| Co-Investigator(Kenkyū-buntansha) |
EBARA Sohei School of Medicine, Shinshu University, Assistant Professor, 医学部・附属病院, 講師 (40176780)
SAITOH Satoru School of Medicine, Shinshu University, Assistant Professor, 医学部・附属病院, 講師 (20175350)
TAKAOKA Kunio School of Medicine, Shinshu University, Professor, 医学部, 教授 (30112048)
SHIMIZU Tominaga School of Medicine, Shinshu University, Assistant, 医学部・附属病院, 助手 (40283270)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The regenerating potential of human bone appears to be limited since the repair of large bone defects, which are often associated with comminuted open fractures or bone tumor resections, is typically not observed in these situations. In these severe cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require surgical procedures. Less-invasive alternative treatments have been sought and one possible approach involves the injection of cytokines with bone inducing capacity, such as bone morphogenetic proteins (BMPs). BMPs are biologically active molecules capable of eliciting new bone formation in vivo. However, previous studies have indicated that injection of a small amount of pure BMP alone is not sufficient to induce new bone formation in situ, probably due to the rapid diffusion of the protein away from the site of injection. Therefore, an effective delivery system must be able to balance the retention and release of the BMP at the implant
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ed site for a period long enough for the protein to exercise its inherent biological activity. The goal of our study was to develop injectable BMP-delivery systems for a minimally invasive treatment of bone defects or fractures.
We tested the suitability for BMP-delivery systems of synthetic biodegradable polymer, a poly-D,L-lactic acid-polyethylene glycol block copolymer (PLA-PEG) with tissue-compatiblity and degradablity. Four types of polymers with various molecular weights (<10,000) of PLA and PEG were synthesized. These were PLA1500-PEG600 (P2100), PLA2200-PEG1000 (P3200),PLA4400-PEG2000 (P6400), and PLA6500-PEG3000 (P9500). A comparison of these four polymers indicated that, even though the total molecular weight was altered substantially, almost the same ratio of PLA to PEG (approximately 60 to 40) was maintained. P9500 was difficult to inject when the temperature is lower than 80℃. On the other hand, P2100 had the most suitable properties for an injectable drug delivery system because of its high fluidity at low temperature. But the Ca content of the bone formed by P2100 was significantly low, probably due to the rapid diffusion of this polymer away from the site of injection. P3200 and P6400 were considered to be more suitable for injectable delivery systems for BMPs. When heated, they can be injected percutaneously with a syringe, thus avoiding the need for surgical implantation. Subsequently, they become firm when they cool down to body temperature, resulting in solid polymeric implants in the body. Moreover, surgery is not required for their removal because of their biodegradability. It is therefore concluded that these two types of PLA-PEG/BMP composite are suitable for injectable osteoinductive material which can be used, for example, in the treatment of large osseous defects. Less
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