Adhesive hydrogel based on Konjac Glucomannan (KGM) loaded with siACTC1-exosomes for enhanced post-surgical keloid treatment.

Abstract

BACKGROUND: Keloids, dermal fibroproliferative disorders, frequently reemerge after surgical intervention, potentially due to skin tension, a factor often overlooked in treatment strategies. METHODS: In this study, we identified Alpha cardiac muscle 1 (ACTC1) as a key cytoskeletal target in the mechano-transduction of keloids through bioinformatic analysis and in vitro experiments. We developed an adhesive hydrogel based on lipoic acid-modified konjac glucomannan (KGM-LA), a natural polysaccharide, loaded with siACTC1. This hydrogel serves as a tension-free wound dressing to mitigate keloid proliferation. RESULTS: ACTC1 was significantly upregulated in keloid tissues and fibroblasts compared to normal controls. siACTC1 effectively reduced the proliferation, invasiveness, and levels of F-actin, α-SMA, and collagen I in keloid fibroblasts. The KGM-LA hydrogel demonstrated excellent adhesiveness, biocompatibility, injectability, and degradability, making it ideal for sustained siRNA release and tension reduction at wound sites. Notably, the siACTC1-loaded hydrogel significantly suppressed keloid growth in a mouse model by sustainably inhibiting ACTC1 and reducing mechanical tension. CONCLUSIONS: Our study demonstrates that the KGM-LA-based adhesive hydrogel loaded with siACTC1 effectively inhibits keloid growth post-surgery, highlighting its potential for future clinical applications in keloid treatment.