Novel hydrogel sealant promotes intestinal fistula healing through contraction-mediated re-epithelialisation of IEC

Author(s):
Ze Li; Jinjian Huang; Xiuwen Wu; Jianan Ren

Background:

Intestinal fistulas are intractable clinical problems, and promoting self-healing and avoiding laparotomy is the best therapeutic strategy, but traditional passive therapeutic measures such as irrigation and drainage have limited efficacy in promoting healing of intestinal fistulas. Mechanical force is a key regulator of tissue repair.

Hypothesis:

Hydrogel sealant constricts fistulae and promotes intestinal fistula healing through shear stress-mediated YAP activation.

Methods:

In this study, the results of RNA-seq, histopathologic staining, and Western Blot assay of clinical intestinal fistula tissues were used to guide the design of a hydrogel blocking agent. A novel injectable temperature-sensitive mechanically active hydrogel sealant was developed. The therapeutic efficacy and mechanism of action were evaluated by in vivo experiments.

Results:

The sealant was able to rapidly solidify and adhere to the intestinal fistula and actively contract the fistula at body temperature to reduce the defect area. Meanwhile, animal experiments showed that the shear stress generated by the hydrogel accelerated the re-epithelialisation of intestinal epithelial cells (IECs) and promoted intestinal fistula healing. In addition, RNA-seq revealed that YAP is a key signaling molecule for the proliferative activity of IEC.

Conclusions:

Our design provides a novel strategy to promote intestinal fistula healing and shows potential clinical applications.