2001 Fiscal Year Final Research Report Summary
Basic research to develop technology for practical use of BMP in less invasive orthopaedic surgery
| Project/Area Number |
11357015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Shinshu University |
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Principal Investigator |
TAKAOKA Kunio Shinshu Univ., Dept. of Orthopaedic Surjery, Professor, 医学部・整形外科学, 教授 (30112048)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Takao Taki Chemicals Central Research Institute, Senior Staff, 開発本部研究所, 有機化学グループ長
SHIMIZU Tominaga Shinshu Univ., Dept. of Orthopaedic Surgery, Assistant Professor, 医学部・附属病院・整形外科, 助手 (40283270)
SAITO Naoto Shinshu Univ., Dept. of Orthopaedic Surgery, Assistant Professor, 医学部・整形外科学, 講師 (80283258)
NOZAKI Kazutoshi Yamanouchi Pharmaceutical Co. Pharmacological Research Center, Senior Staff, 創薬研究本部, 主任研究員
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| Project Period (FY) |
1999 – 2000
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| Keywords | bone morphogenetic protein / osteogenesis / less invasive surgery / synthetic carrier material / biodegradable polymer |
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| Research Abstract |
Bone morphogenetic proteins ( BMPs ) constitute a group of protein retained in bone and accepted as molecules responsible for regenerating potential of bone. In 1988, cDNAs of two BMP molecules ( BMP-2 and BMP-4 ) were cloned and bio synthesized by DNA recombination techniques ( recombinant human BMPs, rhBMPs .). The successful synthesis of the rhBMP provides us potential use of the molecules in medical field to repair damaged bone without bone grafting. However, there remain several problems to be solved for the use of the BMP in clinical practice; 1. lack of optimal drug delivery system or carrier materials for safe and effective use of the BMP molecules; 2. low reponsiveness to BMP in humans. In order to address these issue, we aimed to develop new optimal carrier materials for BMP, new modalities to enhance biological action of BMP and technology to deliver the BMP/ carrier complex to required parts of body in less invasive way. Results currently achieved are as follows.
1. Syntheti
… More
c polymers ( poly-lactic acid/polyethylene glycol block co-polymers, PLA-PEGs ), which are substituting to animal-derived collagen currently utilized as carrier material for BMP, were successfully developed. These polymers have semi-liquid or gel nature and can be selected depending on practical requirements.
2. Anterior thoratic spinal fusion was obtained in dogs by injecting semi-liquid polymer combined with 1mg BMP-2 in 8 weeks, though the surgical techniques for injecting the composite implant remain to be improved and are currently on going.
3. Large intercalated bone defects in humeri of rabbits and in tibiae of dogs were successfully repaired by new bone formation when the defects were replaced with titanium mesh cylinders impregnated with the BMP/polymer composite in 6-8 weeks.
4. Daily indection of Rolipram, a inhibitor to phosphodiesterase-4 was found to enhance the responsiveness to BMP and consequently increased new bone mass induced by BMP. Screening for agents with such effects are under way. Less
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[Publications] Saitou,N., Okada,T., Horiuchi,H., Murakami,N., Takahashi,J., Nawata,M., Ota,H., Nozaki,K. and Takaoka,K.: "A biodegradable polymer as a cytokine delivery system for inducing bone formation"Nature Biotechnology. 19 ( in press ). (2001)
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[Publications] Saitoh,S., Hata,Y., Murakami,N., Seki,H., Miyauchi,S. and Takaoka,K.: "Ectopic calcification following tibial fracture: property analysis"Skeletal Radiology. 29. 609-612 (2000)
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[Publications] Kinoshita,T., Kobayashi,S., Ebara,S., Yoshimura,Y., Horiuchi,H., Tsutsumimoto,T., Wakabayashi,S. and Takaoka,K.: "Phosphodiesterase inhabitors, pentoxyfylline and rolipram, increase bone mass mainly by promoting bone formation in normal mice"Bone. 27. 811-817 (2000)
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[Publications] Kamimura,M., Ebara,S., Kinoshita,T., Itoh,H., Nakakohji,T., Takaoka,K., Ohtsuka,K.: "Anterior surgery with short fusion using the Zielke procedure for thoracic scoliosis; Focus on the correction of compensatory curves"J. Spinal Dysorders. 12. 451-460 (1999)
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[Publications] Kobayashi,S., Shimizu,T., Mehdi,R., Nawata,S., Kojima,S., Tsutsumimoto,T., Iorio,R., Takaoka,K.: "Advantage of concurrent use of ansbolic and antiresorptive agents over single use of these agents in increasing trabecular bone volume, connectivity, and biochemical competence of rat vertebrace"Bone. 25. 703-712 (1999)
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