The purpose of the present study is to modify the polyethylene terephthalate ligament with hydroxyapatite via biomineralization and to investigate its effect on graft-bone healing. After biomineralization of hydroxyapatite, the surface characterization of polyethylene terephthalate ligament was examined by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and water contact angle measurements. The compatibility and osteoinduction, along with the underlying signaling pathway involved of hydroxyapatite-polyethylene terephthalate ligament, were evaluated in vitro. Moreover, a rabbit anterior cruciate ligament reconstruction model was established, and the polyethylene terephthalate or hydroxyapatite-polyethylene terephthalate artificial ligament was implanted into the knee. The micro-computed tomography analysis, histological, and immunohistochemical examination as well as biomechanical test were performed to investigate the effect of hydroxyapatite coating in vivo. The results of scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction showed that the hydroxyapatite was successfully deposited on the polyethylene terephthalate ligament. Water contact angle of the hydroxyapatite-polyethylene terephthalate group was significantly smaller than that of the polyethylene terephthalate group. The in vitro study showed that hydroxyapatite coating significantly improved adhesion and proliferation of MC3T3-E1 cells. The osteogenic differentiation of cells was also enhanced through the activation of ERK1/2 pathway. The micro-computed tomography, histological, and immunohistochemical results showed that biomineralization of hydroxyapatite significantly promoted new bone and fibrocartilage tissue formation at 12 weeks postoperatively. Moreover, the failure load and stiffness in the hydroxyapatite-polyethylene terephthalate group were higher than that in the polyethylene terephthalate group. Therefore, biomineralizaion of hydroxyapatite enhances the biocompatibility and osseointegration of the polyethylene terephthalate artificial ligament, thus promoting graft-bone healing for anterior cruciate ligament reconstruction through the activation of ERK1/2 pathway.

本研究的目的是通过生物矿化用羟基磷灰石改性聚对苯二甲酸乙二醇酯韧带，并研究其对移植骨愈合的影响。在羟基磷灰石生物矿化后，聚对苯二甲酸乙二醇酯韧带的表面特征通过扫描电子显微镜、傅里叶变换红外光谱、X 射线衍射和水接触角测量进行了检查。在体外评估了相容性和骨诱导，以及涉及羟基磷灰石-聚对苯二甲酸乙二醇酯韧带的潜在信号通路。此外，建立兔前交叉韧带重建模型，将聚对苯二甲酸乙二醇酯或羟基磷灰石-聚对苯二甲酸乙二醇酯人工韧带植入膝关节。显微计算机断层扫描分析，进行组织学和免疫组织化学检查以及生物力学测试以研究羟基磷灰石涂层的体内效果。扫描电镜、傅里叶变换红外光谱和X射线衍射结果表明羟基磷灰石成功沉积在聚对苯二甲酸乙二醇酯韧带上。羟基磷灰石-聚对苯二甲酸乙二醇酯组的水接触角明显小于聚对苯二甲酸乙二醇酯组。体外研究表明羟基磷灰石涂层显着改善了MC3T3-E1细胞的粘附和增殖。细胞的成骨分化也通过激活 ERK1/2 通路得到增强。显微计算机断层扫描、组织学、免疫组化结果显示，羟基磷灰石的生物矿化显着促进了术后 12 周新骨和纤维软骨组织的形成。此外，羟基磷灰石-聚对苯二甲酸乙二醇酯组的破坏载荷和刚度高于聚对苯二甲酸乙二醇酯组。因此，羟基磷灰石的生物矿化增强了聚对苯二甲酸乙二醇酯人工韧带的生物相容性和骨整合，从而通过激活ERK1/2通路促进了前交叉韧带重建的移植骨愈合。羟基磷灰石-聚对苯二甲酸乙二醇酯组的破坏载荷和刚度高于聚对苯二甲酸乙二醇酯组。因此，羟基磷灰石的生物矿化增强了聚对苯二甲酸乙二醇酯人工韧带的生物相容性和骨整合，从而通过激活ERK1/2通路促进了前交叉韧带重建的移植骨愈合。羟基磷灰石-聚对苯二甲酸乙二醇酯组的破坏载荷和刚度高于聚对苯二甲酸乙二醇酯组。因此，羟基磷灰石的生物矿化增强了聚对苯二甲酸乙二醇酯人工韧带的生物相容性和骨整合，从而通过激活ERK1/2通路促进了前交叉韧带重建的移植骨愈合。