Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China.
State Key Laboratory of Molecular Engineering of Polymers & Department of Macromolecular Science, Fudan University, Shanghai 200433, China.
J Mater Chem B. 2020 Oct 7;8(38):8884-8893. doi: 10.1039/d0tb01686a.
Cartilage injury is very common and results in considerable pain and osteoarthritis. Owing to its low self-renewal capability, cartilage regeneration is still a great challenge for clinicians. Stem cell therapy has been treated as the most promising treatment for cartilage regeneration in recent decades. However, increasing concerns about the potential biosafety of stem cell products such as immune rejection and neoplastic transformation restrict their further application in clinic. Herein, biomimetic stem cell membrane-disguised nanovehicles without biosafety risks are designed and prepared for cartilage regeneration. In this study, based on the disguise of the natural bone marrow mesenchymal stem cell (BMSC) membrane, Kartogenin (KGN) as a drug for cartilage regeneration was encapsulated into Fe3O4 nanoparticles as the core of biomimetic stem cell nanovehicles. In the core-shell structure of biomimetic stem cell nanovehicles, the fabricated KGN-loaded BMSC membrane-disguised Fe3O4 nanoparticles (KGN-MNPs) showed a stable hybrid structure with a uniform size and morphology in the physiological environments. Moreover, the prepared KGN-MNPs exhibited excellent biocompatibility when disguised with the natural membrane of BMSCs and good biosafety by eliminating the nuclei of BMSCs. In a cartilage defect rat model, compared with pure KGN, the intra-articularly injected KGN-MNPs were capable of regenerating an integrated organized structure with a layer of hyaline-like cartilage in a shorter time due to the retained natural activities of the BMSC membrane. In a word, KGN-MNPs as one kind of our designed biomimetic stem cell nanovehicles enable rapid and high quality cartilage regeneration, and provide a novel and standardized strategy for stem cell therapy in the future.
软骨损伤非常常见，会导致严重的疼痛和骨关节炎。由于其自我更新能力低，软骨再生仍然是临床医生面临的巨大挑战。干细胞治疗被认为是近几十年来软骨再生最有前途的治疗方法。然而，人们越来越关注干细胞产品（如免疫排斥和肿瘤转化）的潜在生物安全性，这限制了它们在临床上的进一步应用。在此，设计并制备了具有生物安全性风险的仿生干细胞膜伪装纳米载体，用于软骨再生。在这项研究中，基于天然骨髓间充质干细胞（BMSC）膜的伪装，将软骨再生药物 Kartogenin（KGN）包封到作为仿生干细胞纳米载体核心的 Fe3O4 纳米颗粒中。在仿生干细胞纳米载体的核壳结构中，所制备的负载 KGN 的 BMSC 膜伪装的 Fe3O4 纳米颗粒（KGN-MNPs）在生理环境中表现出稳定的混合结构，具有均匀的尺寸和形态。此外，当用 BMSCs 的天然膜伪装时，所制备的 KGN-MNPs 表现出优异的生物相容性，并通过消除 BMSCs 的细胞核表现出良好的生物安全性。在软骨缺损大鼠模型中，与纯 KGN 相比，由于保留了 BMSC 膜的天然活性，关节内注射的 KGN-MNPs 能够在更短的时间内再生出具有一层透明软骨样结构的完整有序的组织。总之，KGN-MNPs 作为我们设计的一种仿生干细胞纳米载体，能够快速、高质量地再生软骨，并为未来的干细胞治疗提供一种新颖、标准化的策略。
