Journal
ADVANCED SCIENCE
Volume 6, Issue 16, Pages -Publisher
WILEY
DOI: 10.1002/advs.201900099
Keywords
cartilage repair; chondrogenesis; photodynamic provocation; reactive oxygen species; stiffness
Categories
Funding
- National Key Research and Development Program of China [2018YFC1105903]
- National Natural Science Foundation of China [81771836, 81760326, 81860390]
- Fostering Project of Shanghai Municipal Commission of Health and Family Planning for Excellent Young Medical Scholars [2018YQ31]
- Shanghai Science and Technology Committee Rising-Star Program [19QA1406800]
- Opening Project of Guangxi Key Laboratory of Bio-targeting Theranostics [GXSWBX201801]
- Opening Project of State Key Laboratory of High Performance Ceramics and Superfine Microstructure [SKL201811SIC]
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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-beta/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.
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