研究者詳細 - 井川　和代

菊池泰裕, 吉本高志, 渡邉一夫, 瀬戸皖一, 晴山雅人, 今井茂樹, 井川和代

月刊新医療 41 ( 12 ) 53 - 57 2014年

記述言語：日本語出版者・発行元：(株)エムイー振興協会

ホウ素中性子捕捉療法(BNCT)は、腫瘍に集積するホウ素薬剤を患者に投与した後に中性子線を腫瘍に照射する。腫瘍内に集積したホウ素が中性子を捕捉してヘリウム原子核とリチウム原子核に分裂し、これらの粒子が粒子線として腫瘍内部から狭い範囲に照射される。原子炉でないと施行できなかった本治療を一般病院で利用できるように開発、治験が進められている。BNCTは、治療困難な悪性腫瘍の予後改善に寄与することが期待される。(著者抄録)

J-GLOBAL

犬におけるテーラーメイド骨インプラント移植後のトレハロース被覆と塩基性線維芽細胞成長因子による骨再生の変化査読

Choi S, Lee J, Igawa K, Liu IL, Honnami M, Suzuki S, Nishimura R, Chung UI, Sasaki N, Mochizuki M

The Journal of veterinary medical science 75 ( 6 ) 721 - 6 2013年

Development and evaluation of tetrapod-shaped granular artificial bones. 査読国際誌

Sungjin Choi, I-li Liu, Kenichi Yamamoto, Kazuyo Igawa, Manabu Mochizuki, Takamasa Sakai, Ryosuke Echigo, Muneki Honnami, Shigeki Suzuki, Ung-il Chung, Nobuo Sasaki

Acta biomaterialia 8 ( 6 ) 2340 - 7 2012年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

We have developed a novel form of granular artificial bone "Tetrabones" with a homogeneous tetrapod shape and uniform size. Tetrabones are four armed structures that accumulate to form the intergranular pores that allow invasion of cells and blood vessels. In this study we evaluated the physicochemical characteristics of Tetrabones in vitro, and compared their biological and biomechanical properties in vivo to those of conventional β-tricalcium phosphate (β-TCP) granule artificial bone. Both the rupture strength and elastic modulus of Tetrabone particles were higher than those of β-TCP granules in vitro. The connectivity of intergranular pores 100, 300, and 400 μm in size were higher in Tetrabones than in the β-TCP granules. Tetrabones showed similar osteoconductivity and biomechanical stiffness to β-TCP at 2 months after implantation in an in vivo study of canine bone defects. These results suggest that Tetrabones may be a good bone graft material in bone reconstruction.

DOI： 10.1016/j.actbio.2012.02.019

Three-dimensional shape control of implant devices 査読

Ung-Il Chung, Hideto Saijoh, Kazuyo Igawa, Yuki Kanno, Yoshiyuki Mori, Tsuyoshi Takato

Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine 579 - 588 2012年1月

記述言語：英語掲載種別：論文集(書籍)内論文出版者・発行元：Pan Stanford Publishing Pte. Ltd.

The performance of the scaffolds holds a key to the realization of tissue engineering/regenerative medicine in clinical settings. We have focused on the vital role of the dimensional compatibility of the scaffolds. By controlling the three-dimensional (3D) shape of the scaffolds, we have significantly improved the performance of the artificial bones, which have good dimensional compatibility, resultant reduction in the operation time and corresponding invasiveness, and resultant speedy union with the host bone tissues. We conclude that 3D shape control is vital to the performance of the scaffolds.We propose that it is worth considering at least once to attempt to control the 3D shape of the scaffold by optimizing the design and fabrication method, before using expensive and highrisk growth factors and cells. © 2012 Pan Stanford Publishing Pte. Ltd. All rights reserved.

DOI： 10.4032/9789814267861

Scopus

テーラーメイド骨インプラントからの塩基性線維芽細胞成長因子放出に及ぼすトレハロースコーティングの影響査読

Choi S, Lee J, Igawa K, Suzuki S, Mochizuki M, Nishimura R, Chung UI, Sasaki N

The Journal of veterinary medical science 73 ( 12 ) 1547 - 52 2011年12月

Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system. 査読

Hironori Hojo, Fumiko Yano, Shinsuke Ohba, Kazuyo Igawa, Keiji Nakajima, Yuske Komiyama, Akinori Kan, Toshiyuki Ikeda, Takayuki Yonezawa, Je-Tae Woo, Tsuyoshi Takato, Kozo Nakamura, Hiroshi Kawaguchi, Ung-il Chung

Journal of bone and mineral metabolism 28 ( 6 ) 627 - 33 2010年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

To effectively treat degenerative joint diseases including osteoarthritis (OA), small chemical compounds need to be developed that can potently induce chondrogenic differentiation without promoting terminal differentiation. For this purpose, we screened natural and synthetic compound libraries using a Col2GFP-ATDC5 system and identified oxytetracycline (Oxy) as a chondrogenic compound. Oxy induced cartilaginous matrix synthesis and mRNA expressions of chondrocyte markers in ATDC5 cells. In addition, Oxy suppressed mineralization and mRNA expressions of terminal chondrocyte differentiation markers in ATDC5 cells, primary chondrocytes, and cultured metatarsal bones. Oxy's induction of Col2 mRNA expression was decreased by the addition of Noggin and was increased by the addition of BMP2. Furthermore, Oxy increased mRNA expression of Id1, Bmp2, Bmp4, and Bmp6. These data suggest that Oxy induces chondrogenic differentiation in a BMP-dependent manner and suppresses terminal differentiation. Oxy may be useful for treatment of OA and also for regeneration of cartilage tissue.

DOI： 10.1007/s00774-010-0179-y

顎再建における脛骨海綿骨移植、台湾における10年の経験

57 ( supp ) 179 - 187 2010年

Temporal and spatial changes in element distribution in bone and cartilage. 査読

Kenichi Yamamoto, Kazuyo Igawa, Hiroshi Ueno, Fumiko Yano, Ung-Il Chung, Isao Koshima

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 14 ( 2 ) 198 - 203 2009年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

BACKGROUND: Bone and cartilage act as reservoirs for a number of elements, and the perturbation of these elements is suggested to contribute to various diseases. Even so, little is known about their respective temporal and spatial distribution. METHODS: Three knee joints of three mice on the first day after birth, three knee joints of 3-week-old mice, and three knee joints of 20-week-old mice were prepared. We performed element mapping in the bone and cartilage of normal mouse knee joints. We measured element distribution in articular cartilage, trabecular bone, cortical bone, joint cartilage, growth plates, and joint cavities using energy dispersive X-ray spectrometry. RESULTS: The analysis revealed the following: (1) The main elements in articular cartilage of 1-day-old mice were Na, O, P, S, and Ca; and those in bone were Na, O, P, S, K, Ca, and Mg. (2) The main elements in the growth plate of 3-week-old mice were Na, N, O, P, S, Cl, K, and Ca; those in joint cartilage were Na, O, P, S, Cl, and K; and those in bone were Na, O, P, Ca, and Mg. (3) The main elements in the growth plate of 20-week-old mice were Na, O, P, S, Cl, K, and Ca; and those in bone were Na, O, P, S, K, Ca, and Mg. After corrections were made for the Na ratios of these elements, we investigated the temporal and spatial changes in the distribution of each element. On the first day after birth, a spatial change was seen in the growth plate cartilage: the more the cartilage matured toward hypertrophy, the more S and Ca it contained. Temporal changes in element distribution in the growth plate cartilage, articular cartilage, and bone were observed. Growth plate cartilage of the older mice contained more S and Ca than that of the younger mice. Bone of the older mice contained more Ca and Mg than that of the younger mice. Spatial changes in element distribution in the cortical bone were also seen; that is, the more the cortical bone matured toward diaphysis, the more Mg and the less S it contained. In contrast, no temporal or spatial changes in element distribution were observed in the joint space. No significant temporal or spatial changes in the distribution of P, Cl, or K were seen. CONCLUSIONS: These results suggest that element mapping may be useful for identifying the age and maturity of different skeletal tissues. In particular, it may help distinguish between immature cartilage and mature cartilage based on the Ca and S contents.

DOI： 10.1007/s00776-008-1315-6

Maxillofacial reconstruction using custom-made artificial bones fabricated by inkjet printing technology. 査読

Hideto Saijo, Kazuyo Igawa, Yuki Kanno, Yoshiyuki Mori, Kayoko Kondo, Koutaro Shimizu, Shigeki Suzuki, Daichi Chikazu, Mitsuki Iino, Masahiro Anzai, Nobuo Sasaki, Ung-il Chung, Tsuyoshi Takato

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 12 ( 3 ) 200 - 5 2009年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Ideally, artificial bones should be dimensionally compatible with deformities, and be biodegradable and osteoconductive; however, there are no artificial bones developed to date that satisfy these requirements. We fabricated novel custom-made artificial bones from alpha-tricalcium phosphate powder using an inkjet printer and implanted them in ten patients with maxillofacial deformities. The artificial bones had dimensional compatibility in all the patients. The operation time was reduced due to minimal need for size adjustment and fixing manipulation. The postsurgical computed tomography analysis detected partial union between the artificial bones and host bone tissues. There were no serious adverse reactions. These findings provide support for further clinical studies of the inkjet-printed custom-made artificial bones.

DOI： 10.1007/s10047-009-0462-7

Bone regeneration within a tailor-made tricalcium phosphate bone implant with both horizontal and vertical cylindrical holes transplanted into the skull of dogs. 査読

Sung-jin Choi, Jong-il Lee, Kazuyo Igawa, Osamaru Sugimori, Shigeki Suzuki, Manabu Mochizuki, Ryouhei Nishimura, Ung-il Chung, Nobuo Sasaki

Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs 12 ( 4 ) 274 - 7 2009年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

A new tailor-made bone implant (TI) with six horizontal cylindrical holes fabricated from alpha-tricalcium phosphate powder, as described in our previous report, was modified to include five additional vertical holes (TI-v) in an attempt to accelerate the bone regeneration through the holes. This TI-v implant and hydroxyapatite implants (HI) as controls were transplanted into experimental skull defects in dogs. Computed tomography (CT) was performed immediately after the surgery and then every 4 weeks. The dogs were killed for histological analysis at 24 weeks of implantation. On CT, bone bridging between the implant and the skull was observed in the TI-v group from 8 weeks of implantation, whereas a clear bone bridge was not formed in the HI group after 24 weeks of implantation. Histological analysis revealed collagen tissues and new bone formation in the horizontal cylindrical holes in most of the TI-v group, whereas mainly connective tissues invaded the porous structures in the HI group. In the Ti-v group, at the middle of the horizontal holes where they crossed the vertical holes, fibrous collagen tissues and muscular tissue filled up the hole and new bone formation seemed to be blocked. However, in the TI-v group more collagen and bone tissues were formed than in the HI group; when compared with the data in our previous report, however, the total volume of regenerated bone in the horizontal cylindrical holes in the TI-v seemed to be less than that in the TI. Thus, the addition of vertical cylindrical holes in the TI-v was not effective in promoting the faster stabilization of the TI-v in the skull of the dog.

DOI： 10.1007/s10047-009-0474-3

Development of high-throughput screening system for osteogenic drugs using a cell-based sensor. 査読国際誌

Hironori Hojo, Kazuyo Igawa, Shinsuke Ohba, Fumiko Yano, Keiji Nakajima, Yuske Komiyama, Toshiyuki Ikeda, Alexander C Lichtler, Je-Tae Woo, Takayuki Yonezawa, Tsuyoshi Takato, Ung-il Chung

Biochemical and biophysical research communications 376 ( 2 ) 375 - 9 2008年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ACADEMIC PRESS INC ELSEVIER SCIENCE

To effectively treat osteoporosis and other bone-loss disorders, small compounds that potently induce bone formation are needed. The present study initially attempted to establish a monitoring system that could detect osteogenic differentiation easily, precisely, and noninvasively. For this purpose, we established pre-osteoblastic MC3T3E1 cells stably transfected with the GFP reporter gene driven by a 2.3 kb fragment of rat type I collagen promoter (Col1a1GFP-MC3T3E1). Among these cells, we selected a clone that fluoresced upon osteogenic stimulation by BMP2. The GFP fluorescence intensity corresponded well to the intensity of alkaline phosphatase (ALP) staining and to the level of osteocalcin (Oc) mRNA. Using this system, we screened natural and synthetic compound libraries and thus identified an isoflavone derivative, glabrisoflavone (GI). GI induced ALP staining and Oc mRNA in a dose-dependent manner. The Col1a1GFP-MC3T3E1 system may be useful for identifying novel osteogenic drugs.

DOI： 10.1016/j.bbrc.2008.08.167

三次元インクジェットプリンターにより直接的に組み立てたテーラーメイドリン酸三カルシウム骨インプラント(Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer)

井川和代, 望月学, 杉森理, 清水康太郎, 山澤建二, 川口浩, 中村耕三, 高戸毅, 西村亮平, 鈴木茂樹, 安斎正博, 鄭雄一, 佐々木伸雄

人工臓器 37 ( 1 ) 14 - 16 2008年6月

記述言語：日本語出版者・発行元：(一社)日本人工臓器学会

CT画像データを基にα型リン酸三カルシウム(α-TCP)粉体を3Dインクジェットプリンターで直接積層構造形したテーラーメイド人工骨「CT-Bone」を作製し、大動物(ビーグル犬)の骨欠損モデルにおける安全性と有効性について検討した。ビーグル犬は健常な平均1歳10ヵ月齢(11ヵ月齢〜2歳10ヵ月齢、雄3頭・雌4頭)を用い、頭部に左右2ヶ所欠損部位を作成し、右側にCT-Bone,左側に対照群としてハイドロキシアパタイト(HA)を移植した。その結果、CT所見ではCT-Boneのマクロ連通孔の縮小が徐々に進行したが、HAでは変化がみられず、3週目以降CT-Boneでは骨断端との間に骨性架橋形成が認められたがHPでは骨断端の架橋は認められなかった。組織学的にはCT-Boneでは人工骨周囲に広汎な膠原線維の増生と血管の侵入を認め、TRAP染色では人工骨周囲にTRP陽性細胞が認められた。骨断端と人工骨の接合部では連通孔内に膠原線維が侵入しその一部は骨化され、骨髄組織の形成も認められた。HAではその多孔構造内に膠原線維を主体とする組織が侵入する島状の組織が認められ、TRAP染色では膠原線維が人工骨実質と接する部位にTRAP陽性細胞の活性が認められ、膠原線維と人工骨頭の間に僅かながら骨形成を認めた。以上より、インクジェット方式で作製したCT-Boneは骨欠損部位にほぼ完全に合致する形態で作製することができ、従来の人工骨のように徒手切削を必要せず、更に連通孔などの内部構造も自由に付与でき、また粉体を焼結しないため吸収・置換にも優れていた。

Development of an osteoblast-based 3D continuous-perfusion microfluidic system for drug screening. 国際誌

Kihoon Jang, Kae Sato, Kazuyo Igawa, Ung-il Chung, Takehiko Kitamori

Analytical and bioanalytical chemistry 390 ( 3 ) 825 - 32 2008年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

In this work, we demonstrated that biological cells could be cultured in a continuous-perfusion glass microchip system for drug screening. We used mouse Col1a1GFP MC-3T3 E1 osteoblastic cells, which have a marker gene system expressing green fluorescent protein (GFP) under the control of osteoblast-specific promoters. With our microchip-based cell culture system, we realized automated long-term monitoring of cells and sampling of the culture supernatant system for osteoblast differentiation assay using a small number of cells. The system successfully monitored cells for 10 days. Under the 3D microchannel condition, shear stress (0.07 dyne/cm(2) at a flow rate of 0.2 microL/min) was applied to the cells and it enhanced the GFP expression and differentiation of the osteoblasts. Analysis of alkaline phosphatase (ALP), which is an enzyme marker of osteoblasts, supported the results of GFP expression. In the case of differentiation medium containing bone morphogenetic protein 2, we found that ALP activity in the culture supernatant was enhanced 10 times in the microchannel compared with the static condition in 48-well dishes. A combined system of a microchip and a cell-based sensor might allow us to monitor osteogenic differentiation easily, precisely, and noninvasively. Our system can be applied in high-throughput drug screening assay for discovering osteogenic compounds.

骨・軟骨の再生医療UPDATE 三次元プリンティングを用いた人工骨の臨床応用の現状と展望

新時代を拓く化学のキーコンセプトインテリジェント化材料インクジェットプリンターによるインプラントデバイスの高機能化

井川和代, 鄭雄一, 鄭雄一

化学 63 ( 1 ) 2008年

三次元高機能足場の構築

井川和代, CHUNG Ung-il

日本臨床 66 ( 5 ) 820 - 823 2008年

井川和代, CHUNG Ung-il

Clinical Calcium 18 ( 12 ) 1737 - 1743 2008年

記述言語：日本語出版者・発行元：(株)医薬ジャーナル社

先天異常、外傷および術後等による顎顔面重度欠損症に対して、高機能人工骨を創製することにより形態機能回復に関する新たな治療法を確立する。骨の無機成分に近いリン酸三カルシウム(TCP)は、中性付近における水に対する溶解度が高く、生体内で吸収されながら新生骨に置換される生体吸収性の骨修復材料として臨床使用されている。しかし、TCP人工骨は骨伝導能を有するが積極的な骨誘導能を示さない。人工骨の機能性を高めるために、TCP粉体を3Dインクジェットプリンターで造形することで三次元形態を付与した高機能人工骨を作製し、大型動物での有効性と安全性を評価した。(著者抄録)

J-GLOBAL