Chou, J., Ito, T., Otsuka, M., Ben-Nissan, B. & Milthorpe, B.K. 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.
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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.
Macha, I.J., Ozyegin, L., Chou, J., Samur, R., Oktar, F. & Ben-Nissan, B. 2013, 'An alternative synthesis method for di calcium phosphate (monetite) powders from mediterranean mussel (mytilus galloprovincialis) shells', Journal of the Australian Ceramic Society, vol. 49, no. 2, pp. 122-128.
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 degrees C and then, H3PO4 was added drop wise into the solution for 2 hrs. The mixture was then placed into an oven at 100 degrees C for 24 hrs. They were further calcined at 800 degrees 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., Hao, J., Hatoyama, H., Ben-Nissan, B., Milthorpe, B.K. & 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, p. e71821.
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 (5104 g/g) and phosphate (4104 ppm) after conversion and the presence of zinc (5.18103 g/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, -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 -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.
Green, D.W., Padula, M.P., Santos, J., Chou, J., Milthorpe, B.K. & Ben-Nissan, B. 2013, 'A Therapeutic Potential for Marine Skeletal Proteins in Bone Regeneration.', Marine Drugs, vol. 11, no. 4, pp. 1203-1220.
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-) 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., Ito, T., Bishop, D.P., Otsuka, M., Ben-Nissan, B. & Milthorpe, B.K. 2013, 'Controlled Release of Simvastatin from Biomimetic -TCP Drug Delivery System', PLoS One, vol. 8, no. 1, pp. e54676-1-e54676-6.
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., Green, D.W., Singh, K., Ben-Nissan, B. & Milthorpe, B.K. 2013, 'Adipose Stem Cell Coating of Biomimetic -TCP Macrospheres by Use of Laboratory Centrifuge', BioResearch Open Access, vol. 2, no. 1, pp. 67-71.
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, B.K. & 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.
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., Ben-Nissan, B., Green, D.D., 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.
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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, D.W. & Ben-Nissan, B. 2010, 'New slow drug delivery materials and systems for biomedical applications', Materials Australia, vol. 43, no. 3, pp. 37-41.
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.
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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, A.H., 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.
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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.
Lewis, K.C., Choi, A.H., Chou, J. & Ben-Nissan, B. 2007, 'Nanoceramics in medical applications', Materials Australia, vol. 40, no. 3, pp. 32-34.