Intensified Stiffness and Photodynamic Provocation in a Collagen-Based Composite Hydrogel Drive Chondrogenesis
Intensified Stiffness and Photodynamic Provocation in a Collagen-Based Composite Hydrogel Drive Chondrogenesis
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胶原基复合水凝胶驱动软骨形成的增强刚度和光动力激发
DOI：
10.1002/advs.201900099
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发表时间：
2019
期刊：
影响因子：
15.1
通讯作者：
Zhao Jinmin
中科院分区：
文献类型：
--
作者：
Zheng Li;Liu Sijia;Cheng Xiaojing;Qin Zainen;Lu Zhenhui;Zhang Kun;Zhao Jinmin
骨髓间充质干细胞(BMSCs)向软骨方向定向分化是目前软骨修复的主要方法，但定向分化倾向差，分化效率低。为了克服这两个障碍，构建了一种由胶原水凝胶作为支架支撑的可注射复合水凝胶，以容纳骨髓间充质干细胞和硒化镉(CdSe)量子点。CdSe量子点的引入通过天然交联剂(即染料木素)的相互交联会显著增强胶原水凝胶的硬度，同时触发光动力激发(PDP)产生活性氧物种(ROS)。实验结果表明，僵硬增强和ROS产生增加可以协同促进BMSCs的增殖，诱导软骨特异性基因表达，增加糖胺聚糖的分泌。结果表明，该方法可促进骨髓间充质干细胞定向分化为软骨形成，促进软骨再生，其途径分别是通过激活转化生长因子-β/sMAD和mTOR信号转导通路。因此，这种基于增加硬度和PDP介导的ROS产生的协同策略为开发适用于软骨修复的替代材料提供了一种普遍和有指导意义的方法。
Directed differentiation of bone‐marrow‐derived stem cells (BMSCs) toward chondrogenesis has served as a predominant method for cartilage repair but suffers from poor oriented differentiation tendency and low differentiation efficiency. To overcome these two obstacles, an injectable composite hydrogel that consists of collagen hydrogels serving as the scaffold support to accommodate BMSCs and cadmium selenide (CdSe) quantum dots (QDs) is constructed. The introduction of CdSe QDs considerably strengthens the stiffness of the collagen hydrogels via mutual crosslinking using a natural crosslinker (i.e., genipin), which simultaneously triggers photodynamic provocation (PDP) to produce reactive oxygen species (ROS). Experimental results demonstrate that the intensified stiffness and augmented ROS production can synergistically promote the proliferation of BMSCs, induce cartilage‐specific gene expression and increase secretion of glycosaminoglycan. As a result, this approach can facilitate the directed differentiation of BMSCs toward chondrogenesis and accelerate cartilage regeneration in cartilage defect repair, which routes through activation of the TGF‐β/SMAD and mTOR signaling pathways, respectively. Thus, this synergistic strategy based on increased stiffness and PDP‐mediated ROS production provides a general and instructive approach for developing alternative materials applicable for cartilage repair.