School of Medicine, Southeast University, Nanjing, 210009, China.
Jiangsu Key Laboratory for Biomaterials and Devices, Southeast University, Nanjing, 210096, China.
Adv Healthc Mater. 2022 Sep;11(17):e2200602. doi: 10.1002/adhm.202200602. Epub 2022 Jul 7.
Osteochondral defects are characterized by injuries to both cartilage and subchondral bone, which is a result of trauma, inflammation, or inappropriate loading. Due to the unique biological properties of subchondral bone and cartilage, developing a tissue engineering scaffold that can promote dual-lineage regeneration of cartilage and bone simultaneously remains a great challenge. In this study, a microporous nanosilicate-reinforced enzymatically crosslinked silk fibroin (SF) hydrogel is fabricated by introducing montmorillonite (MMT) nanoparticles via intercalation chemistry. In vitro studies show that SF-MMT nanocomposite hydrogel has improved mechanical properties and hydrophilicity, as well as the bioactivities to promote the osteogenic differentiation of bone marrow mesenchymal stem cells and maintain chondrocyte phenotype compared with SF hydrogel. Global proteomic analysis verifies the dual-lineage bioactivities of SF-MMT nanocomposite hydrogel, which are probably regulated by multiple signaling pathways. Furthermore, it is observed that the biophysical interaction of cells and SF-MMT nanocomposite hydrogel is partially mediated by clathrin-mediated endocytosis and its downstream processes. In vivo, the SF-MMT nanocomposite hydrogel effectively promotes osteochondral regeneration as evidenced by macroscopic, micro-CT, and histological evaluation. In conclusion, a functionalized SF-MMT nanocomposite hydrogel is developed with dual-lineage bioactivity for osteochondral regeneration, indicating its potential in osteochondral tissue engineering.
软骨下骨缺损的特征是软骨和软骨下骨同时受伤，这是创伤、炎症或不当负荷的结果。由于软骨下骨和软骨的独特生物学特性，开发一种能够同时促进软骨和骨的双谱系再生的组织工程支架仍然是一个巨大的挑战。在这项研究中，通过插层化学方法引入蒙脱土（MMT）纳米颗粒，制备了一种具有微孔纳米硅酸盐增强的酶交联丝素（SF）水凝胶。体外研究表明，与 SF 水凝胶相比，SF-MMT 纳米复合材料水凝胶具有改善的机械性能和亲水性，以及促进骨髓间充质干细胞成骨分化和维持软骨细胞表型的生物活性。全局蛋白质组学分析证实了 SF-MMT 纳米复合材料水凝胶的双谱系生物活性，这可能是由多种信号通路调节的。此外，观察到细胞与 SF-MMT 纳米复合材料水凝胶的生物物理相互作用部分是由网格蛋白介导的内吞作用及其下游过程介导的。在体内，SF-MMT 纳米复合材料水凝胶通过宏观、微 CT 和组织学评估有效地促进了软骨下骨再生。总之，开发了具有双谱系生物活性的功能化 SF-MMT 纳米复合材料水凝胶用于软骨下骨再生，表明其在软骨下骨组织工程中的潜力。
