Abstract：
Bone defects in osteoporosis usually present excessive reactive oxygen species (ROS), abnormal inflammation levels, irregular shapes and impaired bone regeneration ability; therefore, osteoporotic bone defects are difficult to repair. In this study, an injectable thermosensitive hydrogel poly (D, L-lactide)-poly (ethylene glycol)- poly (D, L-lactide) (PLEL) system containing resveratrol (Res) and dexamethasone (DEX) is designed to create a microenvironment conducive to osteogenesis in osteoporotic bone defects. This PLEL hydrogel is injected and filled irregular defect areas and achieving a rapid sol-gel transition in situ. Res has a strong anti-inflammatory effects that can effectively remove excess free radicals at the damaged site, guide macrophage polarization to the M2 phenotype, and regulate immune responses. Additionally, DEX can promote osteogenic differentiation. In vitro experiments showed that the hydrogel effectively promoted osteogenic differentiation of mesenchymal stem cells, removed excess intracellular ROS, and regulated macrophage polarization to reduce inflammatory responses. In vivo experiments showed that the hydrogel promoted osteoporotic bone defect regeneration and modulated immune responses. Overall, this study confirmed that the hydrogel can treat osteoporotic bone defects by synergistically modulating bone damage microenvironment, alleviating inflammatory responses, and promoting osteogenesis; thus, it represents a promising drug delivery strategy to repair osteoporotic bone defects.
摘要：
骨质疏松症的骨缺损通常存在过量的活性氧（ROS），异常炎症水平，不规则的形状和受损的骨再生能力;因此，骨质疏松性骨缺损难以修复。在这项研究中,一种可注射的热敏水凝胶聚(D，L-丙交酯-聚(乙二醇)-聚(D,含有白藜芦醇（Res）和地塞米松（DEX）的L-丙交酯（PLEL）系统旨在创造有利于骨质疏松性骨缺损中成骨的微环境。该PLEL水凝胶被注入并填充不规则缺陷区域,并在原位实现快速的溶胶-凝胶转变。Res具有很强的抗炎作用，可以有效清除受损部位多余的自由基，引导巨噬细胞极化到M2表型，调节免疫反应。此外,DEX可以促进成骨分化。体外实验表明,该水凝胶能有效促进间充质干细胞的成骨分化,去除过量的细胞内ROS，调节巨噬细胞极化以减少炎症反应。体内实验表明，水凝胶促进骨质疏松性骨缺损的再生并调节免疫反应。总的来说,这项研究证实了水凝胶可以通过协同调节骨损伤微环境来治疗骨质疏松性骨缺损，缓解炎症反应，促进成骨；因此，它代表了一种有希望的药物递送策略来修复骨质疏松性骨缺损。
