The treatment of osteoporotic implant failures tends to be challenging due to an imbalance in bone homeostasis. Recently, the accumulation of intracellular reactive oxygen species (ROS) and activation of the inflammasome containing nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) protein have been shown to indirectly affect osteogenesis and osteoclastogenesis. Owing to the release of multi-metal ions from laponite (LAP), we fabricated a multifunctional LAP coating on a three-dimensional microporous sulfonated polyetheretherketone (SPEEK) surface via polydopamine (PDA) modification (SPEEK@PDA-LAP). The balance between osteogenesis and osteoclastogenesis was examined using macrophages in an osteo-immune microenvironment. Employing assays, we showed that the SPEEK@PDA-LAP alleviated intracellular ROS accumulation and inhibited the activation of NLRP3 inflammasome-mediated pyroptosis in macrophages, creating an osteoimmunomodulatory microenvironment to stimulate osteogenesis and inhibit osteoclastogenesis. The micro-computed tomography and histological results of experiments indicated that SPEEK@PDA-LAP implants reversed the balance between osteogenesis and osteoclastogenesis to promote the formation of new bone around the implant even under osteoporotic conditions. The results indicate that inhibiting the NLRP3 inflammasome and regulating intracellular ROS in macrophages can be an effective therapy for osteoporosis. These results highlight the potential of functional PEEK materials for bone regeneration in patients with osteoporosis.

中文翻译：

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功能化微孔磺化聚醚醚酮：通过ROS和NLRP3介导的巨噬细胞焦亡的成骨和抗破骨细胞生成作用

由于骨稳态失衡，骨质疏松性植入失败的治疗往往具有挑战性。最近，细胞内活性氧（ROS）的积累和含有核苷酸结合寡聚化结构域样受体家族pyrin结构域3（NLRP3）蛋白的激活已被证明可以间接影响成骨和破骨细胞生成。由于锂皂石（LAP）释放多金属离子，我们通过聚多巴胺（PDA）修饰在三维微孔磺化聚醚醚酮（SPEEK）表面制备了多功能LAP涂层（SPEEK@PDA-LAP）。在骨免疫微环境中使用巨噬细胞检查成骨和破骨细胞生成之间的平衡。通过检测，我们发现SPEEK@PDA-LAP减轻了细胞内ROS的积累，并抑制了巨噬细胞中NLRP3炎性体介导的细胞焦亡的激活，创造了骨免疫调节微环境来刺激成骨并抑制破骨细胞生成。显微计算机断层扫描和组织学实验结果表明，SPEEK@PDA-LAP植入物逆转了成骨和破骨细胞生成之间的平衡，即使在骨质疏松条件下也能促进植入物周围新骨的形成。结果表明，抑制NLRP3炎症小体并调节巨噬细胞内的ROS可以成为治疗骨质疏松症的有效方法。这些结果凸显了功能性 PEEK 材料用于骨质疏松症患者骨再生的潜力。