通过作者查论文: Yasuhiko Tabata

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作者: Yasuhiko Tabata
摘要: A new therapeutic trial based on the self-healing potential of cells to naturally induce tissue regeneration, has been recently noted. To realize this regenerative medical therapy, it is highly required to efficiently combine cells with their local environment which basically allows cells to survive and biologically function in vivo through the essential interaction. Tissue engineering is a biomedical technology or methodology to create the local environment which promotes the proliferation and differentiation of cells to induce tissue regeneration. There are some cases where tissue regeneration can be induced only by supplying a cell scaffold of biomaterials. Drug delivery system (DDS) with biomaterials enhanced the in vivo biological activities of un-stable growth factor and gene for cell-induced tissue regeneration. The controlled release technology enabled growth factors to achieve the regeneration of various tissues experimentally and clinically. The DDS technology also augmented the biological functions of plasmid DNA and small interference RNA. The cells genetically engineered by the DDS gene system showed an enhanced therapeutic efficacy in cell-based tissue regeneration (cell-gene hybrid therapy). By making use of DDS technology, it is possible to suppress the deterioration and proceeding of chronic fibrotic diseases based on the self-healing potential inherently equipped in the living body. This paper emphasizes significance of biomaterials in tissue engineering for regenerative medical therapy.
1467
作者: Junichi Tazaki, Toshiyuki Akazawa, Masaru Murata, Masaya Yamamoto, Yasuhiko Tabata, Ryota Yoshimoto, Makoto Arisue
摘要: Hydroxyapatite (HAp) has been used as a biomaterial for hard tissues. Critical characteristics of biomaterials will include surface geometry, hydrophobicity and hydrophilicity, crystallinity, biodegradation rates, and release pharmacokinetics (PK) of incorporated molecules such as BMP-2. Optimizing BMP-2 for clinical application may be dependent on localized sustained release from biomaterials. We forcused on in vivo local BMP-2 PK and bone induction in two ceramics systems, based on different surface structures. The functionally graded apatites (fg-HAp) was designed by the step-wise calcinations and partial dissolution-precipitation methods. We estimated the in vivo release profile of 125I-labeled BMP-2 from fg-HAp and the dose response of bone induction by BMP-2 in the back subcutis histologically. Bulk-HAp (b-HAp) by only the step-wise calcinations was prepared as a control. The amount of BMP-2 remaining in the fg-HAp at 1 day after implantation was 83.8%, while that was 34.6% in the b-HAp. Moreover, ectopic bone formation were found surely in the fg-HAp/BMP-2 (0.5μg) system at 3 weeks, not in the b-HAp/BMP-2 system. By using fg-HAp, it is likely that an extremely low dose of BMP-2 is enough to enhance bone induction if BMP-2 is appropriately delivered to the site of action.
965
作者: Masaya Yamamoto, Yoshitake Takahashi, Yasuhiko Tabata
摘要: The objective of this study is to examine feasibility of biodegradable gelatin hydrogels incorporating bone morphogenetic protein (BMP)-2 in inducing bone regeneration at a bone defect of non-human primates and rabbits considering their BMP-2 release profiles. As a result, controlled release by the hydrogel system enabled BMP-2 to induce successful bone regeneration in non-human primates even at the BMP-2 dose as low as that for rabbit case (0.034 mg of BMP-2/cm3 of hydrogel).
253
作者: Takuya Ishimoto, Takayoshi Nakano, Yukichi Umakoshi, Masaya Yamamoto, Yasuhiko Tabata
摘要: Bone mechanical function is given as a result of the material and structural parameters of bone tissue. We previously reported that the material parameter of regenerated bone can be evaluated dominantly using two indices of the density and the preferred orientation degree of biological apatite (BAp). In addition, bone morphology remarkably changes during bone regeneration, which may lead to a dynamic change in the mechanical function of whole bone. In this study, therefore, material and structural parameters of regenerated bone are analyzed separately. A 5-mm-long defect was introduced in rabbit ulna and spontaneously regenerated, and then a three-point bending test was conducted at the regenerated portion. The important parameter which dominantly controls the whole bone mechanical function shifts from a structural to material parameter during bone regeneration. Moreover, it was statistically demonstrated that the increase in the material parameter is strongly determined by recovery of the orientation degree of the BAp c-axis.
1451
作者: Marisa Wareechuensook, Yasuhiko Tabata, Sorada Kanokpanont
摘要: Gelatin, a hydrophilic protein derived from collagen, has been widely used in drug delivery system because of its biocompatibility and biodegradability. However, its high water solubility limited its interaction with hydrophilic drugs. The current works propose a method to improve surface activity of gelatin by modifying it into an amphiphilic molecule via conjugating with cholesterol. High contents of cholesterol were conjugated to amino groups (-NH2) of gelatin using N,N’-Disuccinimidyl carbonate. Cholesterol contents were varied from 100% by mole of free -NH2 group in gelatin. The reduction of free -NH2 groups on gelatin determined by 2,4,6-trinitrobenzenesulfonic acid (TNBS) decreased with the increases of cholesterol used in the conjugation. The percentage of reduction of -NH2 content was 74.63 by mole respectively. Hydrophilicity/hydrophobicity changes were evaluated from water and ethylene glycol contact angles. The conjugated-gelatin were aggregated to form micelles at a critical micelle concentration (CMC) of 8 mg/ml in DI water (pH 5), determined by surface tension testing. Average size of the micelles were in range of 459.05±54.59 nm. The micelles were tested for curcumin entrapment for a cancer research.
595
作者: Junichi Tazaki, Toshiyuki Akazawa, Masaru Murata, Masaya Yamamoto, Yasuhiko Tabata, J. Hino, Makoto Arisue, Takanori Shibata
摘要: The aim of this study is to investigate in vivo local BMP-2 PK and bone induction in two bioceramics blocks (HAp, β-TCP), based on different composition and surface structures. We estimated the in vivo release profile of 125I–labeled BMP-2 and bone induction of hard tissues histologically. β-TCP is more effective for both BMP-2 retention and bone induction, compared to HAp, in the ectopic model.
1033
作者: T. Kushibiki, K. Matsumoto, T. Nakamura, Yasuhiko Tabata
摘要: NK4, composed of the NH2-terminal hairpin and subsequent four-kringle domains of hepatocyte growth factor (HGF), acts as a potent angiogenesis inhibitor. This study is an investigation to evaluate the feasibility of controlled release of NK4 plasmid DNA in suppressing tumor growth. Controlled release by a biodegradable hydrogel enabled the NK4 plasmid DNA to enhance the tumor suppression effects. Biodegradable microspheres of cationized gelatin were prepared for the controlled release of a NK4 plasmid DNA. The cationized gelatin microspheres incorporating NK4 plasmid DNA were subcutaneously injected to tumor-bearing mice to evaluate the suppressive effects on tumor angiogenesis and growth. The cationized gelatin microspheres incorporating NK4 plasmid DNA could release over 28 days. When the cationized gelatin microspheres incorporating NK4 plasmid DNA were injected into the subcutaneous tissue of mice intraperitoneally inoculated with pancreatic cancer cells, their survival time period was prolonged. Tumor growth was suppressed to a significantly greater extent than free NK4 plasmid DNA. The controlled release of NK4 plasmid DNA suppressed angiogenesis and increased cell apoptosis in the tumor tissue, while it enhanced and prolonged the serum level of NK4 protein. We conclude that the controlled release technology was promising to enhance the tumor suppression effects of NK4 plasmid DNA.
121
作者: Takayoshi Nakano, Takuya Ishimoto, Jee Wook Lee, Yukichi Umakoshi, Masaya Yamamoto, Yasuhiko Tabata, Akio Kobayashi, Hiroyoshi Iwaki, Kunio Takaoka, Mariko Kawai, Toshio Yamamoto
摘要: A dominant inorganic substance in hard tissue is known to be a biological apatite (BAp)^nano-crystal which basically crystallizes in an anisotropic hcp lattice, and the BAp c-axis is parallel to extended collagen fibrils. We applied the microbeam X-ray diffractometer system with an incident beam spot 100µm or 50µm in diameter to the original, regenerated and pathological hard tissues in order to analyze the preferential alignment of the BAp c-axis as a parameter of bone quality closely relating to the mechanical function. We conclude that the BAp orientational distribution in the hard tissues is a new measure to evaluate stress distribution in vivo, nano-scale microstructure and the related mechanical function, healing process of the regenerated bone and progress of the bone diseases.
255
作者: K. Yingsukwattana, S. Agthong, R. Mongkonnavin, Yasuhiko Tabata, Sorada Kanokpanont
摘要: Currently, most commercialized peripheral nerve regenerative products are constructed from biodegradable polymers into hollow conduits. To speed up the regeneration rate, we proposed a development of a biocompatible protein-filled conduit for anastomosis amputated peripheral nerve with growth factor controlled release function. Glutaraldehyde-crosslinked protein sponges were tested for their abilities to controlled release of nerve growth factor (NGF) in vitro in our previous experiments. Type B gelatin sponges were able to limit diffusions of NGF due to electrostatic interactions between them. The rate of growth factor releases would be depended on degradation of the crosslinked gelatin. A nerve conduit model was produced using perfluoro alkoxy (PFA) tubes filled with gelatin which had been crosslinked using X-ray from Argon plasma treatment. This method of crosslinking provided 21.22±3.03 % degree of crosslinking. Hollow nerve conduits fabricated from poly(l-lactide-co-caprolactone) (PLCL) had a thicknesses and an inner diameters of 0.31±0.03 mm and 1.63±0.07 mm respectively. Average pore sizes of the inner surfaces and outer surfaces were 9.70±3.44 µm and 1.24±0.77 µm respectively. PLCL film supported growth of L929 mouse fibroblasts. For continuing works, we are testing the protein-filled conduits for peripheral nerve regeneration in animals.
701
作者: Jee Wook Lee, Takayoshi Nakano, Satoru Toyosawa, Yasuhiko Tabata, Yukichi Umakoshi
摘要: Bone microstructure and its functions are maintained by the activity of bone cells such as osteoclast for bone resorption and osteoblast for bone formation. In this study, we examined the role of osteoclast on the formation of the preferential orientation of biological apatite (BAp) as a bone quality parameter using OPG-KO and op/op mouse models in which the expression of osteoclast increases for osteoporosis and decreases for osteopetrosis. The orientation degree of the BAp c-axis was analyzed by a microbeam X-ray diffraction system. We found more decrease in the preferential alignment of the BAp c-axis along the longitudinal direction of bone in the femoral bones of both OPG-KO and op/op mice at 12 weeks compared with normal control mice. We concluded that changes in the amount and activity of osteoclast affect BAp alignment, resulting in the degradation of bone microstructure in osteoporosis and osteopetrosis.
761
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