超声协同载仿生制剂SDF-1α@Ir/Ce-MOF@CM复合水凝胶治疗骨关节炎的研究

骨关节炎(OA)是发病率很高的慢性退行性关节疾病，OA软骨过表达的活性氧（ROS）诱发氧化应激与炎症反应，是造成软骨不可逆破坏的重要原因。促进软骨再生是治疗OA的难点，抗炎和干细胞是关键因素。基于贵金属原子掺杂的金属有机框架（MOF）仿酶纳米制剂可有效下调ROS水平、抑制炎症，为干细胞提供合适的微环境。前期我们掌握了超声介导载SDF-1α纳米液粒-凝胶促进内源性干细胞迁移的方法，同时探索了制备仿酶纳米制剂和包覆细胞膜的方法。在本项目中我们拟研究Ir原子掺杂Ce-MOF仿酶纳米制剂的合成，并负载SDF-1α、包覆软骨细胞膜构建仿生制剂（SDF-1α@Ir/Ce-MOF@CM），协同超声和水凝胶支架，调控ROS微环境，促进内源性干细胞向软骨缺损处迁移、增殖和分化，从而抑制OA炎症并促进软骨再生；探讨治疗效果及机制，旨在为OA等慢性退行性关节疾病寻找高效的治疗方式提供理论与实验依据。

Osteoarthritis (OA) is the chronic degenerative disease with a high incidence. The overproduced reactive oxygen species (ROS) in OA cartilage induces severe oxidative stress and inflammation, which is the important cause of irreversible cartilage destruction. The cartilage regeneration is a difficult strategy for OA treatment, and anti-inflammation and stem cells are key factors. Noble metal atom doped the metal-organic frame work (MOF) enzyme-mimic nanomaterials can effectively down-regulate ROS levels and inhibit the inflammatory cytokines, which provides a suitable microenvironment for stem cells. Based on our previous study, ultrasound could mediate SDF-1α nanodroplets-hydrogel to promote the endogenous stem cells migration. Meanwhile, we have explored the bionic technology of preparing enzyme-mimic nanoagents and coating cell membrane. In this project, we propose to study the synthesis of Ir atom-doped Ce-MOF, and construct the bionic nanoagents by loading SDF-1α and coating cartilage cell membrane (SDF-1α@Ir/Ce-MOF@CM), with ultrasound and hydrogel to synergistically regulate the ROS microenvironment and promote endogenous stem cells to the cartilage defects for OA treatment. The therapeutic effect and mechanism will be explored, aiming to provide theoretical and experimental basis for seeking highly efficient new strategies for the treatment of chronic degenerative joint diseases such as OA.