Abstract：
The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.
摘要：
骨质疏松性骨缺损的治疗仍然是一个巨大的临床挑战，因为骨质疏松症（OP）与氧化应激和高水平的活性氧（ROS）有关。对骨骼形成有害的条件。抗氧化纳米材料如硒纳米颗粒(SeNPs)由于其多效药理活性而对骨生成具有积极作用,其可以发挥抗氧化应激功能以防止骨丢失并促进OP中的骨再生。在当前的研究中，通过将聚（乳酸-碳酸酯）（PDT）和β-磷酸三钙（β-TCP）与SeNP引入一锅法的策略，是用来准备注射剂的，防崩溃,形状适应性和粘性骨移植替代材料（PDT-TCP-SE）。PDT-TCP-SE骨移植替代品在生物微环境中表现出足够的粘附力和骨诱导活性，血管生成作用和抗炎以及抗氧化作用在体外和体内。此外，PDT-TCP-SE可以通过Sirt1/Nrf2/GPX4抗氧化通路保护骨髓间充质干细胞免受erastin诱导的铁凋亡,which,在一起,证明了骨移植替代材料是一种新兴的生物材料，具有潜在的临床应用前景。重要声明：可注射，防崩溃,粘合剂,塑料和生物活性骨移植替代物成功合成。通过调节骨质疏松性骨缺损区域的氧化应激，将SeNPs与PDT结合到β-TCP原位再生新骨中。PDT-TCP-SE骨移植替代物降低了骨质疏松性骨缺损微环境中的高ROS水平。骨移植替代物还可以通过体外Sirt1/Nrf2/GPX4途径减轻氧化应激并抑制铁性凋亡。此外，PDT-TCP-SE骨移植替代物能缓解体内骨质疏松性骨缺损的炎症环境,促进骨再生。这种生物材料具有合成简单的优点,生物相容性，防崩溃,可注射,和调节氧化应激水平，在骨组织工程中具有潜在的应用价值。
