Department of Orthopedic, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
J Nanobiotechnology. 2023 Nov 28;21(1):453. doi: 10.1186/s12951-023-02226-1.
Cell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive.
In this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg to histidine-functionalized hyaluronic acid (HA-His-Mg) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg, GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model.
The GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPCs effectively alleviated nucleus pulposus degeneration and promoted its regeneration in the rat IVDD model.
In conclusion, we constructed a keep charging system with a double-network hydrogel microsphere as a framework and Mg as a cell activity enhancer, which effectively maintains NPCs active to fight against the harsh microenvironment in the degenerative intervertebral disc. The GHHM@NPCs system provides a promising approach for IVDD management.
细胞移植已被证明是组织再生的一种很有前途的方法。然而，在退化组织中，活性氧（ROS）的积累和炎症条件会形成恶劣的微环境，使移植细胞难以存活。
在这项研究中，我们构建了一种持续充电水凝胶微球系统，使细胞能够在退化的椎间盘内积极增殖和发挥功能。具体来说，我们通过配位反应将镁与组氨酸功能化透明质酸（HA-His-Mg）结合，然后通过微流控方法与 GelMA 交联构建双网络水凝胶微球（GelMA/HA-His-Mg，GHHM）。体外，将负载有髓核细胞的 GHHM（GHHM@NPCs）进一步测试其促进 NPCs 增殖和抗炎的能力。体内，通过大鼠椎间盘针刺模型评估 GHHM@NPCs 促进 NP 组织再生和挽救椎间盘退变（IVDD）的能力。
GHHM 显著增强了 NPCs 的黏附和增殖能力，为 NPCs 的生长提供了理想的平台。负载的 NPCs 被 GHHM 微球中的镁充电，保持在活跃状态，有效支持负载的 NPCs 对抗 ROS 诱导的炎症和衰老。此外，我们观察到 GHHM@NPCs 有效缓解了椎间盘的退变，促进了其在大鼠 IVDD 模型中的再生。
总之，我们构建了一种以双网络水凝胶微球为框架、镁为细胞活性增强剂的持续充电系统，有效地维持了 NPCs 的活性，使其能够抵抗退化椎间盘恶劣的微环境。GHHM@NPCs 系统为 IVDD 的治疗提供了一种有前途的方法。
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