Department of Spine Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.
Center for Orthopaedic Science and Translational Medicine, Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Free Radic Biol Med. 2023 Aug 1;204:128-150. doi: 10.1016/j.freeradbiomed.2023.04.018. Epub 2023 May 4.
Intervertebral disc (IVD) degeneration (IDD) and the consequent low back pain present a major medical challenge. Stem cell-based tissue engineering is promising for the treatment of IDD. However, stem cell-based treatment is severely impaired by the increased generation of reactive oxygen species (ROS) in degenerative disc, which can lead to a high level of cell dysfunction and even death. In this study, a kartogenin (KGN)@PLGA-GelMA/PRP composite hydrogel was designed and used as a carrier of ADSCs-based therapies in disc repair. Injectable composite hydrogel act as a carrier for controlled release of KGN and deliver ADSCs to the degenerative disc. The released KGN can stimulate the differentiation of ADSCs into a nucleus pulposus (NP) -like phenotype and boost antioxidant capacity of ADSCs via activating Nrf2/TXNIP/NLRP3 axis. Furthermore, the composite hydrogel combined with ADSCs attenuated the in vivo degeneration of rat IVDs, maintained IVD tissue integrity and accelerated the synthesis of NP-like extracellular matrix. Therefore, the KGN@PLGA-GelMA/PRP composite hydrogel is a promising strategy for stem cell-based therapies of IDD.
椎间盘（IVD）退变（IDD）和随之而来的下腰痛是一个主要的医学挑战。基于干细胞的组织工程对于治疗 IDD 很有前景。然而，由于退变椎间盘内活性氧（ROS）的产生增加，基于干细胞的治疗受到严重阻碍，这可能导致高水平的细胞功能障碍甚至死亡。在这项研究中，设计了一种卡托辛（KGN）@PLGA-GelMA/PRP 复合水凝胶，用作椎间盘修复中基于 ADSC 的治疗的载体。可注射的复合水凝胶作为 KGN 的控制释放载体，并将 ADSC 递送到退变的椎间盘。释放的 KGN 可以通过激活 Nrf2/TXNIP/NLRP3 轴，刺激 ADSC 分化为类髓核（NP）表型，并增强 ADSC 的抗氧化能力。此外，复合水凝胶与 ADSC 联合减轻了大鼠 IVD 的体内退变，保持了 IVD 组织的完整性，并加速了 NP 样细胞外基质的合成。因此，KGN@PLGA-GelMA/PRP 复合水凝胶是基于干细胞治疗 IDD 的一种有前途的策略。
