Wei Yaojie, Liu Zhongqun, Zhu Xu, Jiang Le, Shi Weidong, Wang Yingjin, Xu Nan, Gang Fangli, Wang Xiumei, Zhao Lingyun, Lin Jun, Sun Xiaodan
State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, People's Republic of China; Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, People's Republic of China.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215000, People's Republic of China.
Biomaterials. 2020 Oct;257:120237. doi: 10.1016/j.biomaterials.2020.120237. Epub 2020 Jul 13.
Peri-implant aseptic inflammation and osteolysis can cause aseptic loosening, leading to the failure of implants. Therefore, aseptic loosening of orthopedic implants remains an imminent problem for the development of durable and effective implants. In this work, a common anti-inflammatory drug (aspirin, ASA) was loaded in poly(lactic-co-glycolic acid) (PLGA) to construct nanofiber coatings on titanium (Ti) via electrospinning. The adhesion of the nanofiber coatings to Ti was ensured by polydopamine (PDA) modification. A stable and sustainable release of aspirin from the nanofiber coatings could last up to 60 days. Such electrospun PLGA@ASA nanofiber coatings could promote proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) as well as inhibit M1 polarization and RANKL-induced osteoclast differentiation of macrophages in vitro. These results indicated that this facile formulation of the PLGA@ASA nanofiber coatings for long-term drug release could be expected to address the problem of aseptic loosening effectively in dual directions of both anti-inflammation and improving osseointegration simultaneously. Notably, the in vivo experiments demonstrated that PLGA@ASA nanofiber coatings did promote osseointegration ability of Ti implants significantly, even in challenging condition with wear particles, and also effectively inhibited Ti particle induced osteolysis around the implants. This work indicates a promising way for the development of durable and effective implants by using PLGA@ASA-PDA-Ti to address the problem of aseptic loosening in dual directions.
种植体周围无菌性炎症和骨溶解可导致无菌性松动，进而导致种植体失效。因此，骨科植入物的无菌性松动仍然是耐用且有效的植入物发展面临的紧迫问题。在这项工作中，将一种常见的抗炎药物（阿司匹林，ASA）负载于聚乳酸-羟基乙酸共聚物（PLGA）中，通过静电纺丝在钛（Ti）上构建纳米纤维涂层。通过聚多巴胺（PDA）改性确保纳米纤维涂层与Ti的附着力。纳米纤维涂层中阿司匹林的稳定可持续释放可持续长达60天。这种静电纺丝的PLGA@ASA纳米纤维涂层在体外可促进骨髓间充质干细胞（BMSC）的增殖和成骨分化，并抑制巨噬细胞的M1极化以及RANKL诱导的破骨细胞分化。这些结果表明，这种用于长期药物释放的PLGA@ASA纳米纤维涂层的简便配方有望在抗炎和改善骨整合这两个方向上有效解决无菌性松动问题。值得注意的是，体内实验表明，即使在存在磨损颗粒的挑战性条件下，PLGA@ASA纳米纤维涂层也确实显著促进了Ti植入物的骨整合能力，并且还有效抑制了植入物周围Ti颗粒诱导的骨溶解。这项工作为通过使用PLGA@ASA-PDA-Ti在两个方向上解决无菌性松动问题来开发耐用且有效的植入物指明了一条有前景的道路。
