Yamamoto Masaya, Takahashi Yoshitake, Tabata Yasuhiko
Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawara-cho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Biomaterials. 2003 Nov;24(24):4375-83. doi: 10.1016/s0142-9612(03)00337-5.
The objective of this study is to develop a carrier for the controlled release of bone morphogenetic protein-2 (BMP-2) suitable for enhancement of the bone regeneration activity. Hydrogels with different water contents were prepared through glutaraldehyde crosslinking of gelatin with an isoelectric point of 9.0 under varied reaction conditions. Following subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled BMP-2 into the back of mice, the in vivo retention period of BMP-2 prolonged with a decrease in the water content of hydrogels used, although every time period was much longer than that of BMP-2 solution injection. Ectopic bone formation studies demonstrated that the alkaline phosphatase (ALP) activity and osteocalcin content around the implanted site of BMP-2-incorporated gelatin hydrogels were significantly high compared with those around the injected site of BMP-2 solution. The values became maximum for the gelatin hydrogel incorporating BMP-2 with a middle period of BMP-2 retention, while bone formation was histologically observed around the hydrogel incorporating BMP-2. The ALP activity was significantly higher than that of the collagen sponge incorporating BMP-2. We concluded that the controlled release technology of BMP-2 for a certain time period was essential to induce the potential activity for bone formation.
本研究的目的是开发一种用于骨形态发生蛋白-2（BMP-2）控释的载体，以增强骨再生活性。通过在不同反应条件下用戊二醛交联等电点为9.0的明胶，制备了具有不同含水量的水凝胶。将掺入125I标记的BMP-2的明胶水凝胶皮下植入小鼠背部后，尽管每个时间段都比注射BMP-2溶液的时间长得多，但随着所用凝胶水含量的降低，BMP-2在体内的保留期延长。异位骨形成研究表明，与BMP-2溶液注射部位周围相比，掺入BMP-2的明胶水凝胶植入部位周围的碱性磷酸酶（ALP）活性和骨钙素含量显著更高。对于BMP-2保留中期的掺入BMP-2的明胶水凝胶，这些值达到最大值，同时在掺入BMP-2的水凝胶周围组织学观察到骨形成。其ALP活性显著高于掺入BMP-2的胶原海绵。我们得出结论，BMP-2在一定时间段内的控释技术对于诱导骨形成的潜在活性至关重要。
