Antisenescence ZIF-8/Resveratrol Nanoformulation with Potential for Enhancement of Bone Fracture Healing in the Elderly.
Zhengjiang XuYuan ZhangDanping LuGuofang ZhangYang LiZu Fu LuFei WangGuocheng WangPublished in: ACS biomaterials science & engineering (2023)
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, H 2 O 2 -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.
Keyphrases
- endothelial cells
- respiratory syncytial virus
- induced apoptosis
- respiratory tract
- oxidative stress
- high glucose
- bone mineral density
- reactive oxygen species
- bone marrow
- dna damage
- cell cycle arrest
- single cell
- endoplasmic reticulum stress
- soft tissue
- cell therapy
- mesenchymal stem cells
- cell death
- diabetic rats
- signaling pathway
- body composition
- postmenopausal women
- bone regeneration
- body mass index
- stem cells
- weight gain
- transcription factor
- stress induced
- ionic liquid
- climate change
- drug delivery
- anti inflammatory