Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan 030024, People's Republic of China.
Central Hospital of Tongchuan Mining Bureau, Tongchuan 727000, People's Republic of China.
Biomed Mater. 2022 Jul 22;17(5). doi: 10.1088/1748-605X/ac80e3.
Orthopedic implants have been used clinically to restore the functions of the compromised bone tissues, but there is still a relatively high risk of failure for elderly people. A critical reason is pro-inflammatory immune microenvironment created by senescent macrophages with homeostasis imbalance impairs osteogenesis and angiogenesis, two major processes involved in implant osseointegration. The present work proposes to use resveratrol as an autophagy inducing agent to upregulate the autophagy level of senescent macrophages to restore homeostasis, consequently generating a favorable immune microenvironment. The results show 0.1-1 μM of resveratrol can induce autophagy of senescent macrophages, promote cell viability and proliferation, reduce intracellular reactive oxygen species level, and polarize the cells to pro-healing M2 phenotype. The immune microenvironment created by senescent macrophages upon resveratrol stimulation can promote osteogenesis and angiogenesis, as manifested by upregulated proliferation, alkaline phosphatase activity, type I collagen secretion, and extracellular matrix mineralization of senescent osteoblasts as well as nitric oxide production, migration, andangiogenesis of senescent endothelial cells. In addition, resveratrol-loaded silk fibroin coatings can be fabricated on titanium surface through electrophoretic co-deposition and the coatings show beneficial effects on the functions of senescent macrophages. Our results suggest resveratrol can be used as surface additive of titanium implants to promote osseointegration of elderly people though regulating immunology of senescent macrophages.
骨科植入物已在临床上用于恢复受损骨组织的功能，但老年人的植入物失败风险仍然相对较高。一个关键原因是衰老巨噬细胞引起的促炎免疫微环境失衡，破坏了成骨和血管生成这两个主要涉及植入物骨整合的过程。本工作提出使用白藜芦醇作为自噬诱导剂，上调衰老巨噬细胞的自噬水平以恢复平衡，从而产生有利的免疫微环境。结果表明，0.1-1 μM 的白藜芦醇可以诱导衰老巨噬细胞自噬，促进细胞活力和增殖，降低细胞内活性氧水平，并将细胞极化为有利于愈合的 M2 表型。衰老巨噬细胞在白藜芦醇刺激下产生的免疫微环境可以促进成骨和血管生成，表现为衰老成骨细胞的增殖、碱性磷酸酶活性、I 型胶原分泌和细胞外基质矿化增加，以及衰老内皮细胞的一氧化氮产生、迁移和血管生成增加。此外，通过电泳共沉积可以在钛表面制备负载白藜芦醇的丝素蛋白涂层，该涂层对衰老巨噬细胞的功能具有有益的作用。我们的结果表明，白藜芦醇可以用作钛植入物的表面添加剂，通过调节衰老巨噬细胞的免疫学来促进老年人的骨整合。
