School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.
Southern University of Science and Technology Hospital, Shenzhen, 518055, China.
J Mater Chem B. 2022 Jun 1;10(21):4020-4030. doi: 10.1039/d2tb00120a.
The high failure risk of endosseous titanium implants under diabetes conditions appeals to strengthen the osteointegration on the titanium-bone (Ti-B) interface. Melatonin (MT) is a neurohormone involved in bone homeostasis, which can promote osteogenesis and inhibit ROS overproduction through multiple pathways, but its effects on the Ti-B interface in diabetes remain elusive. The biodegradable poly(lactic--glycolic acid) (PLGA) has excellent controlled and sustained release properties, low cytotoxicity, and biocompatibility. Our study fabricated a nanofiber in which MT was encapsulated in PLGA to generate a nanofiber coating on a polydopamine (PDA)-modified titanium surface using electrospinning technology. The surface characteristic showed that MT was fully encapsulated in the PLGA carrier, and PLGA@MT was strongly coupled to the titanium matrix. Furthermore, the PLGA@MT-Ti nanofiber could release MT for at least 30 days. cellular tests demonstrated that PLGA@MT-Ti directly stimulates osteogenesis on the Ti-B interface by activating the BMP-4/WNT pathway in a dose-dependent manner. The effect of suppressing diabetes-induced ROS overproduction and promoting cell proliferation was not proportional to the content of MT. experiments revealed that PLGA@MT-Ti screws promoted the bone formation and osteointegration in type 1 diabetes mellitus (T1DM) mice with tibial bone defects. Our findings demonstrate that PLGA@MT-Ti exerted dual effects through activating the BMP-4/WNT pathway and attenuating ROS overproduction to promote osteogenesis and osteointegration at the Ti-B interface, providing a novel strategy to fabricate biomaterial modification and biofunctionalization under diabetic conditions.
在糖尿病条件下，骨内钛种植体的高失败风险促使人们加强钛-骨（Ti-B）界面的骨整合。褪黑素（MT）是一种参与骨稳态的神经激素，它可以通过多种途径促进成骨和抑制 ROS 过度产生，但它在糖尿病条件下对 Ti-B 界面的影响仍不清楚。可生物降解的聚（乳酸-乙醇酸）（PLGA）具有优异的控制和持续释放性能、低细胞毒性和生物相容性。我们的研究通过静电纺丝技术，在聚多巴胺（PDA）修饰的钛表面上制备了一种包裹 MT 的纳米纤维，生成了一种 PLGA 纳米纤维涂层。表面特性表明 MT 完全包裹在 PLGA 载体中，并且 PLGA@MT 与钛基质紧密结合。此外，PLGA@MT-Ti 纳米纤维至少可以持续释放 30 天的 MT。细胞试验表明，PLGA@MT-Ti 通过 BMP-4/WNT 通路的激活，以剂量依赖的方式直接刺激 Ti-B 界面的成骨作用。抑制糖尿病引起的 ROS 过度产生和促进细胞增殖的效果与 MT 的含量不成正比。实验表明，PLGA@MT-Ti 螺钉在胫骨骨缺损的 1 型糖尿病（T1DM）小鼠中促进了骨形成和骨整合。我们的研究结果表明，PLGA@MT-Ti 通过激活 BMP-4/WNT 通路和减轻 ROS 过度产生来发挥双重作用，促进 Ti-B 界面的成骨和骨整合，为在糖尿病条件下制造生物材料改性和生物功能化提供了一种新策略。
