Abstract
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.
Highlights
Directed differentiation of bone-marrow-derived stem cells (BMSCs) toward bone-marrow-derived stem cells (BMSCs) in scaffolds for enabling the lineage-spechondrogenesis has served as a predominant method for cartilage repair cific differentiation toward chondrogenesis but suffers from poor oriented differentiation tendency and low differentiahas attracted increasing interest.[2]
The dark green in CG and collagen– genipin–QDs (CGQ) gels is attributed to the successful crosslinking of genipin with cadmium selenide (CdSe) quantum dots (QDs) and collagen through reacting with amines, suggesting that genipin can serve as an indicator of crosslinking based on its color change
Much stronger characteristic peaks of selenium and cadmium elements in energy-dispersive spectrometry (EDS) analysis confirm the successful linkage of more CdSe QDs in CGQ hydrogels (Figures 2c) in comparison to C and CG hydrogels (Figure S1b, Supporting Information)
Summary
After crosslinking with genipin, the pore sizes of CG and CGQ hydrogels, which can be measured according to scanning electron microscopy (SEM) images,[19] decreases from ≈100 to ≈50 μm (Figure 2d) Their Fourier transform infrared spectra (FTIR) further demonstrate the successful crosslinking of collagen with genipin and QDs in CGQ (Figure 2e). In UV–vis spectra, a characteristic absorbance peak at 595 nm emerges in CG and CGQ gels due to the genipin crosslinking-induced color change after 24 h incubation (Figure S3, Supporting Information). To further verify this result, the peak value at 630 nm in their photoluminescence spectra was recorded using a 595 nm laser as the excitation source.
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