基于钛亲和性生物模拟活性肽双向调控骨形成和骨吸收促进钛植入材料骨整合效应的研究

提高植入物（如钛基材料）与周边组织的骨整合性是骨科患者治疗中的关键问题。通过引入生物活性分子有效调节骨形成和骨吸收平衡，对于提高钛植入材料的骨整合性，特别是特殊临床症状下（如骨质疏松症）的稳定性具有重要的意义。BMP-2关节肽为BMP-2蛋白的活性序列，具有活性稳定和易于化学改性的优点。本项目将具有成骨活性的BMP-2关节肽与前期研发的钛亲和性仿生肽结合，设计出新型钛亲和性成骨肽，可“一步法”将BMP-2活性引入钛植入材料表面。基于此，研究改性表面的理化特征和生物相容性；同时，建立大鼠骨质疏松症模型，探讨改性表面BMP-2肽对不同骨代谢状态下成骨细胞和破骨细胞的活化调控作用，评估改性钛钉植入体内后BMP-2肽双向调控骨形成和骨吸收对骨整合的影响，阐明BMP-2肽促进骨整合的作用机制。此项研究可为临床应用BMP-2肽及在不同骨代谢状态下实施促进钛植入材料骨整合的新策略提供实验基础和理论依据。

The improvement of osseointegration and enhancement of new bone formation at the interface of medical implants (e.g., Titanium biomaterials) are crucial in the orthopedic surgery treatment. Efficient regulating the balance of bone formation and bone resorption on titanium-based implants by introduction of bioactivity, especially in the osteoporosis patients, is of great significance for clinical stability of the established Ti implants. BMP-2 knuckle peptide, the bioactive sequence of BMP-2 protein, possesses obvious advantages including stable bioactivity and the flexibility for chemical modification. In this project, we will develop a novel biomimetic peptide based on BMP-2 knuckle peptide and the titanium-binding peptide we previously reported. The new biomimetic titanium-binding bioactive peptide could be easily used for one-step modification of Ti implants. Besides the surface properties and biocompatibility of the grafted titanium implants, we will also give detailed study on the effects on regulating mesenchymal stem cell-derived osteoblast differentiation and macrophage-derived osteoclast formation in vitro. In addition, to explore the mechanism between bone formation and bone resorption in vivo, the rat model with osteoporosis will be studied. In short, this project will provide both theoretical and experimental foundations on the development of efficient BMP-2 mimetic peptides for improved osseointegration of titanium-based implants under different bone metabolism conditions.