Department of Orthopaedics, The First School of Clinical Medicine of Lanzhou University, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
J Biomed Nanotechnol. 2022 Jan 1;18(1):61-76. doi: 10.1166/jbn.2022.3239.
Kartogenin (KGN) can effectively promote the differentiation of adipose derived stem cells (ADSCs) into chondrocytes. With the help of three-dimensional slow-release technology, nano-microspheres are generated and used for cartilage repair. First, KGN solution was prepared, which was dissolved in distilled water, and NaOH solution, HEPES buffer, sodium chloride particles, and hydroxyapatite (HA) solution were added to prepare KGN-HA gel solution containing KGN. ADSCs were isolated from the posterior iliac of four-week-old New Zealand rabbits. After 0.5 mL of rabbit second-generation ADSCs suspension was taken, 2 mL KGN-HA gel solution was added, and they were mixed well to obtain ADSCs/KGN-HA gel. After drying treatment, ADSCs/KGN-HA nanospheres were precipitated. In the experiment, the minimum inhibitory concentration (MIC) of (MIC) > 2 μg/mL in each group of KGN-HA gel solution was reached within 30 days. Group K3 had the highest KGN encapsulation rate and the largest cumulative release. The biological activity of ADSCs was good in the ADSCs/KGN-HA nanoparticle solution. After two weeks of incubation, the nanospheres were positive for type II collagen staining/toluidine blue staining, that was, chondrocyte phenotype. The rabbit knee articular cartilage defect model was established. The defect part was filled with ADSCs/KGN-HA gel, which was similar in color to the surrounding tissues. The two sides of the tissue section and the surrounding cartilage tissue healed well, and no carrier material remained. Moreover, the cells were round, with cartilage lacuna formed around them, and after the simple periosteum was covered and repaired, the surface was sunken. The cell structure changed, and the healing with the surroundings was poor. In summary, under the slow release of KGN, ADSCs/KGN-HA nanospheres made ADSCs maintain a good biological form, which grew and proliferated normally. The ADSCs/KGN-HA nanoparticles cultured had a good repair effect on the animal model of articular cartilage defects.
Kartogenin (KGN) 可有效促进脂肪来源干细胞 (ADSCs) 向软骨细胞分化。借助三维缓释技术，生成纳米微球，并用于软骨修复。首先制备 KGN 溶液，将其溶解在蒸馏水中，加入 NaOH 溶液、HEPES 缓冲液、氯化钠颗粒和羟基磷灰石（HA）溶液，制备含有 KGN 的 KGN-HA 凝胶溶液。从 4 周龄新西兰兔的后髂取出 ADSCs，取 0.5mL 兔第二代 ADSCs 悬液，加入 2mL KGN-HA 凝胶溶液，混合均匀，得到 ADSCs/KGN-HA 凝胶。经干燥处理后，沉淀 ADSCs/KGN-HA 纳米球。实验中，各组 KGN-HA 凝胶溶液中（MIC）>2μg/mL 的最小抑菌浓度（MIC）在 30 天内达到。K3 组 KGN 包封率最高，累积释放量最大。ADSCs/KGN-HA 纳米颗粒溶液中 ADSCs 生物活性良好。孵育两周后，纳米球 II 型胶原染色/甲苯胺蓝染色阳性，即软骨细胞表型。建立兔膝关节软骨缺损模型，用 ADSCs/KGN-HA 凝胶填充缺损部位，颜色与周围组织相似。组织切片两侧及周围软骨组织愈合良好，无载体材料残留。而且细胞呈圆形，周围形成软骨陷窝，简单骨膜覆盖修复后，表面凹陷。细胞结构发生改变，与周围组织愈合不良。综上所述，在 KGN 的缓慢释放下，ADSCs/KGN-HA 纳米球使 ADSCs 保持良好的生物学形态，正常生长增殖。培养的 ADSCs/KGN-HA 纳米球对关节软骨缺损动物模型具有良好的修复作用。
