ORCID Profile
0000-0001-9331-4698
Current Organisation
Queensland University of Technology - Translational Research Institute
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Biomaterials | Biomedical engineering | Manufacturing Engineering | Biomedical engineering not elsewhere classified | Biomaterials | Manufacturing Processes and Technologies (excl. Textiles) | Machine learning not elsewhere classified | Microtechnology | Petroleum and Reservoir Engineering | Timber, Pulp and Paper | Regenerative Medicine (incl. Stem Cells and Tissue Engineering) |
Oil and Gas Extraction | Wood, Wood Products and Paper not elsewhere classified | Scientific Instruments | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in Technology | Fabricated Metal Products not elsewhere classified
Publisher: Springer Science and Business Media LLC
Date: 25-04-2019
DOI: 10.1038/S41413-019-0049-8
Abstract: While stromal interactions are essential in cancer adaptation to hormonal therapies, the effects of bone stroma and androgen deprivation on cancer progression in bone are poorly understood. Here, we tissue-engineered and validated an in vitro microtissue model of osteoblastic bone metastases, and used it to study the effects of androgen deprivation in this microenvironment. The model was established by culturing primary human osteoprogenitor cells on melt electrowritten polymer scaffolds, leading to a mineralized osteoblast-derived microtissue containing, in a 3D setting, viable osteoblastic cells, osteocytic cells, and appropriate expression of osteoblast/osteocyte-derived mRNA and proteins, and mineral content. Direct co-culture of androgen receptor-dependent/independent cell lines (LNCaP, C4-2B, and PC3) led cancer cells to display functional and molecular features as observed in vivo. Co-cultured cancer cells showed increased affinity to the microtissues, as a function of their bone metastatic potential. Co-cultures led to alkaline phosphatase and collagen-I upregulation and sclerostin downregulation, consistent with the clinical marker profile of osteoblastic bone metastases. LNCaP showed a significant adaptive response under androgen deprivation in the microtissues, with the notable appearance of neuroendocrine transdifferentiation features and increased expression of related markers (dopa decarboxylase, enolase 2). Androgen deprivation affected the biology of the metastatic microenvironment with stronger upregulation of androgen receptor, alkaline phosphatase, and dopa decarboxylase, as seen in the transition towards resistance. The unique microtissues engineered here represent a substantial asset to determine the involvement of the human bone microenvironment in prostate cancer progression and response to a therapeutic context in this microenvironment.
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9769-5_2
Abstract: One of the major limitations of studying cancer in distant sites is the lack of representative laboratory models that mimic the biological processes occurring in vivo. In this protocol, we demonstrate the application of melt electrowriting technology (MEW) to provide 3D microfiber scaffolds suitable for this purpose. Using primary human cells, MEW scaffolds support the reproducible formation of human bone-like 3D microenvironments. Co-culture with human cancer cells provides an in vitro bioengineered model of metastases in bone, suitable for investigating cell-cell and cell-matrix interactions between bone and cancer cells. By proposing variations to standard tissue histology, immunohistochemistry, immunofluorescence, and 3D imaging techniques, we show how to characterize cell morphology and protein expression in a reproducibly engineered bone metastatic microtissue.
Publisher: Springer New York
Date: 2019
DOI: 10.1007/978-1-4939-9769-5_3
Abstract: The study of dynamic processes in the bone metastatic compartment has been challenged by the restrictive access and limited live imaging capabilities that in vivo bone models provide. In this protocol, we show the use of a human bone metastatic bioengineered microtissue for the quantitative investigation of cancer cells in an in vitro bone-like microenvironment. Using live cell epifluorescence microscopy, traditional- and spinning disc-confocal laser scanning microscopy, we demonstrate how to obtain multidimensional real-time data of fluorescently labeled cancer cells in the metastatic microenvironment. Using 4D imaging data processing software such as ImageJ and Imaris, we show how to transform qualitative images and videos into quantitative data of cancer cell attachment, morphology, proliferation, and migration in vitro in the human bone metastatic microtissue.
Publisher: American Vacuum Society
Date: 03-2015
DOI: 10.1116/1.4914380
Abstract: Direct writing melt electrospinning is an additive manufacturing technique capable of the layer-by-layer fabrication of highly ordered 3d tissue engineering scaffolds from micron-diameter fibers. The utility of these scaffolds, however, is limited by the maximum achievable height of controlled fiber deposition, beyond which the structure becomes increasingly disordered. A source of this disorder is charge build-up on the deposited polymer producing unwanted coulombic forces. In this study, the authors introduce a novel melt electrospinning platform with dual voltage power supplies to reduce undesirable charge effects and improve fiber deposition control. The authors produced and characterized several 90° cross-hatched fiber scaffolds using a range of needle/collector plate voltages. Fiber thickness was found to be sensitive only to overall potential and invariant to specific tip/collector voltage. The authors also produced ordered scaffolds up to 200 layers thick (fiber spacing 1 mm and diameter 40 μm) and characterized structure in terms of three distinct zones: ordered, semiordered, and disordered. Our in vitro analysis indicates successful cell attachment and distribution throughout the scaffolds, with little evidence of cell death after seven days. This study demonstrates the importance of electrostatic control for reducing destabilizing polymer charge effects and enabling the fabrication of morphologically suitable scaffolds for tissue engineering.
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/BJU.14474
Publisher: American Chemical Society (ACS)
Date: 03-12-2020
Publisher: Informa UK Limited
Date: 07-2019
DOI: 10.2147/IJN.S197737
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.BIOMATERIALS.2019.119402
Abstract: Representative in vitro models that mimic the native bone tumor microenvironment are warranted to support the development of more successful treatments for bone metastases. Here, we have developed a primary cell 3D model consisting of a human osteoblast-derived tissue-engineered construct (hOTEC) indirectly co-cultured with patient-derived prostate cancer xenografts (PDXs), in order to study molecular interactions in a patient-derived microenvironment context. The engineered biomimetic microenvironment had high mineralization and embedded osteocytes, and supported a high degree of cancer cell osteomimicry at the gene, protein and mineralization levels when co-cultured with prostate cancer PDXs from a lymph node metastasis (LuCaP35) and bone metastasis (BM18) from patients with primary prostate cancer. This fully patient-derived model is a promising tool for the assessment of new molecular mechanisms and as a personalized pre-clinical platform for therapy testing for patients with prostate cancer bone metastases.
Publisher: MDPI AG
Date: 24-02-2020
Abstract: Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-based drug delivery system (GelMA-DDS) for the sustained local delivery of paclitaxel-based Abraxane®, for the prevention of local breast cancer recurrence following mastectomy. GelMA-DDS readily encapsulated Abraxane® with a maximum of 96% encapsulation efficiency. The mechanical properties of the hydrogel system were not affected by drug loading. Tuning of the physical properties, by varying GelMA concentration, allowed tailoring of GelMA-DDS mesh size, where decreasing the GelMA concentration provided overall more sustained cumulative release (significant differences between 5%, 10%, and 15%) with a maximum of 75% over three months of release, identified to be released by diffusion. Additionally, enzymatic degradation, which more readily mimics the in vivo situation, followed a near zero-order rate, with a total release of the cargo at various rates (2–14 h) depending on GelMA concentration. Finally, the results demonstrated that Abraxane® delivery from the hydrogel system led to a dose-dependent reduction of viability, metabolic activity, and live-cell density of triple-negative breast cancer cells in vitro. The GelMA-DDS provides a novel and simple approach for the sustained local administration of anti-cancer drugs for breast cancer recurrence.
Publisher: Wiley
Date: 28-11-2019
Publisher: American Association for the Advancement of Science (AAAS)
Date: 02-07-2021
Abstract: In vitro engineering of a bone metastases model allows us to study the effects of antiandrogens in advanced prostate cancer.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Mary Ann Liebert Inc
Date: 02-2016
Publisher: American Scientific Publishers
Date: 12-2014
Publisher: Springer International Publishing
Date: 2015
Publisher: Wiley
Date: 12-04-2012
DOI: 10.1002/JBM.A.34167
Abstract: The use of magnetism in tissue engineering is a very promising approach, in fact magnetic scaffolds are able not only to support tissue regeneration, but they can be activated and work like a magnet attracting functionalized magnetic nanoparticles (MNPs) injected close to the scaffold enhancing tissue regeneration. This study aimed to assess the in vivo biocompatibility and osteointegrative properties of novel magnetic scaffolds. Two hydroxyapatite/collagen (70/30 wt %) magnetic scaffolds were magnetized with two different techniques: direct nucleation of biomimetic phase and superparamagnetic nanoparticles (MNPs) on self-assembling collagen fibers (MAG-A) and scaffold impregnation in ferro-fluid solution (MAG-B). Magnetic scaffolds were implanted in rabbit distal femoral epiphysis and tibial mid-diaphysis. Histopathological screening showed no inflammatory reaction due to MNPs. Significantly higher bone healing rate (ΔBHR) results were observed in MAG-A in comparison to MAG-B. Significant differences were also found between experimental times with an increase in ΔBHR from 2 to 4 weeks for both scaffolds in trabecular bone, while only for MAG-B (23%, p < 0.05) in cortical bone. The proposed magnetic scaffolds seem to be promising for magnetic guiding in orthopedic tissue engineering applications and they will be suitable to treat also several pathologies in regenerative medicine area.
Publisher: MyJove Corporation
Date: 31-03-2022
DOI: 10.3791/61261
Abstract: Current mixing steps of viscous materials rely on repetitive and time-consuming tasks which are performed mainly manually in a low throughput mode. These issues represent drawbacks in workflows that can ultimately result in irreproducibility of research findings. Manual-based workflows are further limiting the advancement and widespread adoption of viscous materials, such as hydrogels used for biomedical applications. These challenges can be overcome by using automated workflows with standardized mixing processes to increase reproducibility. In this study, we present step-by-step instructions to use an open source protocol designer, to operate an open source workstation, and to identify reproducible mixtures. Specifically, the open source protocol designer guides the user through the experimental parameter selection and generates a ready-to-use protocol code to operate the workstation. This workstation is optimized for pipetting of viscous materials to enable automated and highly reliable handling by the integration of temperature docks for thermoresponsive materials, positive displacement pipettes for viscous materials, and an optional tip touch dock to remove excess material from the pipette tip. The validation and verification of mixtures are performed by a fast and inexpensive absorbance measurement of Orange G. This protocol presents results to obtain 80% (v/v) glycerol mixtures, a dilution series for gelatin methacryloyl (GelMA), and double network hydrogels of 5% (w/v) GelMA and 2% (w/v) alginate. A troubleshooting guide is included to support users with protocol adoption. The described workflow can be broadly applied to a number of viscous materials to generate user-defined concentrations in an automated fashion.
Publisher: MDPI AG
Date: 19-05-2021
DOI: 10.3390/BIOMEDICINES9050574
Abstract: Water plays a primary role in the functionality of biomedical polymers such as hydrogels. The state of water, defined as bound, intermediate, or free, and its molecular organization within hydrogels is an important factor governing biocompatibility and hemocompatibility. Here, we present a systematic study of water states in gelatin methacryloyl (GelMA) hydrogels designed for drug delivery and tissue engineering applications. We demonstrate that increasing ionic strength of the swelling media correlated with the proportion of non-freezable bound water. We attribute this to the capability of ions to create ion–dipole bonds with both the polymer and water, thereby reinforcing the first layer of polymer hydration. Both pH and ionic strength impacted the mesh size, having potential implications for drug delivery applications. The mechanical properties of GelMA hydrogels were largely unaffected by variations in ionic strength or pH. Loading of cefazolin, a small polar antibiotic molecule, led to a dose-dependent increase of non-freezable bound water, attributed to the drug’s capacity to form hydrogen bonds with water, which helped recruit water molecules in the hydrogels’ first hydration layer. This work enables a deeper understanding of water states and molecular arrangement at the hydrogel–polymer interface and how environmental cues influence them.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.ACTBIO.2009.09.017
Abstract: In recent years, interest in tissue engineering and its solutions has increased considerably. In particular, scaffolds have become fundamental tools in bone graft substitution and are used in combination with a variety of bio-agents. However, a long-standing problem in the use of these conventional scaffolds lies in the impossibility of re-loading the scaffold with the bio-agents after implantation. This work introduces the magnetic scaffold as a conceptually new solution. The magnetic scaffold is able, via magnetic driving, to attract and take up in vivo growth factors, stem cells or other bio-agents bound to magnetic particles. The authors succeeded in developing a simple and inexpensive technique able to transform standard commercial scaffolds made of hydroxyapatite and collagen in magnetic scaffolds. This innovative process involves dip-coating of the scaffolds in aqueous ferrofluids containing iron oxide nanoparticles coated with various biopolymers. After dip-coating, the nanoparticles are integrated into the structure of the scaffolds, providing the latter with magnetization values as high as 15 emu g(-)(1) at 10 kOe. These values are suitable for generating magnetic gradients, enabling magnetic guiding in the vicinity and inside the scaffold. The magnetic scaffolds do not suffer from any structural damage during the process, maintaining their specific porosity and shape. Moreover, they do not release magnetic particles under a constant flow of simulated body fluids over a period of 8 days. Finally, preliminary studies indicate the ability of the magnetic scaffolds to support adhesion and proliferation of human bone marrow stem cells in vitro. Hence, this new type of scaffold is a valuable candidate for tissue engineering applications, featuring a novel magnetic guiding option.
Publisher: Mary Ann Liebert Inc
Date: 10-2021
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/174942
Abstract: There remains a substantial shortfall in the treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue-engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors, which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However due to the cost and potential complications associated with growth factors, controlling the rate of release is an important design consideration when developing new bone tissue engineering strategies. This paper will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.
Publisher: Wiley
Date: 21-02-2023
Abstract: Increasing evidence shows bone marrow (BM)‐adipocytes as a potentially important contributor in prostate cancer (PCa) bone metastases. However, a lack of relevant models has prevented the full understanding of the effects of human BM‐adipocytes in this microenvironment. It is hypothesized that the combination of tunable gelatin methacrylamide (GelMA)‐based hydrogels with the biomimetic culture of human cells would offer a versatile 3D platform to engineer human bone tumor microenvironments containing BM‐adipocytes. Human osteoprogenitors, adipocytes, and PCa cells are in idually cultured in vitro in GelMA hydrogels, leading to mineralized, adipose, and PCa tumor 3D microtissues, respectively. Osteoblast mineralization and tumor spheroid formation are tailored by hydrogel stiffness with lower stiffnesses correlating with increased mineralization and tumor spheroid size. Upon coculture with tumor cells, BM‐adipocytes undergo morphological changes and delipidation, suggesting reciprocal interactions between the cell types. When brought in vivo, the mineralized and adipose microtissues successfully form a humanized fatty bone microenvironment, presenting, for the first time, with human adipocytes. Using this model, an increase in tumor burden is observed when human adipocytes are present, suggesting that adipocytes support early bone tumor growth. The advanced platform presented here combines natural aspects of the microenvironment with tunable properties useful for bone tumor research.
Publisher: Frontiers Media SA
Date: 31-03-2021
DOI: 10.3389/FBIOE.2021.638577
Abstract: Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa , two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.
Publisher: American Chemical Society (ACS)
Date: 04-06-2021
DOI: 10.1021/JACS.1C03950
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.EJPB.2014.03.008
Abstract: The fabrication of tailored microparticles for delivery of therapeutics is a challenge relying upon a complex interplay between processing parameters and materials properties. The emerging use of electrospraying allows better tailoring of particle morphologies and sizes than current techniques, critical to reproducible release profiles. While dry encapsulation of proteins is essential for the release of active therapeutics from microparticles, it is currently uncharacterized in electrospraying. To this end, poly(ethylene glycol) (PEG) was assessed as a micronizing and solubilizing agent for dry protein encapsulation and release from electrosprayed particles made from polycaprolactone (PCL). The physical effect of PEG in protein-loaded poly(lactic-co-glycolic acid) (PLGA) particles was also studied, for comparison. The addition of 5-15 wt% PEG 6 kDa or 35 kDa resulted in reduced PCL particle sizes and broadened distributions, which could be improved by tailoring the electrospraying processing parameters, namely by reducing polymer concentration and increasing flow rate. Upon micronization, protein particle size was reduced to the micrometer domain, resulting in homogenous encapsulation in electrosprayed PCL microparticles. Microparticle size distributions were shown to be the most determinant factor for protein release by diffusion and allowed specific control of release patterns.
Publisher: Wiley
Date: 16-09-2014
Abstract: A novel strategy is reported to produce biodegradable microfiber-scaffolds layered with high densities of microparticles encapsulating a model protein. Direct electrospraying on highly porous melt electrospun scaffolds provides a reproducible scaffold coating throughout the entire architecture. The burst release of protein is significantly reduced due to the immobilization of microparticles on the surface of the scaffold and release mechanisms are dependent on protein-polymer interactions. The composite scaffolds have a positive biological effect in contact with precursor osteoblast cells up to 18 days in culture. The scaffold design achieved with the techniques presented here endorses these new composite scaffolds as promising templates for growth factor delivery.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 11-2012
Publisher: MDPI AG
Date: 16-11-2021
Abstract: The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% w/v polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3–13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against S. aureus, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.
Publisher: MDPI AG
Date: 05-01-2011
DOI: 10.3390/POLYM3010131
Publisher: Elsevier BV
Date: 11-2019
Publisher: Frontiers Media SA
Date: 12-09-2019
Publisher: Springer Science and Business Media LLC
Date: 11-09-2020
DOI: 10.1038/S41598-020-71900-3
Abstract: Polydopamine (PDA) has been recently used as a versatile priming layer for further functionalization of a biomaterial surface, particularly in biomimetic mineralization of biomaterials. Yet most of the existing literature is on inorganic substrates and the underlying effects of the PDA layer coatings on the nucleation and mineralization process and the mineral-substrate interface have not been clearly identified. Here we aimed to investigate the effects of the PDA layer on the nucleation and growth and interfacial morphology of calcium phosphate mineral layer (CaP) from 10× simulated body fluid (10× SBF) on polymeric substrates. It is found that the nucleation of CaP on PDA-coated surface favors a mixed “islanding” and planar growth mode (Stranski–Krastanov) while the “islanding” mode (Volmer–Weber) was observed on the surface without PDA. This different early nucleation stage of mineralization was found to correlate with a more “bonded” interface between the mineral layer and the PDA-coated substrates, a slight increase in the interfacial strength and a different delamination mode. This study therefore provided new insights on how polydopamine priming layer influenced the mineralization process and the interface between the mineral layer and the substrate.
Publisher: Wiley
Date: 10-08-2017
Location: Australia
Location: Italy
Start Date: 2016
End Date: 2018
Funder: Prostate Cancer Foundation of Australia
View Funded ActivityStart Date: 2015
End Date: 2020
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: Advance Queensland
View Funded ActivityStart Date: 06-2020
End Date: 12-2023
Amount: $390,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2023
End Date: 12-2025
Amount: $449,148.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2024
End Date: 12-2026
Amount: $450,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2019
End Date: 06-2025
Amount: $3,981,223.00
Funder: Australian Research Council
View Funded Activity