ORCID Profile
0000-0003-0423-4560
Current Organisations
University of Queensland
,
Queensland University of Technology
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Biomedical Engineering not elsewhere classified | Biomedical Engineering
Expanding Knowledge in Engineering | Expanding Knowledge in the Biological Sciences |
Publisher: MDPI AG
Date: 08-06-2022
DOI: 10.3390/JFB13020075
Abstract: The fabrication of patient-specific scaffolds for bone substitutes is possible through extrusion-based 3D printing of calcium phosphate cements (CPC) which allows the generation of structures with a high degree of customization and interconnected porosity. Given the brittleness of this clinically approved material, the stability of open-porous scaffolds cannot always be secured. Herein, a multi-technological approach allowed the simultaneous combination of CPC printing with melt electrowriting (MEW) of polycaprolactone (PCL) microfibers in an alternating, tunable design in one automated fabrication process. The hybrid CPC+PCL scaffolds with varying CPC strand distance (800–2000 µm) and integrated PCL fibers featured a strong CPC to PCL interface. While no adverse effect on mechanical stiffness was detected by the PCL-supported scaffold design the microfiber integration led to an improved integrity. The pore distance between CPC strands was gradually increased to identify at which critical CPC porosity the microfibers would have a significant impact on pore bridging behavior and growth of seeded cells. At a CPC strand distance of 1600 µm, after 2 weeks of cultivation, the incorporation of PCL fibers led to pore coverage by a human mesenchymal stem cell line and an elevated proliferation level of murine pre-osteoblasts. The integrated fabrication approach allows versatile design adjustments on different levels.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 10-07-2020
DOI: 10.1038/S41598-020-67945-Z
Abstract: Craniofacial prostheses are commonly used to restore aesthetics for those suffering from malformed, damaged, or missing tissue. Traditional fabrication is costly, uncomfortable for the patient, and laborious involving several hours of hand-crafting by a prosthetist, with the results highly dependent on their skill level. In this paper, we present an advanced manufacturing framework employing three-dimensional scanning, computer-aided design, and computer-aided manufacturing to efficiently fabricate patient-specific ear prostheses. Three-dimensional scans were taken of ears of six participants using a structured light scanner. These were processed using software to model the prostheses and 3-part negative moulds, which were fabricated on a low-cost desktop 3D printer, and cast with silicone to produce ear prostheses. The average cost was approximately $3 for consumables and $116 for 2 h of labour. An injection method with smoothed 3D printed ABS moulds was also developed at a cost of approximately $155 for consumables and labour. This contrasts with traditional hand-crafted prostheses which range from $2,000 to $7,000 and take around 14 to 15 h of labour. This advanced manufacturing framework provides potential for non-invasive, low cost, and high-accuracy alternative to current techniques, is easily translatable to other prostheses, and has potential for further cost reduction.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.ACTBIO.2021.09.042
Abstract: Tissue engineering involves the seeding of cells into a structural scaffolding to regenerate the architecture of damaged or diseased tissue. To effectively design a scaffold, an understanding of how cells collectively sense and react to the geometry of their local environment is needed. Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro scaffold model to study cellular spatial-temporal kinetics. These scaffolds were paired with custom computer vision algorithms to investigate cell nuclei, cell membrane actin and scaffold fibres over different pore sizes (200-600 µm) and time points (28 days). We find that cells proliferated much faster in the smaller (200 µm) pores which halved the time until confluence versus larger (500 and 600 µm) pores. Our analysis of stained actin fibres revealed that cells were highly aligned to the fibres and the leading edge of the pore filling front, and we found that cells behind the leading edge were not aligned in any particular direction. This study provides a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model to inform the design of more effective synthetic tissue engineering scaffolds for tissue regeneration. STATEMENT OF SIGNIFICANCE: Advances in the development of melt electro-writing have allowed micron and submicron polymeric fibres to be accurately printed into porous, complex and three-dimensional structures. By using melt electrowriting, we created a geometrically relevant in vitro model to study cellular spatial-temporal kinetics to provide a systematic understanding of cellular spatial temporal kinetics within a 3D in vitro model. The insights presented in this work help to inform the design of more effective synthetic tissue engineering scaffolds by reducing cell culture time which is valuable information for the implant or lab-grown-meat industries.
Publisher: Mary Ann Liebert Inc
Date: 02-2017
Publisher: IOP Publishing
Date: 20-04-2022
Abstract: Tissue biomanufacturing aims to produce lab-grown stem cell grafts and biomimetic drug testing platforms but remains limited in its ability to recapitulate native tissue mechanics. The emerging field of soft robotics aims to emulate dynamic physiological locomotion, representing an ideal approach to recapitulate physiologically complex mechanical stimuli and enhance patient-specific tissue maturation. The kneecap’s femoropopliteal artery (FPA) represents a highly flexible tissue across multiple axes during blood flow, walking, standing, and crouching positions, and these complex biomechanics are implicated in the FPA’s frequent presentation of peripheral artery disease. We developed a soft pneumatically actuated (SPA) cell culture platform to investigate how patient-specific FPA mechanics affect lab-grown arterial tissues. Silicone hyperelastomers were screened for flexibility and biocompatibility, then additively manufactured into SPAs using a simulation-based design workflow to mimic normal and diseased FPA extensions in radial, angular, and longitudinal dimensions. SPA culture platforms were seeded with mesenchymal stem cells, connected to a pneumatic controller, and provided with 24 h multi-axial exercise schedules to demonstrate the effect of dynamic conditioning on cell alignment, collagen production, and muscle differentiation without additional growth factors. Soft robotic bioreactors are promising platforms for recapitulating patient-, disease-, and lifestyle-specific mechanobiology for understanding disease, treatment simulations, and lab-grown tissue grafts.
Publisher: Springer Science and Business Media LLC
Date: 05-01-2023
DOI: 10.1038/S41598-022-27354-W
Abstract: Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress ergence (WSSD) contributed to the growth of a daughter sac.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 09-2019
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.BIOMATERIALS.2018.08.020
Abstract: Traditional culture systems for human erythropoiesis lack microenvironmental niches, spatial marrow gradients and dense cellularity rendering them incapable of effectively translating marrow physiology ex vivo. Herein, a bio-inspired three-dimensional (3D) perfusion bioreactor was engineered and inoculated with unselected single donor umbilical cord blood mononuclear cells (CBMNCs). Functional stromal and hematopoietic environments supporting long-term erythropoiesis were generated using defined medium supplemented only with stem cell factor (SCF) and erythropoietin (EPO) at near physiological concentrations. Quantitative 3D image analyses spatiotemporally mapped 21 multi-lineal cell distributions and interactions within multiple microenvironments that secreted extracellular matrix proteins and at least 16 endogenous hematopoietic and stromal growth factors. Tissue-like culture densities (≥2∙10
Publisher: CRC Press
Date: 03-09-2018
Publisher: Elsevier BV
Date: 03-2021
Publisher: Wiley
Date: 21-08-2023
DOI: 10.1002/JEMT.24400
Abstract: The femoropopliteal artery (FPA) is a long, flexible vessel that travels down the anteromedial compartment of the thigh as the femoral artery and then behind the kneecap as the popliteal artery. This artery undergoes various degrees of flexion, extension, and torsion during normal walking movements. The FPA is also the most susceptible peripheral artery to atherosclerosis and is where peripheral artery disease manifests in 80% of cases. The connection between peripheral artery location, its mechanical flexion, and its physiological or pathological biochemistry has been investigated for decades however, histochemical methods remain poorly leveraged in their ability to spatially correlate normal or abnormal extracellular matrix and cells with regions of mechanical flexion. This study generates new histological image processing pipelines to quantitate tissue composition across high‐resolution FPA regions‐of‐interest or low‐resolution whole‐section cross‐sections in relation to their anatomical locations and flexions during normal movement. Comparing healthy ovine femoral, popliteal, and cranial‐tibial artery sections as a pilot, substantial arterial contortion was observed in the distal popliteal and cranial tibial regions of the FPA which correlated with increased vascular smooth muscle cells and decreased elastin content. These methods aim to aid in the quantitative characterization of the spatial distribution of extracellular matrix and cells in large heterogeneous tissue sections such as the FPA. Large‐format histology preserves artery architecture. Elastin and smooth muscle content is correlated with distance from heart and contortion during flexion. Cell and protein analyses are sensitive to sectioning plane and image magnification.
Publisher: Mary Ann Liebert Inc
Date: 2022
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.ULTRASMEDBIO.2021.10.013
Abstract: Three-dimensional imaging and advanced manufacturing are being applied in health care research to create novel diagnostic and surgical planning methods, as well as personalised treatments and implants. For ear reconstruction, where a cartilage-shaped implant is embedded underneath the skin to re-create shape and form, volumetric imaging and segmentation processing to capture patient anatomy are particularly challenging. Here, we introduce 3-D ultrasound (US) as an available option for imaging the external ear and underlying auricular cartilage structure, and compare it with computed tomography (CT) and magnetic resonance imaging (MRI) against micro-CT (µCT) as a high-resolution reference (gold standard). US images were segmented to create 3-D models of the auricular cartilage and compared against models generated from µCT to assess accuracy. We found that CT was significantly less accurate than the other methods (root mean square [RMS]: 1.30 ± 0.5 mm) and had the least contrast between tissues. There was no significant difference between MRI (RMS: 0.69 ± 0.2 mm) and US (0.55 ± 0.1 mm). US was also the least expensive imaging method at half the cost of MRI. These results unveil a novel use of ultrasound imaging that has not been presented before, as well as support its more widespread use in biofabrication as a low-cost imaging technique to create patient-specific 3D models and implants.
Publisher: Springer Science and Business Media LLC
Date: 07-2021
DOI: 10.1038/S41598-021-93227-3
Abstract: This paper proposes a fully automatic method to segment the inner boundary of the bony orbit in two different image modalities: magnetic resonance imaging (MRI) and computed tomography (CT). The method, based on a deep learning architecture, uses two fully convolutional neural networks in series followed by a graph-search method to generate a boundary for the orbit. When compared to human performance for segmentation of both CT and MRI data, the proposed method achieves high Dice coefficients on both orbit and background, with scores of 0.813 and 0.975 in CT images and 0.930 and 0.995 in MRI images, showing a high degree of agreement with a manual segmentation by a human expert. Given the volumetric characteristics of these imaging modalities and the complexity and time-consuming nature of the segmentation of the orbital region in the human skull, it is often impractical to manually segment these images. Thus, the proposed method provides a valid clinical and research tool that performs similarly to the human observer.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-10-2021
Publisher: Elsevier BV
Date: 11-2021
Publisher: Wiley
Date: 06-10-2020
DOI: 10.1002/BIT.27176
Abstract: Bioprinting is the assembly of three-dimensional (3D) tissue constructs by layering cell-laden biomaterials using additive manufacturing techniques, offering great potential for tissue engineering and regenerative medicine. Such a process can be performed with high resolution and control by personalized or commercially available inkjet printers. However, bioprinting's clinical translation is significantly limited due to process engineering challenges. Upstream challenges include synthesis, cellular incorporation, and functionalization of "bioinks," and extrusion of print geometries. Downstream challenges address sterilization, culture, implantation, and degradation. In the long run, bioinks must provide a microenvironment to support cell growth, development, and maturation and must interact and integrate with the surrounding tissues after implantation. Additionally, a robust, scaleable manufacturing process must pass regulatory scrutiny from regulatory bodies such as U.S. Food and Drug Administration, European Medicines Agency, or Australian Therapeutic Goods Administration for bioprinting to have a real clinical impact. In this review, recent advances in inkjet-based 3D bioprinting will be presented, emphasizing on biomaterials available, their properties, and the process to generate bioprinted constructs with application in medicine. Current challenges and the future path of bioprinting and bioinks will be addressed, with emphasis in mass production aspects and the regulatory framework bioink-based products must comply to translate this technology from the bench to the clinic.
Publisher: Imperial College London
Date: 2017
DOI: 10.25560/67762
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 07-12-2017
DOI: 10.1002/AIC.16042
Publisher: Wiley
Date: 08-07-2022
Abstract: Engineered tissues provide an alternative to graft material, circumventing the use of donor tissue such as autografts or allografts and non‐physiological synthetic implants. However, their lack of vasculature limits the growth of volumetric tissue more than several millimeters thick which limits their success post‐implantation. Perfused bioreactors enhance nutrient mass transport inside lab‐grown tissue but remain poorly customizable to support the culture of personalized implants. Here, a multiscale framework of computational fluid dynamics (CFD), additive manufacturing, and a perfusion bioreactor system are presented to engineer personalized volumetric tissue in the laboratory. First, microscale 3D printed scaffold pore geometries are designed and 3D printed to characterize media perfusion through CFD and experimental fluid testing rigs. Then, perfusion bioreactors are custom‐designed to combine 3D printed scaffolds with flow‐focusing inserts in patient‐specific shapes as simulated using macroscale CFD. Finally, these computationally optimized bioreactor‐scaffold assemblies are additively manufactured and cultured with pre‐osteoblast cells for 7, 20, and 24 days to achieve tissue growth in the shape of human calcaneus bones of 13 mL volume and 1 cm thickness. This framework enables an intelligent model‐based design of 3D printed scaffolds and perfusion bioreactors which enhances nutrient transport for long‐term volumetric tissue growth in personalized implant shapes. The novel methods described here are readily applicable for use with different cell types, biomaterials, and scaffold microstructures to research therapeutic solutions for a wide range of tissues.
Publisher: Frontiers Media SA
Date: 08-09-2022
Publisher: Figshare
Date: 2016
Publisher: American Chemical Society (ACS)
Date: 13-03-2012
DOI: 10.1021/CG201190C
Publisher: Elsevier BV
Date: 09-2015
Publisher: Unpublished
Date: 2010
Publisher: Elsevier BV
Date: 08-2023
Publisher: Georg Thieme Verlag KG
Date: 25-06-2015
Publisher: Elsevier BV
Date: 10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 13-03-2020
DOI: 10.1101/2020.03.12.989053
Abstract: Tissue growth in bioscaffolds is influenced significantly by pore geometry, but how this geometric dependence emerges from dynamic cellular processes such as cell proliferation and cell migration remains poorly understood. Here we investigate the influence of pore size on the time required to bridge pores in thin 3D-printed scaffolds. Experimentally, new tissue infills the pores continually from their perimeter under strong curvature control, which leads the tissue front to round off with time. Despite the varied shapes assumed by the tissue during this evolution, we find that time to bridge a pore simply increases linearly with the overall pore size. To disentangle the biological influence of cell behaviour and the mechanistic influence of geometry in this experimental observation, we propose a simple reaction–diffusion model of tissue growth based on Porous-Fisher invasion of cells into the pores. First, this model provides a good qualitative representation of the evolution of the tissue new tissue in the model grows at an effective rate that depends on the local curvature of the tissue substrate. Second, the model suggests that a linear dependence of bridging time with pore size arises due to geometric reasons alone, not to differences in cell behaviours across pores of different sizes. Our analysis suggests that tissue growth dynamics in these experimental constructs is dominated by mechanistic crowding effects that influence collective cell proliferation and migration processes, and that can be predicted by simple reaction–diffusion models of cells that have robust, consistent behaviours.
Publisher: Cold Spring Harbor Laboratory
Date: 24-09-2021
DOI: 10.1101/2021.09.24.461639
Abstract: The emerging field of soft robotics aims to emulate dynamic physiological locomotion. Soft robotics’ mimicry of naturally complex biomechanics makes them ideal platforms for exerting mechanical stimuli for patient-specific tissue maturation and disease modeling applications. Such platforms are essential for emulating highly flexible tissues such as the kneecap’s femoropopliteal artery (FPA), one of the most flexible arteries in the body, which flexes and bends during walking, standing, and crouching movements. The FPA is a frequent site of disease, where 80% of all peripheral artery diseases manifest, affecting over 200 million people worldwide. The complex biomechanical and hemodynamic forces within the FPA have been implicated in the frequent occurrence of PAD and lead to debilitating morbidities, such as limb-threatening ischemia. To better mimic these complex biomechanics, we developed an in-vitro bio-hybrid soft robot (BSR). First, Platsil OO-20 was identified as an ideal hyperelastomer for both cell culture and BSR fabrication using 3D printed molds. Then, employing a simulation-based design workflow, we integrated pneumatic network (PneuNet) actuators cast with Platsil OO-20, which extend in angular, longitudinal, and radial dimensions. Pressurizing the BSR PneuNets enabled a range of mechanical stimuli to be dynamically applied during tissue culture to mimic normal and diseased FPA flexions during daily walking and sitting poses, the most extreme being radial distensions of 20% and angular flexions of 140°. Finally, these designed, manufactured, and programmed vascular BSRs were seeded with mesenchymal stem cells and conditioned for 24 hours to highlight the effect of dynamic conditioning on cultured cell alignment, as well as type IV collagen production and the upregulation of smooth muscle phenotypes. Soft robotic bioreactor platforms that accurately mimic patient-, disease-, and lifestyle-specific mechanobiology will develop fundamental disease understanding, preoperative laboratory simulations for existing therapeutics, and biomanufacturing platforms for tissue-engineered implants.
Publisher: Institute of Electrical and Electronics Engineers (IEEE)
Date: 2022
Publisher: Elsevier BV
Date: 09-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA02633E
Abstract: A 3D biomimetic model for in vitro studies of pancreatic cancer.
Publisher: Cold Spring Harbor Laboratory
Date: 25-03-2021
DOI: 10.1101/2021.03.25.436898
Abstract: Tissue growth in three-dimensional (3D) printed scaffolds enables exploration and control of cell behaviour in biologically realistic geometries. Cell proliferation and migration in these experiments have yet to be explicitly characterised, limiting the ability of experimentalists to determine the effects of various experimental conditions, such as scaffold geometry, on cell behaviour. We consider tissue growth by osteoblastic cells in melt electro-written scaffolds that comprise thin square pores with sizes that we deliberately vary. We collect highly detailed temporal measurements of the average cell density, tissue coverage, and tissue geometry. To quantify tissue growth in terms of the underlying cell proliferation and migration processes, we introduce and calibrate a mechanistic mathematical model based on the Porous-Fisher reaction-diffusion equation. Parameter estimates and uncertainty quantification through profile likelihood analysis reveal consistency in the rate of cell proliferation and steady-state cell density between pore sizes. This analysis also serves as an important model verification tool: while the use of reaction-diffusion models in biology is widespread, the appropriateness of these models to describe tissue growth in 3D scaffolds has yet to be explored. We find that the Porous-Fisher model is able to capture features relating to the cell density and tissue coverage, but is not able to capture geometric features relating to the circularity of the tissue interface. Our analysis identifies two distinct stages of tissue growth, suggests several areas for model refinement, and provides guidance for future experimental work that explores tissue growth in 3D printed scaffolds. Advances in 3D printing technology have led to cell culture experiments that realistically capture natural biological environments. Despite the necessity of quantifying cell behaviour with parameters that can be compared between experiments, many existing mathematical models of tissue growth in these experiments neglect information relating to population size. We consider tissue growth by cells on 3D printed scaffolds that comprise square pores of various sizes in this work. We apply a relatively simple mathematical model based on the Porous-Fisher reaction-diffusion equation to interpret highly detailed measurements relating to both the cell density and the quantity of tissue deposited. We analyse the efficacy of such a model in capturing cell behaviour seen in the experiments and quantify cell behaviour in terms of parameters that carry a biologically meaningful interpretation. Our analysis identifies important areas for model refinement and provides guidance for future data-collection and experimentation that explores tissue growth in 3D printed scaffolds.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.BIOMATERIALS.2022.121514
Abstract: Industrial cell culture processes are inherently expensive, time-consuming, and variable. These limitations have become a critical bottleneck for the industrial translation of human cell and tissue biomanufacturing, as few human cell culture products deliver sufficient benefit, value, and consistency to offset their high manufacturing costs and produce useful clinical or biomedical solutions. Recent advances in biomedical image analysis and computational modelling can enhance the design and operation of high-efficiency tissue biomanufacturing platforms, as well as the high-content characterisation and monitoring of culture performance, to enable bioprocess control, optimisation, and automation. These computational technologies aim to maximize culture outcomes while minimizing variability and process development expense. In this review, we outline current resources and approaches which harness biomedical imaging and image-based computational models to design and operate efficient and robust human tissue biomanufacturing platforms.
Publisher: Informa UK Limited
Date: 02-08-2017
DOI: 10.1080/14786419.2016.1217201
Abstract: We have investigated the in vitro antibacterial bioactivity of dichloromethane-soluble fractions of Artemisia californica, Trichostema lanatum, Salvia apiana, Sambucus nigra ssp. cerulea and Quercus agrifolia Née against a ΔtolC mutant strain of Escherichia coli. These plants are traditional medicinal plants of the Chumash American Indians of Southern California. Bioassay-guided fractionation led to the isolation of three flavonoid compounds from A. californica: jaceosidin (1), jaceidin (2), and chrysoplenol B (3). Compounds 1 and 2 exhibited antibacterial activity against E. coli ΔtolC in liquid cultures. The in vitro activity of 1 against the enoyl reductase enzyme (FabI) was measured using a spectrophotometric assay and found to completely inhibit FabI activity at a concentration of 100 μM. However, comparison of minimum inhibitory concentration values for 1-3 against E. coli ΔtolC and an equivalent strain containing a plasmid constitutively expressing fabI did not reveal any selectivity for FabI in vivo.
Publisher: Cold Spring Harbor Laboratory
Date: 24-07-2020
DOI: 10.1101/2020.07.22.216812
Abstract: Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to create a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of IAs exist undiscovered until rupture. Current computer-aided UIA diagnoses sensitively detect and measure UIAs within cranial angiograms, but remain limited to low specificities whose output requires considerable neuroradiologist interpretation not amenable to broad screening efforts. To address these limitations, we propose an analysis which interprets single-voxel morphometry of segmented neurovasculature to identify UIAs. Once neurovascular anatomy of a specified resolution is segmented, interrelationships between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 minutes on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities. Rapid and automated detection of unruptured intracranial aneurysms (UIAs) in MRAs Highly specific, sensitive UIA detection to reduce radiologist input for screening Detection is versatile to image resolution, modality and has tuneable mm sensitivity
Publisher: Wiley
Date: 12-11-2020
DOI: 10.1111/JOPR.13274
Publisher: Elsevier
Date: 2020
Publisher: Cold Spring Harbor Laboratory
Date: 17-04-2023
DOI: 10.1101/2023.04.17.537257
Abstract: Vascular compliance is considered both a cause and a consequence of cardiovascular disease and a significant factor in the mid- and long-term patency of vascular grafts. However, the biomechanical effects of localised changes in compliance, such as during plaque development or after bypass grafting and stenting, cannot be satisfactorily studied with the available medical imaging technologies or surgical simulation materials. To address this unmet need, we developed a coupled silico-vitro platform which allows for the validation of numerical fluid-structure interaction (FSI) results as a numerical model and physical prototype. This numerical one-way and two-way FSI study is based on a three-dimensional computer model of an idealised femoral artery which is validated against patient measurements derived from the literature. The numerical results are then compared with experimental values collected from compliant arterial phantoms. Phantoms within a compliance range of 1.4 - 68.0%/100mmHg were fabricated via additive manufacturing and silicone casting, then mechanically characterised via ring tensile testing and optical analysis under direct pressurisation with differences in measured compliance ranging between 10 - 20% for the two methods. One-way FSI coupling underestimated arterial wall compliance by up to 14.71% compared to two-way FSI modelling. Overall, Smooth-On Solaris matched the compliance range of the numerical and in vivo patient models most closely out of the tested silicone materials. Our approach is promising for vascular applications where mechanical compliance is especially important, such as the study of diseases which commonly affect arterial wall stiffness, such as atherosclerosis, and the model-based design, surgical training, and optimisation of vascular prostheses.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Hindawi Limited
Date: 2018
DOI: 10.1155/2018/6230214
Abstract: Tissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion and cell-biomaterial attachment. Herein, we describe the fabrication and testing of ceramic hollow fibre membranes (HFs) able to separate red blood cells (RBCs) and mononuclear cells (MNCs) and be incorporated into 3D tissue models to improve nutrient and metabolite exchange. These HFs filtered RBCs from human umbilical cord blood (CB) suspensions of 20% RBCs to produce 90% RBC filtrate suspensions. When incorporated within 5 mL of 3D collagen-coated polyurethane porous scaffold, medium-perfused HFs maintained nontoxic glucose, lactate, pH levels, and higher cell densities over 21 days of culture in comparison to nonperfused 0.125 mL scaffolds. This hollow fibre bioreactor (HFBR) required a smaller per-cell medium requirement and operated at cell densities 10-fold higher than current 2D methods whilst allowing for continuous cell harvest through HFs. Herein, we propose HFs to improve 3D cell culture nutrient and metabolite diffusion, increase culture volume and cell density, and continuously harvest products for translational cell therapy biomanufacturing protocols.
Publisher: Mary Ann Liebert Inc
Date: 09-2015
Publisher: Figshare
Date: 2016
Publisher: Hindawi Limited
Date: 11-12-2019
DOI: 10.1002/TERM.2784
Abstract: Biomimetic materials are essential for the production of clinically relevant bone grafts for bone tissue engineering applications. Their ability to modulate stem cell proliferation and differentiation can be used to harness the regenerative potential of those cells and optimize the efficiency of engineered bone grafts. The arginyl-glycyl-aspartic acid (RGD) peptide has been recognized as the adhesion motif of various extracellular matrix proteins and can affect stem cell behaviour in biomaterials. Attempts to functionalize biomaterials with RGD have been limited to a maximum of 1- to 3-mm thickness scaffolds, overlooking the issue of core infiltration that represents a major hurdle in developing real thickness scaffolds. Herein, we present the cross-linking of RGD on the surface of "real thickness" (5 × 5 × 5 mm) porous polyurethane scaffolds (PU-RGD), to be used for the expansion and osteogenic differentiation of umbilical cord blood mesenchymal stem cells (UCB MSCs). RGD-functionalized scaffolds increased initial cell adhesion (1.5-fold to twofold) and achieved a 3.4-fold increase in cell numbers at the end of culture compared with a 1.5-fold increase in non-functionalized controls. Homogenous cell infiltration to the scaffold core was observed in the PU-RGD scaffolds. Importantly, PU-RGD scaffolds were able to enhance the osteogenic differentiation of UCB MSCs. Osteogenic gene and protein expression increased in scaffolds functionalized with 100 μg/ml RGD. Higher RGD concentrations (200 μg/ml) were less efficient in stimulating osteogenic differentiation. We conclude that robust RGD tethering to 3D PU "real thickness" scaffolds is possible and that it promotes core infiltration, expansion, and osteogenic differentiation of UCB MSCs for the purposes of bone regeneration.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Wiley
Date: 04-2019
Abstract: Additive manufacturing via melt electrowriting (MEW) can create ordered microfiber scaffolds relevant for bone tissue engineering however, there remain limitations in the adoption of new printing materials, especially in MEW of biomaterials. For ex le, while promising composite formulations of polycaprolactone with strontium-substituted bioactive glass have been processed into large or disordered fibres, from what is known, biologically-relevant concentrations (>10 wt%) have never been printed into ordered microfibers using MEW. In this study, rheological characterization is used in combination with a predictive mathematical model to optimize biomaterial formulations and MEW conditions required to extrude various PCL and PCL/SrBG biomaterials to create ordered scaffolds. Previously, MEW printing of PCL/SrBG composites with 33 wt% glass required unachievable extrusion pressures. The composite formulation is modified using an evaporable solvent to reduce viscosity 100-fold to fall within the predicted MEW pressure, temperature, and voltage tolerances, which enabled printing. This study reports the first fabrication of reproducible, ordered high-content bioactive glass microfiber scaffolds by applying predictive modeling.
Publisher: Elsevier BV
Date: 03-2019
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2020
End Date: 2021
Funder: Royal Brisbane and Women's Hospital Foundation
View Funded ActivityStart Date: 2018
End Date: 2019
Funder: Queensland University of Technology
View Funded ActivityStart Date: 2019
End Date: 2020
Funder: Institute for Health and Biomedical Innovation
View Funded ActivityStart Date: 03-2022
End Date: 03-2025
Amount: $447,654.00
Funder: Australian Research Council
View Funded Activity