仿生羟磷灰石纳米棒通过 T 细胞衍生的 IL-22 促进骨髓间充质干细胞的成骨作用,加速骨再生。
Biomimetic Hydroxyapatite Nanorods Promote Bone Regeneration Accelerating Osteogenesis of BMSCs through T Cell-Derived IL-22.
机构信息
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai 200125, China.
The Key Laboratory for Ultrafine Materials of Ministry of Education, Engineering Research Centre for Biomedical Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
出版信息
ACS Nano. 2022 Jan 25;16(1):755-770. doi: 10.1021/acsnano.1c08281. Epub 2022 Jan 10.
Manipulations of morphological properties of nanobiomaterials have been demonstrated to modulate the outcome of osteoimmunomodulation and eventually osteogenesis through innate immune response. However, the functions and mechanisms of adaptive immune cells in the process of nanobiomaterials-mediated bone regeneration have remained unknown. Herein, we developed bone-mimicking hydroxyapatite (HAp) nanorods with different aspect ratios as model materials to investigate the impacts of the nanoshape features on osteogenesis and to explore the underlying mechanisms focusing on the functions of T cells and T cell-derived cytokines. HAp nanorods with different aspect ratios (HAp-0, HAp-30, and HAp-100) were implanted into mouse mandibular defect models. Micro-CT and hematoxylin and eosin staining demonstrated that HAp-100 had the best osteogenic effects. Flow cytometry analysis revealed that HAp-100 increased the percentage of T cells in injured mandibles. The osteogenic effects of HAp-100 were significantly blunted in injured mandibles of TCRβ mice. The Luminex xMAP assay and ELISA showed that HAp-100 induced a marked increase of interleukin (IL)-22 in injured mandibles. In cultured T cells, HAp-100 manifested the best capacity to induce the production of IL-22. Conditioned media from HAp-100-primed T cells promoted osteogenesis and JAK1/STAT3 activation in bone marrow stromal cells, all of which were abolished by neutralizing antibodies against IL-22. In summary, bone-mimicking HAp nanorods with different aspect ratios could regulate osteogenesis through modulation of T cells and IL-22 in the bone regeneration process. These findings provided insights for mediation of the immune response of T cells by nanomaterials on osteogenesis and strategies for designing biomaterials with osteoimmunomodulative functions.
纳米生物材料形态特性的调控已被证明可以通过固有免疫反应来调节骨免疫调节的结果,并最终影响成骨。然而,适应性免疫细胞在纳米生物材料介导的骨再生过程中的功能和机制仍不清楚。在此,我们开发了具有不同纵横比的仿生羟基磷灰石(HAp)纳米棒作为模型材料,研究纳米形貌特征对成骨的影响,并探索其内在机制,重点关注 T 细胞的功能及其衍生细胞因子。将不同纵横比的 HAp 纳米棒(HAp-0、HAp-30 和 HAp-100)植入小鼠下颌骨缺损模型中。微 CT 和苏木精-伊红染色表明 HAp-100 具有最佳的成骨效果。流式细胞术分析显示,HAp-100 增加了受损下颌骨中 T 细胞的比例。在 TCRβ 敲除小鼠受损下颌骨中,HAp-100 的成骨作用明显减弱。Luminex xMAP assay 和 ELISA 结果显示,HAp-100 诱导受损下颌骨中白细胞介素(IL)-22 的显著增加。在培养的 T 细胞中,HAp-100 表现出诱导产生 IL-22 的最佳能力。HAp-100 激活的 T 细胞条件培养基促进了骨髓基质细胞的成骨和 JAK1/STAT3 激活,这些作用均被抗 IL-22 中和抗体所阻断。总之,具有不同纵横比的仿生 HAp 纳米棒可通过调节骨再生过程中的 T 细胞和 IL-22 来调节成骨。这些发现为纳米材料对 T 细胞免疫反应的调节和成骨功能的生物材料设计策略提供了新的思路。