ORCID Profile
0000-0002-1244-7673
Current Organisation
University of Sydney
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: MDPI AG
Date: 14-01-2022
DOI: 10.3390/BIOENGINEERING9010037
Abstract: Volumetric muscle loss (VML) is associated with irreversibly impaired muscle function due to traumatic injury. Experimental approaches to treat VML include the delivery of basic fibroblast growth factor (bFGF) or rehabilitative exercise. The objective of this study was to compare the effects of spatially nanopatterned collagen scaffold implants with either bFGF delivery or in conjunction with voluntary exercise. Aligned nanofibrillar collagen scaffold bundles were adsorbed with bFGF, and the bioactivity of bFGF-laden scaffolds was examined by skeletal myoblast or endothelial cell proliferation. The therapeutic efficacy of scaffold implants with either bFGF release or exercise was examined in a murine VML model. Our results show an initial burst release of bFGF from the scaffolds, followed by a slower release over 21 days. The released bFGF induced myoblast and endothelial cell proliferation in vitro. After 3 weeks of implantation in a mouse VML model, twitch force generation was significantly higher in mice treated with bFGF-laden scaffolds compared to bFGF-laden scaffolds with exercise. However, myofiber density was not significantly improved with bFGF scaffolds or voluntary exercise. In contrast, the scaffold implant with exercise induced more re-innervation than all other groups. These results highlight the differential effects of bFGF and exercise on muscle regeneration.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2019
DOI: 10.1038/S41598-019-53972-Y
Abstract: Current synthetic vascular grafts are not suitable for use in low-diameter applications. Silk fibroin is a promising natural graft material which may be an effective alternative. In this study, we compared two electrospun silk grafts with different manufacturing processes, using either water or hexafluoroisopropanol (HFIP) as solvent. This resulted in markedly different Young’s modulus, ultimate tensile strength and burst pressure, with HFIP spun grafts observed to have thicker fibres, and greater stiffness and strength relative to water spun. Assessment in a rat abdominal aorta grafting model showed significantly faster endothelialisation of the HFIP spun graft relative to water spun. Neointimal hyperplasia in the HFIP graft also stabilised significantly earlier, correlated with an earlier SMC phenotype switch from synthetic to contractile, increasing extracellular matrix protein density. An initial examination of the macrophage response showed that HFIP spun conduits promoted an anti-inflammatory M2 phenotype at early timepoints while reducing the pro-inflammatory M1 phenotype relative to water spun grafts. These observations demonstrate the important role of the manufacturing process and physical graft properties in determining the physiological response. Our study is the first to comprehensively study these differences for silk in a long-term rodent model.
Publisher: Wiley
Date: 07-05-2023
Abstract: Minimally invasive interventions using drug‐eluting stents or balloons are a first‐line treatment for certain occlusive cardiovascular diseases, but the major long‐term cause of failure is neointimal hyperplasia (NIH). The drugs eluted from these devices are non‐specific anti‐proliferative drugs, such as paclitaxel (PTX) or sirolimus (SMS), which do not address the underlying inflammation. MCC950 is a selective inhibitor of the NLRP3‐inflammasome, which drives sterile inflammation commonly observed in NIH. Additionally, in contrast to broad‐spectrum anti‐inflammatory drugs, MCC950 does not compromise global immune function due this selective activity. In this study, MCC950 is found to not impact the viability, integrity, or function of human coronary endothelial cells, in contrast to the non‐specific anti‐proliferative effects of PTX and SMS. Using an in vitro model of NLRP3‐mediated inflammation in murine macrophages, MCC950 reduced IL‐1 β expression, which is a key driver of NIH. In an in vivo mouse model of NIH in vascular grafts, MCC950 significantly enhanced re‐endothelialization and reduced NIH compared to PTX or SMS. These findings show the effectiveness of a targeted anti‐inflammatory drug‐elution strategy with significant implications for cardiovascular device intervention.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier
Date: 2018
Publisher: Elsevier BV
Date: 2023
Publisher: Frontiers Media SA
Date: 20-04-2021
DOI: 10.3389/FBIOE.2021.673212
Abstract: In recent years, the cost of drug discovery and development have been progressively increasing, but the number of drugs approved for treatment of cardiovascular diseases (CVDs) has been limited. Current in vitro models for drug development do not sufficiently ensure safety and efficacy, owing to their lack of physiological relevance. On the other hand, preclinical animal models are extremely costly and present problems of inaccuracy due to species differences. To address these limitations, tissue chips offer the opportunity to emulate physiological and pathological tissue processes in a biomimetic in vitro platform. Tissue chips enable in vitro modeling of CVDs to give mechanistic insights, and they can also be a powerful approach for drug screening applications. Here, we review recent advances in CVD modeling using tissue chips and their applications in drug screening.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.ACTBIO.2017.02.002
Abstract: Biomaterial scaffolds enhancing the engraftment of transplanted bone-marrow mononuclear cells (BM-MNC) have enormous potential for tissue regeneration applications. However, development of appropriate materials is challenging given the precise microenvironments required to support BM-MNC engraftment and function. In this study, we have developed a non-invasive, real-time tracking model of injected BM-MNC engraftment to wounds and implanted biomaterial scaffolds. BM-MNCs, encoded with firefly luciferase and enhanced GFP reporter genes, were tail vein injected into subcutaneously wounded mice. Luciferase-dependent cell bioluminescence curves revealed our injected BM-MNCs homed to and engrafted within subcutaneous wound sites over the course of 21days. Further immunohistochemical characterization showed that these engrafted cells drove functional changes by increasing the number of immune cells present at early time points and remodelling cell phenotypes at later time points. Using this model, we subcutaneously implanted electrospun polycaprolactone (PCL) and PCL/Collagen scaffolds, to determine differences in exogenous BM-MNC response to these materials. Following BM-MNC injection, immunohistochemical analysis revealed a high exogenous BM-MNC density around the periphery of PCL scaffolds consistent with a classical foreign body response. In contrast, transplanted BM-MNCs engrafted throughout PCL/Collagen scaffolds indicating an improved biological response. Importantly, these differences were closely correlated with the real-time bioluminescence curves, with PCL/Collagen scaffolds exhibiting a∼2-fold increase in maximum bioluminescence compared with PCL scaffolds. Collectively, these results demonstrate a new longitudinal cell tracking model that can non-invasively determine transplanted BM-MNC homing and engraftment to biomaterials, providing a valuable tool to inform the design scaffolds that help augment current BM-MNC tissue engineering strategies. Tracking the dynamic behaviour of transplanted bone-marrow mononuclear cells (BM-MNCs) is a long-standing research goal. Conventional methods involving contrast and tracer agents interfere with cellular function while also yielding false signals. The use of bioluminescence addresses these shortcomings while allowing for real-time non-invasive tracking in vivo. Given the failures of transplanted BM-MNCs to engraft into injured tissue, biomaterial scaffolds capable of attracting and enhancing BM-MNC engraftment at sites of injury are highly sought in numerous tissue engineering applications. To this end, the results from this study demonstrate a new longitudinal tracking model that can non-invasively determine exogenous BM-MNC homing and engraftment to biomaterials, providing a valuable tool to inform the design of scaffolds with implications for countless tissue engineering applications.
Publisher: American Chemical Society (ACS)
Date: 23-01-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3BM00448A
Abstract: Murine myoblasts cultured on combinatorial extracellular matrix (ECM) proteins are exposed to uniaxial strain. The combined effects of ECMs and strain on myogenesis are investigated by transcriptomic and protein analyses.
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.MSEC.2021.112057
Abstract: Annually increasing incidence of cardiac-related disorders and cardiac tissue's minimal regenerative capacity have motivated the researchers to explore effective therapeutic strategies. In the recent years, bioprinting technologies have witnessed a great wave of enthusiasm and have undergone steady advancements over a short period, opening the possibilities for recreating engineered functional cardiac tissue models for regenerative and diagnostic applications. With this perspective, the current review delineates recent developments in the sphere of engineered cardiac tissue fabrication, using traditional and advanced bioprinting strategies. The review also highlights different printing ink formulations, available cellular opportunities, and aspects of personalized medicines in the context of cardiac tissue engineering and bioprinting. On a concluding note, current challenges and prospects for further advancements are also discussed.
Publisher: American Chemical Society (ACS)
Date: 06-01-2020
Publisher: Public Library of Science (PLoS)
Date: 29-03-2017
Publisher: Future Medicine Ltd
Date: 05-2020
Abstract: Although stem cell therapy has tremendous therapeutic potential, clinical translation of stem cell therapy has yet to be fully realized. Recently, patient comorbidities and lifestyle choices have emerged to be important factors in the efficacy of stem cell therapy. Tobacco usage is an important risk factor for numerous diseases, and nicotine exposure specifically has become increasing more prevalent with the rising use of electronic cigarettes. This review describes the effects of nicotine exposure on the function of various stem cells. We place emphasis on the differential effects of nicotine exposure in vitro and as well as in preclinical models. Further research on the effects of nicotine on stem cells will deepen our understanding of how lifestyle choices can impact the outcome of stem cell therapies.
Publisher: Springer Science and Business Media LLC
Date: 30-07-2020
DOI: 10.1038/S41598-020-69591-X
Abstract: Multifunctional nanocarriers (MNCs) promise to improve therapeutic outcomes by combining multiple classes of molecules into a single nanostructure, enhancing active targeting of therapeutic agents and facilitating new combination therapies. However, nanocarrier platforms currently approved for clinical use can still only carry a single therapeutic agent. The complexity and escalating costs associated with the synthesis of more complex MNCs have been major technological roadblocks in the pathway for clinical translation. Here, we show that plasma polymerized nanoparticles (PPNs), synthesised in reactive gas discharges, can bind and effectively deliver multiple therapeutic cargo in a facile and cost-effective process compatible with up scaled commercial production. Delivery of siRNA against vascular endothelial growth factor (siVEGF) at extremely low concentrations (0.04 nM), significantly reduced VEGF expression in hard-to-transfect cells when compared with commercial platforms carrying higher siRNA doses (6.25 nM). PPNs carrying a combination of siVEGF and standard of care Paclitaxel (PPN-Dual) at reduced doses ( 100 µg/kg) synergistically modulated the microenvironment of orthotopic breast tumors in mice, and significantly reduced tumor growth. We propose PPNs as a new nanomaterial for delivery of therapeutics, which can be easily functionalised in any laboratory setting without the need for additional wet-chemistry and purification steps.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Wiley
Date: 17-10-2023
Publisher: Springer Science and Business Media LLC
Date: 21-03-2018
Publisher: American Chemical Society (ACS)
Date: 14-12-2020
Publisher: Mary Ann Liebert Inc
Date: 03-2016
Location: United States of America
No related grants have been discovered for Alex Ho Pang Chan.