BACKGROUND Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have been induced to chondrocytes with the help of some small molecules within 21-36 days. To speed up the differentiation of iPSCs, we supposed to utilize bioactive ceramics to assist chondrogenic-induction process. METHODS In this study, we applied ionic products (3.125~12.5 mg/mL) of the lithium-containing bioceramic (Li2Ca4Si4O13, L2C4S4) and individual Li+ (5.78~23.73 mg/L) in the direct chondrogenic differentiation of human iPSCs. RESULTS Compared to pure chondrogenic medium and extracts of tricalcium phosphate (TCP), the extracts of L2C4S4 at a certain concentration range (3.125~12.5 mg/mL) significantly enhanced chondrogenic proteins Type II Collagen (COL II)/Aggrecan/ SRY-Box 9 (SOX9) synthesis and reduced hypertrophic protein type X collagen (COL X)/matrix metallopeptidase 13 (MMP13) production in iPSCs-derived chondrocytes within 14 days, suggesting that these newly generated chondrocytes exhibited favorable chondrocytes characteristics and maintained a low-hypertrophy state. Further studies demonstrated that the individual Li+ ions at the concentration range of 5.78~23.73 mg/L also accelerated the chondrogenic differentiation of iPSCs, indicating that Li+ ions played a pivotal role in chondrogenic differentiation process. CONCLUSIONS These findings indicated that lithium-containing bioceramic with bioactive specific ionic components may be used for a promising platform for inducing iPSCs toward chondrogenic differentiation and cartilage regeneration.

中文翻译：

---

含锂的生物材料通过减少肥大促进诱导的多能干细胞的软骨分化。

背景技术诱导的多能干细胞（iPSC）显示出无限的多能可塑性和增殖能力，从而为组织再生医学提供了丰富的细胞来源。因此，诱导iPSC朝着特定的分化方向是一个重要的科学问题。传统上，已在21-36天内借助一些小分子将iPSC诱导为软骨细胞。为了加快iPSC的分化，我们应该利用生物活性陶瓷来辅助成软骨诱导过程。方法在本研究中，我们将含锂生物陶瓷（Li2Ca4Si4O13，L2C4S4）和单个Li +（5.78〜23.73 mg / L）的离子产物（3.125〜12.5 mg / mL）用于人iPSC的直接软骨分化。结果与纯软骨形成培养基和磷酸三钙（TCP）提取物相比，一定浓度范围（3.125〜12.5 mg / mL）的L2C4S4提取物显着增强了软骨生成蛋白II型胶原蛋白（COL II）/ Aggrecan / SRY-Box 9（SOX9）的合成，并减少了肥大性X型胶原蛋白（COL X） iPSCs来源的软骨细胞在14天内产生了/基质金属肽酶13（MMP13），这表明这些新生成的软骨细胞表现出有利的软骨细胞特性并保持了低肥大状态。进一步的研究表明，浓度范围为5.78〜23.73 mg / L的单个Li +离子也促进iPSCs的软骨形成分化，表明Li +离子在软骨分化过程中起着关键作用。