Yang Shan-Wei, Chen Yong-Ji, Chen Ching-Jung, Liu Jen-Tsai, Yang Chin-Yi, Tsai Jen-Hao, Lu Huai-En, Chen San-Yuan, Chang Shwu-Jen
Department of Orthopedics, Kaohsiung Veterans General Hospital, Kaohsiung City 813414, Taiwan.
Department of Biomedical Engineering, I-Shou University, Kaohsiung City 813414, Taiwan.
Polymers (Basel). 2022 Feb 19;14(4):809. doi: 10.3390/polym14040809.
Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair.
骨关节炎（OA）是一种全球范围内发生的关节软骨退变疾病，会对患者的身心健康产生不利影响，包括活动受限。OA的一个主要病理特征主要与OA关节中磨损以及分解代谢和促炎介质导致的关节软骨缺损有关。尽管细胞疗法迄今为止一直被视为OA的一种有前景的治疗方法，但由于植入细胞的流出，治疗效果未达预期。在此，我们旨在探索使用磁性两亲性明胶纳米载体（MAGNC）对软骨细胞进行磁化的修复效果，以提高细胞锚定效率和细胞向受损软骨表层区域的磁导向（MG）。体外实验结果表明，磁化软骨细胞可沿磁力线快速导向，形成细胞聚集。此外，MAGNC中明胶的精氨酸 - 甘氨酸 - 天冬氨酸（RGD）基序可整合细胞间相互作用，形成细胞堆叠。另外，MAGNC上调了Ⅱ型胶原蛋白（Col II）、聚集蛋白聚糖的基因表达，并下调了Ⅰ型胶原蛋白（Col I）的基因表达，以减少细胞去分化。在动物模型中，磁化软骨细胞可通过内部磁场与MAGNC之间的相互作用被引导至表层区域，形成细胞堆叠。体内结果显示，磁导向的磁化细胞组中N - 硫酸化糖胺聚糖（sGAG）和Col II的强度高于其他组。此外，植入8周后，在表层区域观察到OA软骨缺损的平滑闭合。该研究揭示了MAGNC在促进软骨细胞高密度堆叠至软骨表面以及保留植入软骨细胞的生物学功能以修复OA软骨方面具有巨大潜力。
