up. Overall, it is possible to build a
3~4 cm high macrostructure in a single step in 10 minutes of electrospinning.
A thorough study of the experimental parameters of 3D electrospinning allows to
optimise the shaping of the 3D electrospun structures, in terms of wall resolution and
fibres’ morphology. It is shown that the improper adjustment of any parameters such
as polymer concentration, applied voltage, working distance, flow rate or nozzle
moving speed can have detrimental effects on the 3D build-up and instead leads to an
electrospun flat 2D mat. After identifying the optimal experimental parameters, several
shapes such as triangle, square, star or smiley face, are electrospun to showcase the
versatility of the 3D electrospinning process. Other polymers such as polyacrylonitrile
(PAN) and polyvinylpyrrolidone (PVP) are then 3D electrospun to extend the range of
usable polymers, and thus potential applications, for 3D electrospinning. The
differences in shape induced by each polymer are identified.
Different types of electrodes are then used to change the electric field profile and alter
the path of the electrospun jet. Base electrodes and steering electrodes are shown to
have detrimental effects on the 3D build-up leading to either poor drying of the fibres
or poor shaping of the 3D structures. Guiding electrodes (electrode at the collector
level) were able to further enhance the shaping of the 3D electrospun structures, with
an increased wall resolution and no noticeable drawback. However, this beneficial
effect was only shown for polystyrene. A pillar support was used as a guiding electrode
to force the fabrication of an electrospun 3D structure with radial alignment. The effect
of the pillar height, pillar thickness, applied voltage and working distance on the 3D
structure and fibres alignment is shown.
Finally, the long-term stability and the mechanical stability of the 3D electrospun
structures have been investigated. While both PS and PAN structures show high shelflife in ambient conditions, only 3D PS structures demonstrate some shape recovery
after compression.
Upscaling of the 3D structures was then achieved with both the 3D electrospinning
device and a nozzle-free electrospinning setup. Similar to extrusion-based 3D printing,
it is possible to raise the working distance during 3D electrospinning to increase the
final height of the 3D structure. 3D electrospinning with a nozzle-free electrospinning
setup is possible via precise control of the rotation speed during 3D build-up. This
opens up the possibility to fabricate electrospun 3D structures on a commercial scale.
Carbonization of 3D PAN structures is also demonstrated, to fabricate carbon fibrous
structures with 3D features, which can have applications in energy-related fields.
The work conducted in this thesis has successfully expanded upon the field of 3D
material fabrication. 3D electrospinning is a simple, cost-effective and fast process to
build designed 3D structures. It is a versatile process not limited to a single type of
polymer. As such, 3D electrospinning is a viable technique for several applications. 3D
PS and 3D PVP could both be used as a cell culture material. 3D PAN, which is a
typical precursor for carbon fibres, could be used as an electrode material for Lithiumion batteries
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Fabrication of tubular constructs using hybrid extrusion printing and electrospinning for vascular tissue engineering applications
Full text linkCardiovascular disease is the leading cause of mortality in the world, with the number
of deaths rising every year. Coronary artery disease, peripheral artery disease,
aneurysm, and strokes are the most prominent forms of vascular diseases. Bypass
surgery is one of the techniques performed to treat these vascular diseases, which
involves the re-routing of blood flow around the blocked arterial site using a vascular
graft. Autologous grafts, such as saphenous vein and internal mammary artery, remain
a gold standard for bypass grafting procedures. However, the removal of autologous
grafts often results in the donor site morbidity. In some cases, the grafts are
unavailable due to previous harvest or poor quality. Synthetic grafts represent an
alternate option, however, they usually fail when used as small diameter bypass grafts.
The mismatch between the mechanical properties of synthetic grafts and native
arteries is the major cause of failure of these synthetic grafts made from PET and
ePTFE. Therefore, there is an urgent and high demand to fabricate a vascular conduit
having biomechanical behaviour similar to that of the native arteries.
In this thesis, a new hybrid extrusion printing and electrospinning technique is
presented to fabricate vascular grafts. A commercially available Creality3D Ender 3D
printer was modified into a hybrid setup having a vertical mandrel, an extrusion printing
head, and electrospinning heads. The setup is capable of fabricating layered structure
using hydrogel and electrospun nanofibres. The gelatin methacryloyl (gelMA) hydrogel
was selected for printing tubular constructs as it is widely used in the literature to
encapsulate cells for bioprinting. Polycaprolactone (PCL) and Poly (L-lactide-co-ε-
caprolactone) (PLCL) polymers were used to produce electrospun nanofibres for the
reinforcement of hydrogel conduits. The setup was successfully tested to print grafts
around the rotating mandrel.
Bioprinting is an attractive technique to print tissues using hydrogels. However,
printing of long tubular constructs from hydrogels remains a challenge. Additive-lathe
printing method offers a solution to print grafts with high aspect ratios but printing
hydrogels around the horizontal rods often leads to sagging, which results in the
non-uniform wall thickness and subsequently variable mechanical properties.
A new approach of printing around the vertical mandrel was used to fabricate gelMA grafts
having uniform wall thickness. The printing parameters were selected to achieve the
overlapping of two consecutive printed filaments, which resulted in the better bonding
of filaments and good quality tubular constructs were fabricated. The tensile testing
results revealed that the anisotropic properties of printed gelMA grafts were similar to
those observed in the natural blood vessels. Moreover, no leakage was detected in
the printed gelMA tubular constructs during the burst pressure measurement. Thus, a
vertical additive-lathe printing method offers an attractive technique to print long
vascular grafts using hydrogels.
The burst pressure of the gelMA grafts printed on vertical additive-lathe printing setup
was found to be lower than the normal haemodynamic blood pressures. Therefore, a
reinforcement is required. A layer of electrospun nanofibres was collected over the
printed hydrogel constructs to improve the mechanical performance. Various blends
of Polycaprolactone (PCL) and poly(L-lactide-co-ε-caprolactone) (PLCL) polymer
solutions were used to produce electrospun nanofibres. The printed bi-layered
vascular grafts showed mechanical properties close to that of the native arteries. The
tensile strength of the 12% gelMA constructs reinforced by 100/0 PCL/PLCL blend
fibres was found to be greater than 3 MPa, which falls in the range of tensile strength
value of native arteries (0.5 – 3 MPa for coronary arteries and 1.5 – 4 MPa for radial
and mammary arteries). The fabricated vascular grafts showed a burst pressure of
more than 2000 mmHg, which is within the range of burst pressure values for the
human saphenous vein (1250 – 2476 mmHg) and radial artery (2001 – 2476 mmHg).
Moreover, the compliance values of gelMA constructs reinforced by 100/0 PCL/PLCL
(6.85 ± 1.01 %/100mmHg) and 75/25 PCL/PLCL (17.13 ± 7.35 %/100mmHg) were
found to be similar to the muscular arteries (6.03 ± 3.39 %/100mmHg) and elastic
arteries (16.21 ± 3.81 %/100mmHg), respectively. The cytocompatibility assessment
showed that gelMA presented a bioactive surface for the endothelial cells to survive
and grow.
The newly developed hybrid setup has been utilized to fabricate fibre-reinforced
vascular grafts. The mechanical performance of these constructs was found to be
similar to that of native arteries. Also, PCL/PLCL fibres showed good cellular metabolic
activity and gelMA surfaces were biocompatible for the HUVECs to grow. Thus, the
presented fabrication method has a great potential to fabricate vascular grafts having
biomechanical properties similar to that of natural blood vessels
Electrospinning for skin tissue engineering and drug-eluting antimicrobial biomaterials
Full text linkA critical challenge in the design of biomaterials for tissue engineering relies on the development of tissue-specific biomimetic scaffolds capable of replacing cell-matrix interactions required for the repair of injured tissues. Further, such biomaterials with the additional capacity to prevent bacteria contamination can resolve issues surrounding surgical prosthesis infection. Fibrous micro- and nanostructures are extensively researched in tissue engineering due to their intrinsic similarities to decellularised human tissues. Among the several fibre-forming processes, electrospinning has drawn much attention due to its ability to produce scaffolds that morphologically resemble the native extracellular matrix (ECM) of human tissues.
Electrospinning is a versatile method that uses electrohydrodynamic principles to produce fibres with diameters ranging from microns to tens of nanometres. By varying the chemistry and morphology of the fibres, it is feasible to attain different physiological and mechanical responses. The wide array of raw natural and synthetic materials – including polymers and complex molecules – that can be used to electrospin fibres can resolve well-documented problems associated with the inferiority of synthetic biomaterials and the limitations of biological tissues.
In this thesis, electrospinning is utilised to contribute to the engineering of advanced ECM-mimicking biomaterials. The work will focus on (1) improving the physicochemical and mechanical responses of skin substitutes and (2) preventing mesh-associated surgical site infection.
The initial study of this thesis presents the design and construction of a nozzle-free electrospinning device, which is an economically viable method of scaling-up fibre production output. The equipment is then used to fabricate elastic skin-like composite nanofibres consisting of poly(vinylpyrrolidone) (PVP) and poly(glycerol sebacate) (PGS). The findings indicate that the mechanical properties of the electrospun mats could be tuned by varying the concentration of PGS and the molecular weight of PVP within the blends. Photocrosslinking the fibres prevented the rapid degradation of the composite mats due to the hydrophilic nature of PVP, making it feasible to assess the biological responses of the construct in vitro, displaying good viability and proliferation of human dermal fibroblasts. This study provides a different approach towards the development of skin substitutes, based on the fact that mechanical stimuli influence the ability of dermal cells to adapt and reconstruct the ECM at an injured site; being able to adjust the mechanics to those of different anatomical sites of the body can have a positive effect on the overall outcome of a healing wound.
Synthetic biomaterials tend to present suboptimal cell growth and proliferation, with many studies linking this phenomenon to the hydrophobicity of such surfaces. This thesis continues with the development of a protocol for silk fibroin extraction from Bombyx mori cocoons, which achieved significantly increased yields of the protein in a third of the time required by the conventional molecular cut-off extraction approach. The extracted silk fibroin was then used to produce electrospun membranes consisting of poly(caprolactone) (PCL) blended with variant forms of PGS. The main aim of this work was the development of fibre mats with tuneable hydrophobicity/hydrophilicity properties, depending on the esterification degree and concentration of PGS within each composite. By altering the surface properties of the electrospun membranes, the trinary composite biomaterial presented improved fibroblast attachment behaviour and optimal growth in comparison to PCL-only fibrous mats.
The study continued with the development of an ultralight-weight nanostructured bicomponent antimicrobial construct with a similar microstructure to biologic meshes, which preserved the required mechanical integrity of synthetic mesh materials. A core/shell nanofibrous structure was developed, consisting of nylon-6 in the core and chitosan/polyethylene oxide in the shell. The bicomponent fibre structure comprised a binary antimicrobial system incorporating 5-chloro-8-quinolinol in the chitosan-shell, with the sustained release of polyhexamethylene biguanide from the nylon-6 core of the fibres. The antimicrobial nanofibres were found to elicit a robust bactericidal response, in vitro, against the two most commonly occurring pathogenic bacteria in deep incisional surgical site infections; Staphylococcus aureus and Pseudomonas aeruginosa. The results of this study advocate that the bicomponent nanofibres developed can be a promising alternative to biologic meshes, employed for hernia repair today, due to similar architecture and mechanics, but at the same time capable of actively protecting the patient from subsequent mesh-associated infections, thus tackling this life-threatening postoperative complication.
Overall, the work in this thesis has expanded upon the fields of skin tissue engineering and drug-eluting antimicrobial biomaterials, potentially guiding new areas of research
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