Adipose-derived mesenchymal stem cell-loaded β-chitin nanofiber hydrogel promote wound healing in rats
Ying Liu, Yunen Liu, Mi Wu, Rufei Zou, Shun Mao, Peifang Cong, Mingxiao Hou, Hongxu Jin, Yan Zhao, Yongli Bao
Abstract
Because of stem cells are limited by the low efficiency of their cell homing and survival in vivo, cell delivery systems and scaffolds have attracted a great deal of attention for stem cells' successful clinical practice. β-chitin nanofibers (β-ChNF) were prepared from squid pens in this study. Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy proved that β-ChNFs with the diameter of 5 to 10 nm were prepared. β-ChNF dispersion became gelled upon the addition of cell culture medium. Cell culture experiments showed that β-ChNFs exhibited negligible cytotoxicity towards ADSCs and L929 cells, and it was found that more exosomes were secreted by the globular ADSCs grown in the β-ChNF hydrogel. The vivo experiments of rats showed that the ADSCs-loaded β-ChNF hydrogel could directly cover the wound surface and significantly accelerate the wound healing and promote the generation of epithelization, granulation tissue and collagen. In addition, the ADSCs-loaded β-ChNF hydrogel clearly regulated the expressions of VEGFR, α-SMA, collagen I and collagen III. Finally, we showed that ADSCs-loaded β-ChNF hydrogel activated the TGFβ/smad signaling. The neutralization of TGFβ markedly reduced Smad phosphorylation and the expressions of TIMP1, VEGFR and α-SMA. Taken together, these findings suggest that ADSCs-loaded β-ChNF hydrogel promises for treating wounds that are challenge to heal via conventional methods. Graphical abstract.