Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. Here novel nanofibrous spongy microspheres (NF-SMS) are used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. NF-SMS are shown to significantly enhance the MSC seeding, proliferation and differentiation over control microcarriers. Furthermore, a hyperbranched polymer (HP) with negligible cytotoxicity and high microRNA (miRNAs) binding affinity is synthesized. The HP can complex with anti-miR-199a and self-assemble into “double shell” polyplexes which are able to achieve high transfection efficiency into MSCs. A double-emulsion technique is used to encapsulate these polyplexes in biodegradable nanospheres (NS) to enable sustained anti-miR-199 delivery. Our results demonstrate that MSC/HP-anti-miR-199a/NS/NF-SMS constructs can promote the nucleus pulposus (NP) phenotype and resist calcification in vitro and in a subcutaneous environment. Furthermore, injection of MSC/HP-anti-miR-199a/NS/NF-SMS can stay in place, produce functional extracellular matrix, maintain disc height and prevent intervertebral disc (IVD) calcification in a rabbit lumbar degeneration model.

腰痛主要由椎间盘退变引起，其中经常涉及钙化。在这里，新型纳米纤维海绵状微球 (NF-SMS) 用于携带兔骨髓间充质基质细胞 (MSC) 以再生髓核组织。与对照微载体相比，NF-SMS 显示出显着增强 MSC 的接种、增殖和分化。此外，合成了一种具有可忽略不计的细胞毒性和高 microRNA (miRNA) 结合亲和力的超支化聚合物 (HP)。HP 可以与抗 miR-199a 复合并自组装成“双壳”复合物，从而能够实现向 MSC 的高转染效率。使用双乳液技术将这些复合物封装在可生物降解的纳米球 (NS) 中，以实现持续的抗 miR-199 递送。在体外和皮下环境中。此外，注射 MSC/HP-anti-miR-199a/NS/NF-SMS 可以在兔腰椎退变模型中保持原位，产生功能性细胞外基质，维持椎间盘高度并防止椎间盘 (IVD) 钙化。