Department of Biomedical Engineering, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510006, China.
National Engineering Research Center for Tissue Restoration and Reconstruction (NERC-TRR), Guangzhou, 510006, China.
Adv Healthc Mater. 2022 Apr;11(8):e2102395. doi: 10.1002/adhm.202102395. Epub 2021 Dec 15.
Owing to the lack of blood vessels, nerves, and lymph, articular cartilage defect is difficult to self-repair. Although several cartilage tissue engineering products have been authorized for clinical use, there are still some problems such as large surgical wounds, weak adhesion with the host tissue, and the limited source of autologous chondrocytes. In this paper, a novel dynamic nanocomposite microgel assembly with excellent microporosity, injectability, tissue-adhesion, and sustained kartogenin (KGN) release is reported. Specifically, KGN-loaded cyclodextrin nanoparticles are synthesized through nanoemulsification and incorporated into bone marrow mesenchymal stem cell (BMSCs)-laden microgels via droplet-based microfluidics and photo-crosslinking, which are then bottom-up assembled via dynamic crosslinking between dopamine-modified hyaluronic acid and phenylboronic acid groups on microgel surface. Results reveal that the microgel assembly can avoid the cell endocytosis of nanoparticles, ensure the high BMSC viability during the regular cell culture, cryopreservation and injection process, promote the chondrogenic differentiation of BMSCs. In addition, animal expriment proves the newborn cartilages present the typical characteristics of articular cartilage. In brief, this microgel assembly not only offers convenience for clinical use (injectability, tissue adhesion) but also provides good microenvironments for chondrogenesis (controlled drug release, interconnected micropores), indicative of its promising application for cartilage repair and regeneration.
由于缺乏血管、神经和淋巴，关节软骨缺损难以自我修复。尽管已有几种软骨组织工程产品获得临床批准，但仍存在一些问题，如手术切口大、与宿主组织的黏附力弱以及自体软骨细胞来源有限。本文报道了一种新型的具有优异微孔性、可注射性、组织黏附性和持续释放卡托辛（KGN）的动态纳米复合微凝胶组装体。具体来说，通过纳米乳化法合成载有 KGN 的环糊精纳米颗粒，并通过基于液滴的微流控技术和光交联将其掺入骨髓间充质干细胞（BMSCs）负载的微凝胶中，然后通过多巴胺修饰的透明质酸和苯硼酸基团之间的动态交联自下而上组装。结果表明，微凝胶组装体可以避免纳米颗粒的细胞内吞作用，确保常规细胞培养、冷冻保存和注射过程中高 BMSC 活力，促进 BMSCs 的软骨分化。此外，动物实验证明新生软骨具有关节软骨的典型特征。总之，这种微凝胶组装体不仅为临床应用（可注射性、组织黏附性）提供了便利，而且为软骨生成（控释药物、互连通孔）提供了良好的微环境，表明其在软骨修复和再生方面具有广阔的应用前景。
