Chitosan/poly (β-amino ester) hydrogel by controlled release of Centella Asiatica promoted wound healing through improved collagen expression and antibacterial and anti-inflammatory properties

Abstract

Burn wound healing presents several challenges, including impaired collagen synthesis, delayed wound closure, and disrupted inflammatory responses. This study investigates the potential of a novel UV-crosslinked hydrogel made of chitosan (CS)/poly(β-amino ester) (PβAE) and Centella Asiatica extract (CA) for second-degree burn wound treatment. Among various formulations, a monomer ratio of 1.5:1 and 5 wt% 2,2-dimethoxy-2-phenyl-acetophenone DMPA crosslinker concentration were found optimal. The hydrogel achieved a ~74% controlled release of CA over 72 h and showed significant enhancement in fibroblast viability (123.66 ± 9% at 5 days). Scratch assay demonstrated a ~99.5% wound closure within 24 h. Collagen type I expression was increased by ~1.7-fold compared with the control. Additionally, the hydrogel exhibited remarkable anti-inflammatory properties, effectively modulating the inflammatory response. It significantly reduced pro-inflammatory markers such as IL-6 and TNF-α while simultaneously enhancing the levels of anti-inflammatory cytokines, including IL-10 and TGF-β. This dual action not only mitigates inflammation but also fosters a regenerative environment, further supporting the healing process and promoting tissue recovery. The hydrogel exhibited antibacterial properties with inhibition zones of ~19.1 mm for E. coli and ~12.4 mm for S. aureus. These results suggest that this biocompatible, biodegradable hydrogel is a promising therapeutic candidate for second-degree burn wounds. Highlights: Developed a UV-crosslinked chitosan/PβAE hydrogel with Centella for burns. Optimized hydrogel releases ~74% Centella extract over 72 h. Boosts fibroblast viability, migration, and collagen I expression 1.7x. Reduces inflammation by modulating IL-6, TNF-α, IL-10, and TGF-β. Strong antibacterial action against E. coli and S. aureus.