Research Center for Human Tissues & Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Guangdong 518055, Shenzhen, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
ACS Biomater Sci Eng. 2023 May 8;9(5):2636-2646. doi: 10.1021/acsbiomaterials.3c00090. Epub 2023 Apr 10.
Accumulation of senescent cells in the elderly impairs bone homeostasis. It is important to alleviate cell senescence and scavenge excessive oxidative stress for enhanced bone fracture healing in elderly patients. In this study, resveratrol (RSV), an antioxidant drug, was encapsulated in a biocompatible zeolitic imidazolate framework-8 (ZIF-8) nanoparticle to protect it from oxidation and improve its bioavailability. Cells responsible for bone healing, including osteoblasts, bone marrow-derived mesenchymal stem cells (BMSCs), macrophages, and endothelial cells, were used to evaluate the regulatory role of the nanoformulation in the alleviation of cellular senescence and promotion of cell functions. It was proved that the nanoformulation sustainably released RSV with well-preserved bioactivity and improved bioavailability. Cell experiments confirmed that ZIF-8/RSV was capable of alleviating the senescence of cells [human osteoblasts (HOBs), BMSCs, HO-induced senescent vascular endothelial cells (HUVECs)] and scavenging excessive intracellular reactive oxygen species (ROS). Excitingly, the ZIF-8/RSV improved the osteogenic ability of senescent osteoblasts and promoted macrophage M2 polarization. In addition, the ZIF-8/RSV also enhanced the angiogenic function of senescent HUVECs. More importantly, the ZIF-8/RSV nanoformulation outperformed the REV alone, indicating the critical role of encapsulation using ZIF-8. These findings suggest that the ZIF-8/RSV nanoformulation exhibits potential for bone fracture treatment in elderly patients.
衰老细胞在老年人中的积累会损害骨稳态。对于老年患者增强骨骨折愈合，减轻细胞衰老和清除过多的氧化应激非常重要。在这项研究中，白藜芦醇（RSV），一种抗氧化药物，被包裹在生物相容的沸石咪唑酯骨架-8（ZIF-8）纳米颗粒中，以防止其氧化并提高其生物利用度。负责骨愈合的细胞，包括成骨细胞、骨髓间充质干细胞（BMSCs）、巨噬细胞和内皮细胞，用于评估纳米制剂在减轻细胞衰老和促进细胞功能方面的调节作用。证明了纳米制剂能够持续释放具有良好生物活性和提高生物利用度的 RSV。细胞实验证实，ZIF-8/RSV 能够减轻细胞衰老[人成骨细胞（HOBs）、BMSCs、HO 诱导的衰老血管内皮细胞（HUVECs）]并清除过多的细胞内活性氧（ROS）。令人兴奋的是，ZIF-8/RSV 提高了衰老成骨细胞的成骨能力，并促进了巨噬细胞 M2 极化。此外，ZIF-8/RSV 还增强了衰老 HUVECs 的血管生成功能。更重要的是，ZIF-8/RSV 纳米制剂的表现优于单独的 RSV，表明使用 ZIF-8 进行封装的关键作用。这些发现表明，ZIF-8/RSV 纳米制剂具有治疗老年患者骨骨折的潜力。
