Development of novel living material by regulation of angiogenesis

• Project/Area Number: 19390510
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: KOYAMA Hiroyuki The University of Tokyo, 医学部・附属病院, 特任准教授 (10241994)
• Co-Investigator(Kenkyū-buntansha): CHIKAZU Daichi 東京大学, 医学部・附属病院, 講師 (30343122) ; MORI Yoshiyuki 東京大学, 医学部・附属病院, 准教授 (70251296) ; OBA Makoto 東京大学, 医学部・附属病院, 特任助教 (20396716) ; YONEHARA Hiroyuki 東京大学, 医学部・附属病院, 准教授 (00251299)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2009: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2008: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 口腔外外科一般 / 血管新生 / マテリアル / スカフォールド / 塩基性線維芽細胞増殖因子 / トマテリアル / スカフォール / 再生骨

Research Abstract

組織血流の確保は、組織の生存性や修復能力を高めるための鍵である。本研究では血管新生誘導能をもつ多機能型の新規足場マテリアルとしてスポンジ状材料とゲル状材料を開発し、動物への埋植実験を通じて最適化を実施した。これらを皮膚欠損や骨欠損の動物モデルに適応して、その治療効果を確認した。また、薬剤徐放マテリアルを応用して血管新生因子の効率的デリバリーを目的とした新規ドラッグデリバリー・システムを開発し、動物モデルを用いた修復組織への血管網誘導実験に成功した。

Research Products

• [Journal Article] Antiangiogenic gene therapy of solid tumor by systemic injection of polyplex micell es loading plasmid DNA encoding soluble flt-1 (2010)
  • Author(s): Oba M, Koyama H, Kataoka K, et al.
  • Journal Title: Mol Pharm. 7 (2) Pages: 201-509
• [Journal Article] Improvement in Wound Healing by a Novel Synthetic Collagen-gel Dressing in Genetically Diabetic Mice (2010)
  • Author(s): Chikazu D., Koyama H., et al
  • Journal Title: Asian Journal of Oral and Maxillofacial Surgery (In press)
  • Peer Reviewed
• [Journal Article] The growth of a vascular net work insi de a coll agen-citric acid derivative hydrogel in rats (2009)
  • Author(s): Takayama T, Taguchi T, Koyama H, et al.
  • Journal Title: Biomaterials 30 (21) Pages: 3580-3587
• [Journal Article] Selective and sustained delivery of basic fibrobl ast growth factor (bFGF) for treatment of peripheral arterial disease : results of a phase I trial (2009)
  • Author(s): Hashimoto T, Koyama H, Miyata T, at al.
  • Journal Title: Eur J Vasc Endovasc Surg. 38 Pages: 71-75
  • NAID: 10026912168
• [Journal Article] Exvivo gene delivery of ephrin-B2 induces devel opment of functional coll ater al vessel sinarabbit model of hind limb ischemia (2009)
  • Author(s): Katsu M, Koyama H, Maekawa H, et al.
  • Journal Title: J Vasc Surg 49 Pages: 192-198
• [Journal Article] Environment-responsive block copolymer micelles with a disul fide cross-linked core for enhanced si RNA delivery (2009)
  • Author(s): Matsumoto S, Oba M, Koyama H, et al.
  • Journal Title: Biomacromol ecules 10 Pages: 119-127
• [Journal Article] The growth of a vascular network inside a collagen-citric acid derivative hydrogel in rats (2009)
  • Author(s): Takayama T., Koyama H., et al
  • Journal Title: Biomaterials 30 Pages: 3580-3587
  • Peer Reviewed
• [Journal Article] Selective and sustained delivery of basic fibroblast growth factor(bFGF)for treatment of peripheral arterial disease : results of a phase I trial. (2009)
  • Author(s): Hashimoto T., Koyama H., et al
  • Journal Title: European Journal of Vascular & Endovascular Surgery 38 Pages: 71-75
  • NAID: 10026912168
  • Peer Reviewed
• [Journal Article] Controlled delivery of bFGF remodeled vascular network in muscle flap and increased perfusion capacity viaminor pedicle (2008)
  • Author(s): Yasuda Y., Koyama H., Oba M, et al.
  • Journal Title: Journal of Surgical Research 147 (1) Pages: 132-7
• [Journal Article] Controlled delivery of bFGF to recipient bed enhances the vascul arization and viability of an ischemic skin flap (2008)
  • Author(s): Fujihara Y., Koyama H., Ohba M, et al
  • Journal Title: Wound Repair & Regeneration 16 (1) Pages: 125-31
• [Journal Article] Polyplexes from poly (aspartamide) bearing 1, 2-diaminoet hane si de chains induce pH-selective, endosomal membrane dest abilization with amplified transfection and negligible cytotoxicity (2008)
  • Author(s): Miyata K., Oba M., Koyama H, et al.
  • Journal Title: Journal of the American Chemical Society 130 (48) Pages: 16287-94
• [Journal Article] Polyplex micelles with cyclic RGD peptide ligands and disulfide cross-links directing to the enhanced transfection via controlled intracellular trafficking (2008)
  • Author(s): Oba M., Koyama H., Kataoka K, et al.
  • Journal Title: Molecular Pharmaceutics 5 (6) Pages: 1080-92
• [Journal Article] Polyplex micelles fromtri block copolymers composed of tandemly aligned segment with biocompatible, endosomal escaping, and DNA condensing functions for systemic gene delivery to pancreatic tumor tissue (2008)
  • Author(s): Miyata K., Oba M., Koyama H, et al.
  • Journal Title: Pharmaceutical Research 25 (12) Pages: 2924-36
• [Journal Article] PEG-det achable polyplex micelles based on disulfide-linked block catiomers as bior esponsive nonviral gene vectors (2008)
  • Author(s): Takae S., Oba M., Koyama H, et al.
  • Journal Title: Journal of the American Chemical Society 130 (18) Pages: 6001-9
• [Journal Article] Controlled delivery of bFGF remodeled vascular network in muscle flap and increased perfusion capacity via minor pedicle. (2008)
  • Author(s): Yasuda Y. Koyama H. Oba M. et al
  • Journal Title: Journal of Surgical Research 147 Pages: 5163-6
  • Peer Reviewed
• [Journal Article] Polyplex micelles from triblock copolymers composed of tandemly aligned segments with biocompatible, endosomat escaping, and DNA condensing functions for systemic gene delivery to pancreatic tumor tissue. (2008)
  • Author(s): Miyata K. Oba M. Koyama H. et al
  • Journal Title: Pharmaceutical Research. 25 Pages: 2924-36
  • Peer Reviewed
• [Journal Article] Charge-conversion ternary polyplex with endosome disruption moiety: a to chnique for efficient and safe gene delivery. (2008)
  • Author(s): Lee Y. Oba M. Koyama H. et at
  • Journal Title: Angewandte Chemie. International Ed. In English. 47 Pages: 5163-6
  • Peer Reviewed
• [Journal Article] Controlled delivery of bFGF remodeled vascular network in muscle fiap and increased perfusion capacity via minor pedicle (2008)
  • Author(s): Yasuda Y, Koyama H, et. al.
  • Journal Title: Journal of Surgical Research (in press)
  • Peer Reviewed
• [Journal Article] Controlled Delivery of bFGF to Recipient Bed Enhances Vascularization and Viability of Ischemic Skin Flap (2008)
  • Author(s): Fujiwara Y, Oba M, Koyama H, et. al.
  • Journal Title: Wound Repair and Regeneration (in press)
  • NAID: 10031181445
  • Peer Reviewed
• [Journal Article] Biocompatible Micellar nanovectors achieve efficient gene transfer to vascular lesions without cytotoxi city and thrombus formation (2007)
  • Author(s): Akagi D, Koyama H, Miyata T, et al
  • Journal Title: Gene Therapy 14 Pages: 1029-1038
• [Journal Article] Cyclic RGD petide-conjugated polyplex micelles as a target able gene dilivery system directed to cells possessing avb3 and avb5 integrins (2007)
  • Author(s): Oba M, Koyama H, et al
  • Journal Title: Bioconjugate Chemistry 18 Pages: 1415-1423
• [Journal Article] Study of quantitative aminolysis reaction poly(ロ-benzyl L-aspartate) (PBLA) as a platform polymer for functionality materials (2007)
  • Author(s): Oba M, Koyama H, et. al.
  • Journal Title: Reactive & Functional Polymers 18 Pages: 1361-1372
  • Peer Reviewed
• [Presentation] 立体的な組織の再生を目指した血管誘導ゲルの開発 (2010)
  • Author(s): 服部理恵子, 小山博之, ら
  • Organizer: 日本再生医療学会、第9回総会、口演
  • Place of Presentation: 広島
  • Year and Date: 2010-03-18
• [Presentation] The Technological State and Prospect for Three-dimensional Complex Organ Structures (2008)
  • Author(s): 小山博之
  • Organizer: Bio Japan 2008
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-16
• [Presentation] bFGF蛋白の経動脈的ピンポイントデリバリー法による血管再生療法 (2008)
  • Author(s): 橋本拓也, 小山博之, ら
  • Organizer: 日本血管外科学会、第36回総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2008-04-18