Chitosan-glycerophosphate thermosensitive hydrogel inhibits breast implant-associated capsular contracture by regulating the IRAK1-MAPK pathway.

BACKGROUND

Capsular contracture is a common complication following breast reconstruction or prosthetic implantation, characterized by excessive activation of fibroblasts and abnormal deposition of extracellular matrix (ECM). Chitosan-glycerophosphate thermosensitive hydrogel (C-GP gel) exhibits excellent injectability and biocompatibility; however, its direct impact and underlying mechanism on capsular contracture are still not well understood. This study aims to investigate the mechanism by which C-GP gel inhibits capsular contracture, providing insights for the development of novel therapeutic strategies.

METHODS

After preparing C-GP gel and verifying its in vivo biosafety, we established in vivo rabbit capsular contracture models and in vitro-cultured human skin fibroblasts (HSFs), and randomly divided both animal and cellular samples into control and C-GP gel treatment groups, with an extra osmotic pressure-matched control group applied to cellular experiments. The effects and the mechanisms were assessed via cell function assays, RNA sequencing, Western blotting analysis, immunohistochemistry, and histological examination.

RESULTS

Animal experiments showed that C-GP gel effectively reduced capsule thickness and collagen deposition and downregulated the expression of proteins related to the interleukin-1 receptor-associated kinase 1 (IRAK1)-mitogen-activated protein kinase (MAPK) pathway. In vitro, C-GP gel inhibited HSF proliferation and migration, promoted apoptosis, arrested the cell cycle at the S phase, and significantly downregulated IRAK1-MAPK pathway activity. Based on in vivo and in vitro results, the anti-capsular contracture capacity of chitosan hydrogel is attributed to its downregulatory effect on the IRAK1-MAPK signaling pathway.

CONCLUSION

Chitosan-glycerophosphate thermosensitive hydrogel inhibits capsular contracture and is associated with downregulation of the IRAK1-MAPK pathway, thus holding potential clinical application value.