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New type of prosthesis combined with rhBMP-2 delivery system

Research Project

Project/Area Number 12671403
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionShinshu University

Principal Investigator

SAITO Naoto  Shinshu University, University Hospital, Assistant Professor, 医学部・附属病院, 講師 (80283258)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Tominaga  Shinshu University, University Hospital, Assistant, 医学部・附属病院, 助手 (40283270)
KOBAYASHI Seneki  Shinshu University, Medical School, Associate Professor, 医学部, 助教授 (40205464)
TAKAOKA Kunio  Shinshu University, Medical School, Professor, 医学部, 教授 (30112048)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsBone morphogenetic protein / Carrier / Drug delivery system / Biodegradable polymer / Hip prosthesis / Bone / サイトカイン
Research Abstract

Total hip arthroplasty is widely accepted for reconstruction of damaged hip joints in spite of potential risk for mechanical loosening and inevitable revision surgery. In such revision surgeries, we often encounter peri-prosthetic bone defects of various grades either in proximal femur or in acetabulum, which often make difficult to obtain stable setting of a new hip prosthesis even if with use of auto- or allogenous bone grafting and various biomaterials. In order to address this problem, we devised new method to repair the bone defect with use of a growth factor bone morphogenetic protein-2 of human type, produced by DNA recombination ( rhBMP-2) in combination with a new synthetic biodegradable Polymer( PLA-DX-PEG ) as a carrier material for the rhBMP-2 delivery. In this report we present the efficacy of the rhBMP-2 retaining prosthesis to reconstruct bone defect in a canine model. In this model, femoral head and medial halfofthe proximal femur was surgically resected to make the bon … More e defect to be repaired. And the prosthesis with partially porous structured Surface which was impregnated with rhBMP-2 ( 100 μ, 500 μ g or 1000 μ g )/PLA-DX-PEG( 100mg ) composite. In control animals, PLA-DX-PEG polymer without rhBMP-2 was packed into the porous surface. New bone formation at the proximal bone defects was examined by routine radiography at 2, 4, 8 and 12 weeks after surgery. In 100, 500μ g and 1,000 μ g rhBMP-2 groups ( n=4 respectively ) definite radiopaque shadows appeared along the bone defects in 4 week and the sizes of the radiopaque area were depended on the rhBMP-2 doses. The radiopaque shadows became more obvious at 8 weeks alter surgery. In control animals, no radiopaque shadow was noted at the bone defect over the experimental period of time. At 12 weeks after surgery, the animals were sacrificed and proximal femurs were harvested. On macroscopic histology and radiology, original bone defects in 500 and 1,000m μ g rhBMP-2 groups were completely repaired and thef prostheses were well fixed within the proximal femurs. In 100 μ g group, the defects were partially repaired with thin new bone. In controls, the defects were left un-repaired and covered by fibrous tissue. On light microscopic examination, the newly formed bone was remodeled to lamellar bone in 12 weeks. In summary, this type of prosthesis combined with rhBMP-2 delivery system might provide us a new modality to restore bone defect or lost bone mass encountered in revision arthroplasty without bone grafting. Less

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Kobayashi S, Saito N, et al.: "Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty"Lancet. 355. 1499-1504 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saito N, et al.: "A biodegradable polymer as a cytokine-delivery system for inducing bone tissues"Nat Biotechnol. 19. 332-335 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saito N, et al.: "Biodegradable poly-D, L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone tissues"J Bone Joint Surg Am. 83. 92-98 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi H, Saito N, et al.: "Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline"Bone. 28. 290-294 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murakami N, Saito N, et al.: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi H, Saito N, et al.: "Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 and a synthetic polymer"J Biomed Mater Res. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takaoka K, et al.: "Biomaterials engineering and devices : human applications, vol 1"The Humana Press, New Jersey. 368 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi,S., Saito,N., et al.: "Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty"Lancet. 355. 1499-1504 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saito,N., et al: "A biodegradable polymer as a cytokine-delivery system for inducing bone tissues"Nat Biotechnol. 19. 332-335 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Saito,N., et al: "Biodegradable poly-D,L-lactic acid-polyethylene glycol block copolymers as a PMP delivery system for inducing bone tissues"J Bone Joint Surg Am. 83. 92-98 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi,H., Saito,N., et al: "Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline"Bone. 28. 290-294 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Horiuchi,H., Saito,N., et al: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Murakami,N., Saito,N., et al: "Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 and a synthetic polymer"J Biomed Mater Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takaoka,K., Saito,N., Miyamoto,S., Okada,T.: "New synthetic degradable polymers as carrier materials for BMP. In Wise DL(ed), Biomaterials engineering and devices: human applications, vol 1"The Humana Press, New Jersey. 239-249 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi S, Saito N, et al.: "Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty"Lancet. 355. 1499-1504 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saito N, et al.: "A biodegradable polymer as a cytokine-delivery system for inducing bone tissues"Nat Biotechnol. 19. 332-335 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saito N, et al.: "Biodegradable poly-D, L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone tissues"J Bone Joint Surg Am. 83. 92-98 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Horiuchi H, Saito N, et al.: "Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline"Bone. 28. 290-294 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Horiuchi H, Saito N, et al.: "Effect of phosphodiesterase inhibitor 4, rolipram, on new bone formations by recombinant human bone morphogenetic protein-2"Bone. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Murakami N, Saito N, et al.: "Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 and a synthetic polymer"J Biomed Mater Res. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Takaoka K., et al.: "Biomaterials engineering and devices : human applications, vol 1"The Humana Press, New Jersey. 368 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi S,Saito N, et al.: "Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty."Lancet. 355. 1499-1504 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita T,Kobayashi S, et al.: "Phosphodiesterase inhibitors, pentoxifylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice."Bone. 27. 811-817 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Saito N, et al.: "A biodegradable polymer as a cytokine-delivery system for inducing bone tissues."Nat Biotechnol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Saito N, et al.: "Biodegradable poly-D, L-lactic acid-polyethylene glycol block copolymers as a BMP delivery system for inducing bone tissues."J Bone Joint Surg Am. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Horiuchi H,Saito N, et al.: "Enhancement of bone morphogenetic protein-2-induced new bone formation in mice by the phosphodiesterase inhibitor pentoxifylline."Bone. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 斎藤直人,高岡邦夫: "骨形成因子(BMP)による骨欠損の修復-BMPのDelivery Systemとして機能する新しい生体分解性ポリマーの開発を中心に."臨整外. 35. 1449-1455

    • Related Report
      2000 Annual Research Report
  • [Publications] Takaoka K, et al.: "Biomaterials engineering and devices : human applications, vol 1"The Humana Press, New Jersey. 368 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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