假体周围炎性骨溶解（PPO）是导致人工关节置换术（TJA）后失败的重要原因之一。我们针对PPO发生的关键环节，设计合成钛亲和性仿生肽(DOPA)4-S5-RGDS。相关预实验证实该多肽可以有效缓解PPO，并在抑制integrin-αvβ3表达的同时，调控M1型巨噬细胞向M2型转化，据此我们提出假说：钛亲和性仿生肽可以靶向结合integrin-αvβ3调控巨噬细胞极化抑制慢性炎症反应从而抑制PPO的发生。我们利用大鼠PPO模型和临床标本检测PPO后integrin-αvβ3的定位与变化，同时通过siRNA干扰及基因转染技术等技术检测巨噬细胞表型及关键细胞因子，以验证该假说。本项目从动物水平到临床水平，兼顾体内、体外的立体式研究，为提高关节假体置换预后效果、延长人工关节假体寿命提供新思路。

In the microenvironment of peri-implant inflammation, excessive polarization of pro-inflammatory M1 phenotype macrophages lead to a large amount of secretion of inflammatory cytokines that promotes bone resorption and limits osteogenesis around implants. This process will eventually lead to the failure of prosthetic implants for aseptic loosening. To reverse prosthesis loosening caused by inflammation, we synthesized a mussel-inspired peptide (DOPA)4‐S5-GRGDS, which is capped with quadri-groups of DOPA and an Arg-Gly-Asp (RGD) sequence. This peptide can easily modify the surface of medical titanium implant materials by immersing in (DOPA)4‐S5-GRGDS solution. We found that modified titanium-based implant can effectively inhibit peri-implant inflammation induced by wear-particle and transform polarization of macrophages into pro-healing M2 phenotype by interfering with integrin-αvβ3.In order to verify this hypothesis, we used XPS, AFM to determine its modification characterization. We established an osteolysis model to verify its effect on PPO. Western blot, RT-PCR, siRNA interference and gene transfection techniques were used to detect the macrophage phenotype and key cytokines, confirming the mechanism of integrin-targeted peptide-modified titanium-based materials to regulate macrophage polarization and inhibit PPO. Considering the simplicity of modification of the titanium metal surfaces, the highly biomimetic characteristics of the peptide, and the efficient increase in osteogenesis under inflammatory conditions, the (DOPA)4-S5-GRGDS peptide is a suitable candidate for the prevention and treatment of prosthesis loosening.