Dr. Joshua Chou is a lecturer in the School of Life Sciences and the Course Director for the MSc in Biomedical Engineering. Dr. Chou also serve as a core member of the Centre of Health Technology and is a member of the UTS Postdoctoral Association.
Dr. Chou’s laboratory works at the interface of biomaterials, cell mechanics, physics and cell biology, seeking to understand how physical properties and biological function affect each other in different cellular systems and diseases. These basic mechanical processes have profound effect in health (organ growth, heart/lung development) and diseases including cancer and osteoporosis.
Working with an international multidisciplinary team of engineers, biologists, and physicists from Harvard and MIT, the team seeks to understand physical properties of the living cell and their impact in health and disease.
By combining and applying the latest technology in mechanobiology, CRISPR/cas9 gene editing with single-cell sequencing, AI machine learning with super-resolution imaging, microfluidics and micro-contact patterning, Dr. Chou seek to understand disease mechanotransduction in hope of identifying therapeutic targets.
Dean’s Scholar, Harvard School of Dental Medicine: Mechanobiology, microfluidics and CRISPR/cas9 gene editing.
Japan Society for the Promotion of Science Postdoctoral Fellow: Development of pharmaceutical drug delivery systems and in-vivo rodent experiments and imaging.
UTS Chancellor Postdoctoral Fellow: Development of biomimetic bone scaffold for bone tissue regeneration
Dr. Chou is an Editor for the Journal of Australia Ceramic Society and the Journal of Advances in Ceramic Science and Engineering. He also serves as a member of the editorial board for Journal of Tissue Engineering and Regenerative Medicine and International Journal of Biomaterials.
Dr. Chou’s research has had publicity in the national media: radio (ABC, 2ser), newspaper (Sydney Morning Herald (2010) and magazines (Materials Australia, U:Magazine, Researcher in Focus).
- Dean's Scholar at Harvard School of Dental Medicine (2016)
- Japan Society for the Promotion of Science Postdoctoral Research Fellowship (2012)
- The Australia Endeavour Cheung Kong Research Fellowship Award (2011)
- University of Technology Sydney Chancellor Postdoctoral Research Fellowship (2011)
Prizes, Awards, Honours
- Rebecca L Cooper Medical Foundation Medical Research Grant (2016)
- International Team for Implantology (ITI) Advanced Research Grant (2015)
- Rebecca L Cooper Medical Foundation Medical Research Grant (2015)
- Bioceramic 25 – Best Oral Presentation Award (2013)
- Asian Bioceramic Symposium Best Presentation Award (2011)
- Australia 3-Minute Thesis Competition Top 5 Australia (2010)
- Bioceramic 19. Best Oral Presentation Award (2007)
- UTS Centre for Health Technologies Core, member (2011 – 2015)
- UTS Science Faculty Board, member (2009 – 2015)
- UTS Student Misconduct Appeals Committee, member (2009 – 2011)
- American Society for Bone and Mineral Research, member (2014 – Present)
- Australia Ceramic Society, member (2009 – Present)
- Australasian Society for Biomaterial & Tissue Engineering, member (2009 – Present)
- Tissue Engineering & Regenerative Medicine Society, member (2010 – Present)
- Japan Society for Bone Mineral Research, member (2013 – Present)
Can supervise: YES
- Mechanobiology & Cell Mechanics
- Cancer Physics
- Gene Editing and Genetic Engineering/ Bioinformatics
- Controlled Stem Cell Differentiation
- Bone Mechanics and Diseases
- AI Machine Learning for Super-Resolution Bioimaging
- Lab and Organ on Chip
- Neurodegenerative Diseases
- Single-Cell RNA-Seq
Dr. Chou has experience in mentoring Honors, PhD and Postdoctoral Fellows. He was the course director for the Advanced Graduate Education research program at Harvard. Dr. Chou is highly interested in teaching students and mentoring early career researchers.
Please contact Dr. Chou directly to discuss potential projects.
Project offerings are available in the following areas but not limited to.
>Bone cell biology
>AI Machine Learning and Deep Learning
>Development of Biomedical Microfluidic Devices
Aydogdu, MO, Chou, J, Altun, E, Ekren, N, Cakmak, S, Eroglu, M, Osman, AA, Kutlu, O, Oner, ET, Avsar, G, Oktar, FN, Yilmaz, I & Gunduz, O 2019, 'Production of the biomimetic small diameter blood vessels for cardiovascular tissue engineering', International Journal of Polymeric Materials and Polymeric Biomaterials, pp. 1-13.View/Download from: Publisher's site
© 2018 Taylor & Francis A novel biomimetic vascular graft scaffolds were produced by electrospinning method with the most superior characteristics to be a proper biomimetic small diameter blood vessel using Polycaprolactone(PCL), Ethyl Cellulose(EC) and Collagen Type-1 were used to create the most convenient synergy of a natural and synthetic polymer to achieve similarity to native small diameter blood vessels. Scanning Electron Microscopy(SEM), Fourier Transform Infrared Spectroscopy(FTIR), Differential Scanning Calorimetry Analysis(DSC), tensile measurement tests, and in-vitro and in-vivo applications were performed. Results indicated significant properties such as having 39.33nm minimum, 104.98nm average fiber diameter, 3.2MPa young modulus and 135% relative cell viability.
Hao, J, Chou, J, Kuroda, S, Otsuka, M, Kasugai, S & Lang, NP 2018, 'Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat.', Clinical Oral Implants Research, vol. 29, no. 2, pp. 227-234.View/Download from: UTS OPUS or Publisher's site
To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel-forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model.The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum-derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200-l single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks.The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM-0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05).When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive mann...
Lu, R, Wang, C, Wang, X, Wang, Y, Wang, N, Chou, J, Li, T, Zhang, Z, Ling, Y & Chen, S 2018, 'Effects of hydrogenated TiO2 nanotube arrays on protein adsorption and compatibility with osteoblast-like cells.', International Journal of Nanomedicine, vol. 13, pp. 2037-2049.View/Download from: UTS OPUS or Publisher's site
Modified titanium (Ti) substrates with titanium dioxide (TiO2) nanotubes have broad usage as implant surface treatments and as drug delivery systems.To improve drug-loading capacity and accelerate bone integration with titanium, in this study, we hydrogenated anodized titanium dioxide nanotubes (TNTs) by a thermal treatment. Three groups were examined, namely: hydrogenated TNTs (H2-TNTs, test), unmodified TNTs (air-TNTs, control), and Ti substrates (Ti, control).Our results showed that oxygen vacancies were present in all the nanotubes. The quantity of -OH groups greatly increased after hydrogenation. Furthermore, the protein adsorption and loading capacity of the H2-TNTs were considerably enhanced as compared with the properties of the air-TNTs (P<0.05). Additionally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to investigate the interactions of TNTs with proteins. During the protein-loading process, the H2-TNTs not only enabled rapid protein adsorption, but also decreased the rate of protein elution compared with that of the air-TNTs. We found that the H2-TNTs exhibited better biocompatibility than the air-TNT and Ti groups. Both cell adhesion activity and alkaline phosphatase activity were significantly improved toward MG-63 human osteoblast-like cells as compared with the control groups (P<0.05).We conclude that hydrogenated TNTs could greatly improve the loading capacity of bioactive molecules and MG-63 cell proliferation.
Wang, Y, Cui, W, Chou, J, Wen, S, Sun, Y & Zhang, H 2018, 'Electrospun nanosilicates-based organic/inorganic nanofibers for potential bone tissue engineering.', Colloids and surfaces. B, Biointerfaces, vol. 172, pp. 90-97.View/Download from: UTS OPUS or Publisher's site
Although growth factors and drugs (BMP-2, dexamethasone, etc.) have been widely used for bone tissue engineering, they have unignored limits such as adverse effects at high concentrations and easy inactivation in vivo. Accordingly, more osteoinductive supplements without side effects should be considered as alternatives in the design of bone tissue engineering scaffolds. Nanosilicate is a bioactive inorganic nanomaterial consisting of hydrous sodium lithium magnesium silicate, which is recently found to be safe and effective for bone induction. In this study, a range of organic/inorganic nanofibrous scaffolds with varied nanosilicate concentrations (0%, 1%, 5%, and 10% w/w to PCL matrix) were successfully fabricated via electrospinning. The tensile properties of the nanofibers were enhanced at low nanosilicate concentrations, and the incorporation of nanosilicates had no influence on cytocompatibility. Besides, in vitro osteogenesis experiments showed that nanosilicates-doped nanofibers were capable of inducing bone formation better than pure PCL nanofiber samples. More importantly, the results of histological and immunohistochemical assessments further revealed that the nanosilicates-enriched nanofibers had a significant potential of ectopic bone formation in vivo, while the pure PCL samples only induced limited osteogenic cues. All these results indicate that the nanosilicates-based organic/inorganic nanofibers may be potentially efficient for bone tissue engineering.
Kim, H, Wrann, CD, Jedrychowski, M, Vidoni, S, Kitase, Y, Nagano, K, Zhou, C, Chou, J, Parkman, V-JA, Novick, SJ, Strutzenberg, TS, Pascal, BD, Le, PT, Brooks, DJ, Roche, AM, Gerber, KK, Mattheis, L, Chen, W, Tu, H, Bouxsein, ML, Griffin, PR, Baron, R, Rosen, CJ, Bonewald, LF & Spiegelman, BM 2018, 'Irisin Mediates Effects on Bone and Fat via V Integrin Receptors.', Cell, vol. 175, no. 7, pp. 1756-1768.e17.View/Download from: UTS OPUS or Publisher's site
Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the V class of integrins, and biophysical studies identify interacting surfaces between irisin and V/5 integrin. Chemical inhibition of the V integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.
Sun, Y, Zhang, W, Wang, B, Xu, X, Chou, J, Shimoni, O, Ung, AT & Jin, D 2018, 'A supramolecular self-assembly strategy for upconversion nanoparticle bioconjugation.', Chemical communications (Cambridge, England), vol. 54, no. 31, pp. 3851-3854.View/Download from: UTS OPUS or Publisher's site
An efficient surface modification for upconversion nanoparticles (UCNPs) is reported via supramolecular host-guest self-assembly. Cucurbituril (CB) can provide a hydrophilic surface and cavities for most biomolecules. High biological efficiency, activity and versatility of the approach enable UCNPs to be significantly applied in bio-imaging, early disease detection, and bio-sensing.
Nguyen Vo, TN, Hao, J, Chou, J, Oshima, M, Aoki, K, Kuroda, S, Kaboosaya, B & Kasugai, S 2017, 'Ligature induced peri-implantitis: tissue destruction and inflammatory progression in a murine model.', Clinical Oral Implants Research, vol. 28, no. 2, pp. 129-136.View/Download from: UTS OPUS or Publisher's site
The aim of this study was to investigate tissue destruction and inflammatory progression of ligature-induced peri-implantitis in mice and to establish an alternative murine model of peri-implantitis.Sixty male C57BL/6NCrSlc mice (4-week-old) were used and the maxillary right first molars were extracted. Eight weeks after extraction, custom-made pure titanium machined screw type implants (0.8 × 1.5 mm) were placed, one implant per animal. Four weeks later, 5-0 silk ligatures were applied around implant necks to induce peri-implantitis. Animals were sacrificed at 0 (before ligature), 7, 14, 21 and 28 days after ligature. Half of the samples were analyzed radiologically and histologically to measure bone level change, osteoclast number, density, and distribution. The rest of the samples was used to determine the relative mRNA expression levels of IL-1 and TNF- with RT-PCR analysis.Bone levels at all sites (buccal, palatal, mesial, distal) decreased 40-50% significantly 28 days after ligature (P < 0.01). Osteoclast number at all post-ligature time points increased significantly (P < 0.05). However, their density at day 28 decreased significantly compared to that of day 21 (P < 0.05). Accordingly, IL-1 and TNF- mRNA expression increased significantly at the early time points but decreased significantly at day 28 after ligature (P < 0.05).Inflammatory response followed by significant peri-implant bone resorption suggested 28 days ligation is sufficient to successfully induce peri-implantitis in the current mice model. This model might open a new avenue to study the pathogenesis and mechanism of peri-implantitis.
Andronescu, E, Brown, JM, Oktar, FN, Agathopoulos, S, Chou, J & Obata, A 2016, 'Nanomaterials for Medical Applications: Benefits and Risks', JOURNAL OF NANOMATERIALS.View/Download from: UTS OPUS or Publisher's site
Ekren, N, Gunduz, O, Celik, S, Ayata, B, Sahin, YM, Chou, J, Ben-Nissan, B, Salman, S, Gokce, H & Oktar, FN 2016, 'Production of apatite from snail shells for biomedical engineering applications', Key Engineering Materials, vol. 696, pp. 51-56.View/Download from: UTS OPUS or Publisher's site
© 2016 Trans Tech Publications, Switzerland. Bioceramics is very important application for dental and orthopedic procedures. Beside all these normal procedures traffic accidents are requiring increasing number of graft, prostheses and orthosis applications. Bioceramics can be produced from local and natural sources with various methods. Those can be produced from various bone structures through calcination (at high temperatures) or with diluted hydrochloric acid (HCl) application & freeze drying. Beside these methods calcite and aragonite structures like from sea shells and egg shells bioceramic production can be realized through mechanochemical processing via a simple hot-plate or ultrasonic equipment. A fresh water snail shell (Zebra Nerite Snail-Neritina natalensis) was prepared as bioceramic production source. The resulting hydroxyapatite (HA) powders were obtained without any impurities. At two varying temperature of 865 and 885 0C the snail shells was transformed to HA bioceramics. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential thermal analysis (TG/DTA) were evaluated.
Inan, AT, Gunduz, O, Sahin, YM, Ekren, N, Salman, S, Chou, J, Ben-Nissan, B, Gokce, H & Oktar, FN 2016, 'Novel Bioceramic production via mechanochemical conversion from plate limpet (Tectura scutum)-Shells', Key Engineering Materials, vol. 696, pp. 45-50.View/Download from: UTS OPUS or Publisher's site
© 2016 Trans Tech Publications, Switzerland. Calcium phosphates are very important biomaterials for orthopaedic and dental applications. Hydroxyapatite (HA) is one of the important phases used for grafting. Those are produced from synthetic and natural sources with various methods. Especially nano-bioceramics can be produced through calcitic and aragonitic structures (i.e. mussel shells, sea snail shells, land snail shells and sea urchin shells). The plate limpet shells were used. The plate limpet is a gastropod, a soft-bodied invertebrate (an animal without a backbone) that is protected by a very hard, flattened conical shell. In this study the Plate Limpet (Tectura scutum) shells were obtained from a local gift store in Istanbul. The habitation of these limpets broadens from south Alaska down to California-Mexico. First the exact 97 % CaCO3 content was measured with thermal analysis (DTA/TGA). Here in this study agitation was preformed on a hot-plate. First the temperature was fixed at 80 °C for 15 min. Then equivalent amount to 1.92 mmol CaO H3PO4was added dropwise for affecting HA phase formation and the reaction was set on a hotplate for 8 hours. The dried sediments HA part was divided into 2 groups. One group was sintered to 835 °C and second group to 855 °C. Here x-ray diffraction and scanning electron microscope (SEM) analyses were performed. From the study various HA phases and TCP phases were obtained. A previous study done with Atlantic Deer Cowrie encourages nanobioceramic production from natural sources. This study proposes that mechanochemical agitation with very simple way for producing nano-sized calcium phosphates for future bioengineering scaffold applications.
Chou, J, Ito, T, Otsuka, M, Ben-Nissan, B & Milthorpe, B 2016, 'The effectiveness of the controlled release of simvastatin from -TCP macrosphere in the treatment of OVX mice.', Journal of tissue engineering and regenerative medicine, vol. 10, no. 3, pp. E195-E203.View/Download from: Publisher's site
Simvastatin, a cholesterol treatment drug, has been shown to stimulate bone regeneration. As such, there has been an increase interest in the development of suitable materials and systems for the delivery of simvastatin. Without the appropriate dosage of simvastatin, the therapeutic effects on bone growth will be significantly reduced. Furthermore, similar to many pharmaceutical compounds, at high concentration simvastatin can cause various adverse side-effects. Given the associated side-effects with the usage of simvastatin, the development of suitable controlled drug release system is pertinent. Calcium phosphate in particularly beta-tricalcium phosphate (-TCP) has been extensively studied and used as a carrier material for drug delivery system. In this study, Foraminifera exoskeletons were used as calcium carbonate precursor materials, which were hydrothermally converted to -TCP as a carrier material for simvastatin. Natural marine exoskeletons posses interconnected and uniformly porous network capable of improving drug loading and release rate. To prolong the release of simvastatin, an apatite coating was made around the -TCP sample and in vitro release studies in simulated body fluid (SBF) showed a significant decrease in release rate. Osteoporotic mice were used to examine the compare therapeutic effectiveness of -TCP, -TCP with simvastatin, apatite-coated -TCP with simvastatin and direct injection of simvastatin near the right femur of the mice. Localized and systemic effect were compared with the femur of the non-implanted side (left) and showed that -TCP with or without simvastatin was able to induce significant bone formation over 6weeks. Mechanical analysis showed that apatite-coated -TCP with simvastatin produced significantly stronger bones compared with other experimental groups. This study shows that natural exoskeletons with the appropriate structure can be successfully used as a drug delivery system for simvastatin and can its release ca...
Chou, J, Komuro, M, Hao, J, Kuroda, S, Hattori, Y, Ben-Nissan, B, Milthorpe, B & Otsuka, M 2016, 'Bioresorbable zinc hydroxyapatite guided bone regeneration membrane for bone regeneration', Clinical Oral Implants Research, vol. 27, no. 3, pp. 354-360.View/Download from: UTS OPUS or Publisher's site
Hattori, Y, Mori, H, Chou, J & Otsuka, M 2016, 'Mechanochemical synthesis of zinc-apatitic calcium phosphate and the controlled zinc release for bone tissue engineering', DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, vol. 42, no. 4, pp. 595-601.View/Download from: UTS OPUS or Publisher's site
Hao, J, Acharya, A, Chen, K, Chou, J, Kasugai, S & Lang, NP 2015, 'Novel bioresorbable strontium hydroxyapatite membrane for guided bone regeneration', CLINICAL ORAL IMPLANTS RESEARCH, vol. 26, no. 1, pp. 1-7.View/Download from: Publisher's site
Hao, J, Chou, J, Kuroda, S, Otsuka, M, Kasugai, S & Lang, NP 2015, 'Strontium hydroxyapatite in situ gel-forming system - a new approach forminimally invasive bone augmentation', CLINICAL ORAL IMPLANTS RESEARCH, vol. 26, no. 5, pp. 581-585.View/Download from: UTS OPUS or Publisher's site
Wang, X, Zakaria, O, Madi, M, Hao, J, Chou, J & Kasugai, S 2015, 'Vertical bone augmentation induced by ultrathin hydroxyapatite sputtered coated mini titanium implants in a rabbit calvaria model.', Journal of biomedical materials research. Part B, Applied biomaterials, vol. 103, no. 8, pp. 1700-1708.View/Download from: UTS OPUS or Publisher's site
BACKGROUND: The purpose of this study was to evaluate the vertical new bone formation induced by sputtered HA-coated titanium implants (HA-coated) compared with sandblasted acid-etched titanium implants (noncoated) in a rabbit calvarial model. MATERIALS AND METHOD: Twenty HA-coated and 20 noncoated titanium implants were divided equally into four groups as HA-coated implant (HA); noncoated implant (NC); HA-coated implant with membrane (HA/M); noncoated implant with membrane (NC/M). All implants were placed 5 mm above the original bone (OB). Collagen membranes were placed over the implants in HA/M and NC/M groups. The animals were sacrificed at 4 weeks (n=5) and 8 weeks (n=5). Vertical bone height above OB (VBH, mm) and augmented bone area (ABA, mm(2) ) were analyzed histologically and radiographically. RESULTS: At 4 weeks, VBH reached significantly higher level in HA/M group compared with other three groups (p<0.05). At 8 weeks, significant difference was detected between HA/M and NC groups (p<0.05). At 4 and 8 weeks, ABA in HA/M group was significantly larger compared with other three groups (p<0.05). CONCLUSION: The present results indicated that sputtered HA-coated titanium implant together with collagen membrane could be a novel and effective approach for vertical bone augmentation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.
Chou, J, Hao, J, Hatoyama, H, Ben-Nissan, B, Milthorpe, B & Otsuka, M 2015, 'Effect of biomimetic zinc-containing tricalcium phosphate (ZnTCP) on the growth and osteogenic differentiation of mesenchymal stem cells', Journal of Tissue Engineering and Regenerative Medicine, vol. 9, no. 7, pp. 852-858.View/Download from: UTS OPUS or Publisher's site
Several studies have shown the effectiveness of zinc-tricalcium phosphate (Zn–TCP) for bone tissue engineering. In this study, marine calcareous foraminifera possessing uniform pore size distribution were hydrothermally converted to Zn–TCP. The ability of a scaffold to combine effectively with mesenchymal stem cells (MSCs) is a key tissue-engineering aim. In order to demonstrate the osteogenic ability of MSCs with Zn–TCP, the scaffolds were cultured in an osteogenic induction medium to elicit an osteoblastic response. The physicochemical properties of Zn–TCP were characterized by XRD, FT–IR and ICP–MS. MSCs were aspirated from rat femurs and cultured for 3 days before indirectly placing four samples into each respective well. After culture for 7, 10 and 14 days, osteoblastic differentiation was evaluated using alizarin red S stain, measurement of alkaline phosphatase (ALP) levels, cell numbers and cell viability. XRD and FT–IR patterns both showed the replacement of CO32– with PO43–. Chemical analysis showed zinc incorporation of 5 mol%. Significant increases in cell numbers were observed at 10 and 14 days in the Zn–TCP group, while maintaining high levels of cell viability (> 90%). ALP activity in the Zn–TCP group was statistically higher at 10 days. Alizarin red S staining also showed significantly higher levels of calcium mineralization in Zn–TCP compared with the control groups. This study showed that MSCs in the presence of biomimetically derived Zn–TCP can accelerate their differentiation to osteoblasts and could potentially be useful as a scaffold for bone tissue engineering.
Sahin, YM, Gunduz, O, Bulut, B, Ozyegin, LS, Gokce, H, Agaogullari, D, Chou, J, Kayali, ES, Ben-Nissan, B & Oktar, FN 2015, 'Nano-Bioceramic Synthesis from Tropical Sea Snail Shells (Tiger Cowrie - Cypraea Tigris) with Simple Chemical Treatment', ACTA PHYSICA POLONICA A, vol. 127, no. 4, pp. 1055-1058.View/Download from: UTS OPUS
Yamamoto, M, Nakata, H, Hao, J, Chou, J, Kasugai, S & Kuroda, S 2014, 'Osteogenic Potential of Mouse Adipose-Derived Stem Cells Sorted for CD90 and CD105 In Vitro', STEM CELLS INTERNATIONAL.View/Download from: UTS OPUS or Publisher's site
Chou, J, Austin, C, Doble, P, Ben-Nissan, B & Milthorpe, B 2014, 'Trace elemental imaging of coralline hydroxyapatite by laser-ablation inductively coupled plasma-mass spectroscopy', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, no. 7, pp. 515-520.View/Download from: Publisher's site
Chou, J, Valenzuela, S, Green, DW, Kohan, L, Milthorpe, B, Otsuka, M & Ben-Nissan, B 2014, 'Antibiotic delivery potential of nano and micro porous marine structures derived ß-TCP spheres for medical applications', Nanomedicine, vol. 1, pp. 1-9.View/Download from: UTS OPUS or Publisher's site
This study gives a detailed evaluation of the antibiotic potential of a marine structure-based new
drug delivery system produced by hydrothermally converting foraminifera exoskeletons to b-tricalcium
phosphate (b-TCP) to treat clinical strain Staphylococcus aureus (MW2). Materials & methods: Foraminifera
precursor materials were hydrothermally converted at 250°C for 48 h to produce b-TCP and loaded with
gentamicin sulfate by adsorption for 24 h. The physicochemical properties of the material were characterized
by scanning electron microscopy, powder x-ray diffraction and for pore size distribution profiles. The
antibacterial efficacy of the system was tested for inhibition of S. aureus growth and in vitro cellular
behavior were tested with human osteoblast cells (MG63) for cell viability. Discussion: Pore size distribution
profiles showed that the structure allows the uniform distribution of nanopores of 1.5 nm and micropores
of approximately 5 m. The in vitro release profile indicates an initial burst release of 5% of total
incorporated gentamicin. A time-delayed antibacterial efficacy test was designed to introduce the bacteria
at predetermined time intervals from 0 to 60 min and showed that gentamicin prevents S. aureus grown
in the same culture within 30 min, with no evidence of bacterial regrowth within 24 h. Human osteoblast
cell (MG63) studies showed no detrimental effect on cell viability. Conclusion: In the light of these results
nano- and micro-pores
Chou, J, Hao, J, Kuroda, S, Ben-Nissan, B, Milthorpe, B & Otsuka, M 2014, 'Bone regeneration of calvarial defect using marine calcareous-derived beta-tricalcium phosphate macrosphere', Journal of Tissue Engineering, vol. 5, pp. 1-7.View/Download from: UTS OPUS or Publisher's site
The aim of this study was to examine the bone regeneration properties of beta-tricalcium phosphate hydrothermally converted from foraminifera carbonate exoskeleton in the repair of rat calvarial defect. These natural materials possess unique interconnected porous network with uniform pore size distribution, which can be potentially advantageous. In total, 20 adult male Wistar rats received full-thickness calvarial defect with a diameter of 5 mm. The rate of newly formed bone was measured radiologically by X-ray and micro-computed tomography and by histologic examination. After 2 weeks, the beta-tricalcium phosphate group exhibited full closure of the defect site, while control group remained unrestored at the end of the 6-week experimentation. It was observed that the newly regenerated bone thickened over the course of the experiment in the beta-tricalcium phosphate group. No soft tissue reaction was observed around the beta-tricalcium phosphate implant and the rats remained healthy. These results showed that repair of the calvarial defect can be achieved by biomimetic beta-tricalcium phosphate macrospheres, which hold potential for application as bone grafts for bone augmentation surgeries.
Chou, J, Valenzuela, SM, Santos, J, Bishop, D, Milthorpe, B, Green, DW, Otsuka, M & Ben-Nissan, B 2014, 'Strontium- and magnesium-enriched biomimetic beta-TCP macrospheres with potential for bone tissue morphogenesis', JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, vol. 8, no. 10, pp. 771-778.View/Download from: Publisher's site
Macha, IJ, Ozyegin, LS, Chou, J, Samur, R, Oktar, FN & Ben-Nissan, B 2013, 'An Alternative Synthesis Method for Di Calcium Phosphate (Monetite) Powders from Mediterranean Mussel (Mytilus galloprovincialis) Shells.', Journal of the Australian Ceramics Society, vol. 49, no. 2, pp. 122-128.View/Download from: UTS OPUS
Marine species, such as corals, sea shells and nacres, attract special interest in bioceramics field for bone graft, bone cements and drug delivery applications. Most of the marine structures are made up of pure calcium carbonate (calcite or aragonite) with a very small amount of an organic matrix. In the past the most common way to transform these structures to hydroxyapatite was hydrothermal transformation method. This current work introduces a new approach for producing fine powders of calcium phosphates from Mediterranean mussel (Mytilus galloprovincialis) shells. A comparative study was carried out to investigate the differences of these powders under only hot plate heating and hot plate heating together with ultrasonic agitation while H3PO4 was added. The temperature of the hotplate was kept constant at 80 °C and then, H3PO4 was added drop wise into the solution for 2 hrs. The mixture was then placed into an oven at 100 °C for 24 hrs. They were further calcined at 800 °C for 3 hrs. XRD, FTIR and ICP-MS were used to identify the structure and composition. It was found that the final powders were predominantly monetite, with some tricalcium phosphate as a secondary phase. This relatively simple and efficient method can be easily applied to produce calcium phosphate precursor powders for a range of biomedical applications.
Chou, J, Green, DW, Singh, K, Hao, J, Ben-Nissan, B & Milthorpe, BK 2013, 'Adipose Stem Cell Coating of Biomimetic ß-TCP Macrospheres by Use of Laboratory Centrifuge', BioResearch Open Access, vol. 2, no. 1, pp. 67-71.View/Download from: UTS OPUS or Publisher's site
Biomimetic materials such as coral exoskeletons possess unique architectural structures with a uniform and interconnected porous network that can be beneficial as a scaffold material. In addition, these marine structures can be hydrothermally converted to calcium phosphates, while retaining the original structural properties. The ability of biomaterials to stimulate the local microenvironment is one of the main focuses in tissue engineering, and directly coating the scaffold with stem cells facilitates future potential applications in therapeutics and regenerative medicine. In this article we describe a new and simple method that uses a laboratory centrifuge to coat hydrothermally derived beta-tricalcium phosphate macrospheres from coral exoskeleton with stem cells. In this research the optimal seeding duration and speed were determined to be 1?min and 700 g. Scanning electron micrographs showed complete surface coverage by stem cells within 7 days of seeding. This study constitutes an important step toward achieving functional tissue-engineered implants by increasing our understanding of the influence of dynamic parameters on the efficiency and distribution of stem cell attachment to biomimetic materials and how stem cells interact with biomimetic materials.
Chou, J, Hao, J, Ben-Nissan, B, Milthorpe, BK & Otsuka, M 2013, 'Coral Exoskeletons as a Precursor Material for the Development of Calcium Phosphate Drug Delivery System for Bone Tissue Engineering', Biological & Pharmaceutical Bulletin, vol. 36, no. 11, pp. 1662-1665.View/Download from: UTS OPUS or Publisher's site
With the global rise in aging of populations, the occurrence of osteoporosis will continue to increase. Biomaterial and pharmaceutical scientists continue to develop innovative strategies and materials to address this disease. In this article, we describe a new perspective and approach into the use of coral exoskeletons as a precursor material to synthesize a calcium phosphate-based drug delivery system. Studies detailing the methodology of the conversion methods and the strategies and approach for the development of these novel drug delivery systems are described. Furthermore, in vivo studies in osteoporotic mice using a drug loaded and chemically modified version of the biomimetic delivery system showed significant cortical and cancellous bone increases. These studies support the notion and the rationale for future research and development of the use of coral exoskeletons as materials for drug delivery applications
Chou, J, Ito, T, Otsuka, M, Ben-Nissan, B & Milthorpe, BK 2013, 'Simvastatin-loaded Beta-tCP Drug Delivery System Induces Bone Formation And Prevents Rhabdomyolysis In OVX Mice', Advanced Healthcare Materials, vol. 2, no. 5, pp. 678-681.View/Download from: UTS OPUS or Publisher's site
Bone formation and regeneration is a prolonged process that requires a slow drug release system to assist in the long-term recovery. A drug-delivery system is developed that allows for the controlled release of simvastin, without exhibiting the side effects associated with high concentrations of simvastatin, and is still capable of inducing constant bone formation.
Chou, J, Ito, T, Otsuka, M, Ben-Nissan, B & Milthorpe, BK 2013, 'The Controlled Release Of Simvastatin From Biomimetic Macrospheres', Key Engineering Materials, vol. 529-530, pp. 461-464.View/Download from: UTS OPUS or Publisher's site
Simvastatin has been shown to succesfully stimulate bone regeneration and attention has being focussed on developing appropriate delivery carriers for its release. The challenge of deliverying therapeutic concentration of pharmaceutical compunds has bein
Chou, J, Hao, J, Hatoyama, H, Ben-Nissan, B, Milthorpe, BK & Otsuka, M 2013, 'The therapeutic effect on bone mineral formation from biomimetic zinc containing tricalcium phosphate (ZnTCP) in zinc-deficient osteoporotic mice', PLoS One, vol. 8, no. 8, pp. e71821-e71821.View/Download from: UTS OPUS or Publisher's site
The aim of this study was to evaluate the therapeutic efficacy of biomimetic zinc-containing tricalcium phosphate (ZnTCP) produced by hydrothermally converting calcium carbonate exoskeletons from foraminifera, in the treatment of osteoporotic mice. X-Ray powder diffraction showed crystallographic structures matching JCPDS profile for tricalcium phosphate. Mass spectroscopy used to calculate total composition amount showed similar amount of calcium (5×104 µg/g) and phosphate (4×104 ppm) after conversion and the presence of zinc (5.18×103 µg/g). In vitro zinc release showed no release in PBS buffer and <1% zinc release in 7 days. In vivo evaluation was done in ovariectomized mice by implanting the ZnTCP samples in the soft tissues near the right femur bone for four weeks. Thirty ddY mice (5 weeks old, average weight of 21 g) were divided into six experimental groups (normal, sham, OVX, ß-TCP, ZnTCP and direct injection of zinc). CT images were taken every two weeks where the bone mineral density (BMD) and bone mineral content (BMC) were calculated by software based on CT images. The ZnTCP group exhibits cortical and cancellous bone growth of 45% and 20% respectively. While sham, OVX and ß-TCP suffered from bone loss. A correlation was made between the significant body weight increase in ZnTCP with the significant increase in plasma zinc level compared with OVX. The presented results indicate that biomimetic ZnTCP were effective in preventing and treating bone loss in osteoporotic mice model.
Chou, J, Ito, T, Bishop, D, Otsuka, M, Ben-Nissan, B & Milthorpe, B 2013, 'Controlled release of simvastatin from biomimetic -TCP drug delivery system.', PLoS ONE, vol. 8, no. 1, pp. 1-6.View/Download from: UTS OPUS or Publisher's site
Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.
Chou, J, Hao, J, Kuroda, S, Bishop, DP, Ben-Nissan, B, Milthorpe, BK & Otsuka, M 2013, 'Bone regeneration of rat tibial defect by zinc-tricalcium phosphate (Zn-TCP) from porous Foraminifera carbonate macrospheres', Marine Drugs, vol. 11, no. 12, pp. 5148-5158.View/Download from: UTS OPUS or Publisher's site
Foraminifera carbonate exoskeleton was hydrothermally converted to biocompatible and biodegradable zinc-tricalcium phosphate (Zn-TCP) as an alternative biomimetic material for bone fracture repair. Zn-TCP samples implanted in a rat tibial defect model for eight weeks were compared with unfilled defect and beta-tricalcium phosphate showing accelerated bone regeneration compared with the control groups, with statistically significant bone mineral density and bone mineral content growth. CT images of the defect showed restoration of cancellous bone in Zn-TCP and only minimal growth in control group. Histological slices reveal bone in-growth within the pores and porous chamber of the material detailing good bone-material integration with the presence of blood vessels. These results exhibit the future potential of biomimetic Zn-TCP as bone grafts for bone fracture repair.
Green, DW, Padula, M, Santos, J, Chou, J, Milthorpe, BK & Ben-Nissan, B 2013, 'A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration.', Marine Drugs, vol. 11, no. 4, pp. 1203-1220.View/Download from: UTS OPUS or Publisher's site
A vital ingredient for engineering bone tissue, in the culture dish, is the use of recombinant matrix and growth proteins to help accelerate the growth of cultivated tissues into clinically acceptable quantities. The skeletal organic matrices of calcifying marine invertebrates are an untouched potential source of such growth inducing proteins. They have the advantage of being ready-made and retain the native state of the original protein. Striking evidence shows that skeleton building bone morphogenic protein-2/4 (BMP) and transforming growth factor beta (TGF-ß) exist within various marine invertebrates such as, corals. Best practice mariculture and the latest innovations in long-term marine invertebrate cell cultivation can be implemented to ensure that these proteins are produced sustainably and supplied continuously. This also guarantees that coral reef habitats are not damaged during the collection of specimens. Potential proteins for bone repair, either extracted from the skeleton or derived from cultivated tissues, can be identified, evaluated and retrieved using chromatography, cell assays and proteomic methods. Due to the current evidence for bone matrix protein analogues in marine invertebrates, together with the methods established for their production and retrieval there is a genuine prospect that they can be used to regenerate living bone for potential clinical use.
Chou, J, Ben-Nissan, B, Green, DD, Valenzuela, S & Kohan, L 2011, 'Targeting And Dissolution Characteristics Of Bone Forming And Antibacterial Drugs By Harnessing The Structure Of Microspherical Shells From Coral Beach Sand', Advanced Engineering Materials, vol. 13, no. 1-2, pp. 93-99.View/Download from: UTS OPUS or Publisher's site
Pharmaceutical drugs for the treatment of metabolic bone diseases lead to a number of side effects due to the their uncontrollable dispersion throughout the body.() Therefore, many groups directed their research to develop devices that are targeted to
Chou, J, Green, DW & Ben-Nissan, B 2010, 'New slow drug delivery materials and systems for biomedical applications', Materials Australia, vol. 43, no. 3, pp. 37-41.View/Download from: Publisher's site
Chou, J, Shimmon, R & Ben-Nissan, B 2009, 'Bisphosphonate determination using H-1-NMR spectroscopy for biomedical applications', Journal Of Tissue Engineering And Regenerative Medicine, vol. 3, no. 2, pp. 92-96.View/Download from: UTS OPUS or Publisher's site
Bisphosphonate is known to be a very active drug in the treatment of osteoporosis and bone regeneration. A new method has been developed, utilizing nuclear magnetic resonance spectroscopy to identify and measure the amount of bisphosphonate in solution. A standard reference with similar functional group to that of the bisphosphonate was chosen and applied in the experimentation. The results showed that the use of nuclear magnetic resonance spectroscopy (H-1-NMR) in determining the solvent residues of various pharmaceutical drugs has proved to be effective. Unlike chromatography, it is possible to use a universal reference standard as an internal standard assayed by quantitative NMR. Using the same theory, this method is capable of both identifying and quantifying the bisphosphonate in various solutions. This paper is the first publication showing this unique measurement method, which can be used in a range of pharmaceutical and biomedical applications.
Chou, J, Ben-Nissan, B, Choi, AH, Wuhrer, R & Green, D 2007, 'Conversion of coral sand to calcium phosphate for biomedical applications', Journal of the Australasian Ceramic Society, vol. 43, no. 1, pp. 44-48.View/Download from: UTS OPUS
Coral sand grains were analysed using simultaneous differential thermogravimetric analysis (DTA/TGA) Fourier-Transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) and environmental scanning electron microscopy (ESEM). These techniques were performed to confirm the characteristics and properties as well as the composition of the coral sand grains. Imaging of the full surface topography were conducted inthe ESEM. After characterisation coral sand grains were treated for impurities and organic materials were subsequently removed. The materials were then converted to calcium phosphates utilising hydrothermal treatment. The results have shown that the coral sand grains were composed of calcium carbonate with a network of uniform inner porous structure. The ESEM has provided valuable information through the imaging of the samples which in turn allowed a comparison of the pore sizes before and after the hydrothermal treatment. The current study shows that the coral sand to be a promising source of converted calcium carbonate to calium phosphates for biomedical applications.
Chou, J & Hao, J 2016, 'Marine biomaterials as drug delivery system for osteoporosis and bone tissue regeneration' in Handbook of Bioceramics and Biocomposites, Springer, Germany, pp. 1309-1332.View/Download from: UTS OPUS or Publisher's site
© Springer International Publishing Switzerland 2016.There is currently an urgent need to develop sustainable and therapeutically relevant advanced drug delivery systems to treat the prevalence of ongoing human diseases and ailments. The effectiveness of such system will depend primarily on the properties and characteristics of the carrier material. In this chapter, marine materials are investigated as potential drug delivery carriers for bone tissue engineering and in the treatment of osteoporosis. This chapter will explore the unique structures of marine materials that set it apart from its synthetic counterparts and the conversion to biocompatible calcium phosphates combined with synthetic modifications, and case studies will demonstrate the potential clinical applications.
Ben-Nissan, B, Choi, AH, Green, DW, Latella, BA, Chou, J & Bendavid, A 2011, 'Synthesis and Characterization of Hydroxyapatite Nanocoatings by Sol-Gel Method for Clinical Applications' in Sam Zhang (ed), Biological and Biomedical Coatings Handbook: Processing and Characterization, CRC Press, United States, pp. 37-79.View/Download from: UTS OPUS
Nanostructured materials are associated with a diversity of uses within the medical field, for instance, in drug-delivery systems, regenerative medicine, formation of surgical tools, medical devices, and diagnostic systems. It has long been established that porous bulk hydroxyapatite (HAp) cannot be used for load-bearing applications due to its unfavorable mechanical properties. As a result, HAp has been used instead as a coating in orthopedic surgery on metallic alloys, metals giving the support required. Of the metallic alloys used, titanium-based and cobalt chromium alloys are the preferred materials for these HAp coatings for orthopedic and maxillofacial implants (Figure 2.1).
Green, D, Padula, M, Santos, J, Chou, J, Milthorpe, BK & Ben-Nissan, B 2012, 'A new role for marine skeletal proteins in regenerative orthopaedics', Key Engineering Materials (Volumes 529 - 530) bioceramics 24, Bioceramics, Scientific.net, Fukuoka, Japan, pp. 654-659.View/Download from: Publisher's site
Use of ready-made marine skeletons is one of the simplest possible remedies to major problems hindering the future development of regenerative orthopaedics- such as, providing a richness of framework designs and now a potentially rich, accessible source
Harvard Medical School
Massachusetts Institute of Technology (MIT)
Harvard Center for Nanoscale System
Wyss Institute for Biologically Inspired Engineering
Tokyo Medical and Dental University