新型自组装甲状旁腺素小分子多肽的筛选优化及其治疗骨质疏松性骨缺损的研究

如何研制具有良好“骨诱导活性”和“精巧分级结构”，同时还具有抗骨质疏松能力的仿生骨修复材料是当前骨组织工程研究亟待解决的关键问题之一。.本项目拟在以往长期从事多肽研究的基础上，进一步运用多肽筛选及控释技术和两亲性多肽自组装矿化原理，筛选优化获得序列更简洁的PTH小分子活性肽（pPTH），克服前期研究PTH成骨序列小分子活性肽生物学活性不够稳定和活性位点暴露不充分的缺点；然后利用肽键进一步稳定pPTH的空间结构并缓慢控释，研制出具有良好骨诱导活性的纳米纤维凝胶/β-磷酸三钙多孔仿生骨修复材料。.本设计通过可自组装矿化的两亲性多肽与β-磷酸三钙多孔陶瓷材料的复合获得了和天然骨相似的分级结构；更重要的是通过pPTH的控释获得了骨再生急需的骨诱导活性以及抗骨质疏松能力，在一定程度上解决了当前骨修复材料研究的关键问题，也为我国率先研发出具有自主知识产权的抗骨质疏松药物奠定一定基础。

How to develop a biomimetic bone repair material with good osteoinductive activity and fine grading structure and ability of anti-osteoporosis is one of the key problems in bone tissue engineering research..In this project, based on the long-term research on peptides, we further use the principles of polypeptide screening and controlled release technology and amphiphilic polypeptides self-assembly mineralization to select the more suitable PTH small peptides to overcome disadvantages of PTH peptide（pPTH）unstable enough and inadequate exposure of active sites. Then, the peptide structure was used to.stabilize the space structure of the pPTH and to release controlled slowed, and then the nanofiber gel / β-tricalcium phosphate biomimetic bone with good osteoinductive activity was prepared..In this design, the amphiphilic peptides with self-assembling mineralized and β-tricalcium phosphate ceramic have similar structures to the natural bone. More importantly, the osteoinductive activity of bone regeneration is obtained through the controlled release of pPTH, as well as anti-osteoporosis ability. To a certain extent, it was to solve the current key issues on bone repair materials, but also the first developed with independent intellectual property rights of anti-osteoporosis drugs laid a foundation.