Feedback delivery of BMP 7 on the pathological oxidative stress via smart hyaluronic acid hydrogel potentiated the repairing of the gut epithelial integrity

Abstract

The intestinal barrier integrity was substantially collapsed when colitis flaring up, accompanying by the hallmark of pathological oxidative stress. Bone morphogenetic protein 7 (BMP 7), an endogenous growth factor in gut had the potential to repair the damaged mucosa. Herein, a smart hydrogel (HDP) had been developed by the boronate-ester crosslinked hyaluronic acid to deliver BMP 7. Hydrogel loading BMP 7 (HDP-BMP 7) presented the comparable mechanical strength with that of the naïve gut mucus. HDP-BMP 7 as artificial mucus could specifically adhere to the inflamed colonic mucosa of colitis mice. Importantly, it could apperceive reactive oxygen species at diseased colon to adapt its intrinsic network, enabling the feedback release of BMP 7 on the pathological oxidative stress. Moreover, in vivo animal experiments showed that the disease symptoms of colitis mice were alleviated by HDP-BMP 7. Importantly, both the mucus barrier and the epithelial barriers were obviously recovered by HDP-BMP 7 treatment, which substantially attenuated the immune-inflammation response of colitis mice. Besides, HDP-BMP 7 enriched the diversity of gut flora, increasing the relative abundance of Lactobacillus and decreasing the ratio of Firmicutes/Bacteroidetes. Its therapeutic mechanism was associated with activating TGF-β/Smad signals. Conclusively, this smart hydrogel might potentiate the repairing effect of growth factors on the gut epithelial integrity.