Yang Minggang, Zhang Yufan, Hou Zhenhao, Wu Jianbo, Liu Fuwei, Wu Jun, Yeung Kelvin W K, Qian Wenhao, Liu Xuanyong, Kong Liang, Li Yunpeng, Qiu Jiajun, Wang Guocheng
Research Center for Human Tissues & Organs Degeneration, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, 710032, China.
Adv Healthc Mater. 2025 May;14(12):e2500743. doi: 10.1002/adhm.202500743. Epub 2025 Mar 27.
Antibiotic therapy is a key strategy for treating infections associated with orthopedic implants, yet its limited effectiveness and potential to disrupt bone healing highlight the need for innovative approaches. Herein, a TiO-Graphene (TiO-G) metastructure is developed on Ti implant surface using a hydrothermal method coupled with plasma-enhanced chemical vapor deposition (PECVD), showing strong near-infrared light (NIR) absorption. The antibiotic doxycycline (DOX) is successfully loaded onto TiO-G and exhibited enhanced NIR release. The promising antibacterial efficacy is proven by both in vitro and in vivo tests with NIR irradiation for 5 min, which is ascribed to the synergistic photocatalytic activity of TiO-G and NIR-responsive release of DOX. Interestingly, after 5 min of NIR irradiation, the TiO-G metasurface neutralized the immediate negative effects of photodynamics and even upregulated the expression of osteogenic genes (osteocalcin (OPN), osteopontin (BSP), and bone sialoprotein (OCN)), with particularly enhanced effects observed on day 14. Moreover, the sustained release function of TiO-G significantly mitigated the cytotoxicity of free antibiotics with antibacterial capabilities comparable to those of TiO-G/DOX under NIR irradiation for 5 min. Consequently, the in vivo studies proved that the TiO-G metastructure enhanced the osteointegration of the implant even in the absence of infection when loaded with DOX.
抗生素治疗是治疗与骨科植入物相关感染的关键策略,但其有效性有限且可能干扰骨愈合,这凸显了创新方法的必要性。在此,采用水热法结合等离子体增强化学气相沉积(PECVD)在钛植入物表面制备了一种TiO-石墨烯(TiO-G)亚结构,该结构显示出强烈的近红外光(NIR)吸收。抗生素强力霉素(DOX)成功负载到TiO-G上,并表现出增强的近红外释放。通过体外和体内试验证明,在近红外照射5分钟后具有良好的抗菌效果,这归因于TiO-G的协同光催化活性和DOX的近红外响应释放。有趣的是,在近红外照射5分钟后,TiO-G超表面抵消了光动力学的即时负面影响,甚至上调了成骨基因(骨钙素(OPN)、骨桥蛋白(BSP)和骨唾液蛋白(OCN))的表达,在第14天观察到特别增强的效果。此外,TiO-G的缓释功能显著减轻了游离抗生素的细胞毒性,其抗菌能力与近红外照射5分钟下的TiO-G/DOX相当。因此,体内研究证明,即使在没有感染的情况下,当负载DOX时,TiO-G亚结构也能增强植入物的骨整合。