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Chitosan-glycerophosphate thermosensitive hydrogel inhibits breast implant-associated capsular contracture by
Wenwen Zhu1, Yuan Tian, Xinyue Wang
1Plastic Surgery and Cosmetology Center, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
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.
