Antibiofilm and wound healing effects of Triphala polyphenol-loaded silver nanoparticles hydrogel through regulation of MMP-9, inflammatory cytokines, and collagen deposition

Deviation in the normal wound healing process often results in the development of chronic wounds, frequently worsened by ongoing inflammation, bacterial presence, particularly biofilms. The aim of this study was to investigate the antibiofilm and wound healing potential of synergistic therapeutic effects of polyphenol-rich methanolic extract of triphala and silver nanoparticles and to study the underlying mechanisms. Triphala, an ayurvedic herbal preparation rich in polyphenols, exhibits antioxidant, anti-inflammatory, and matrix metalloproteinase (MMP) regulating properties. Various polyphenolic compounds such as gallic acid, ellagic acid, quercetin and β-sitosterol were identified and quantified in the triphala powder extract (TPE) using LC-MS/MS. TPE-loaded SNPs were synthesised and found to be small, spherical and stable. TPE-loaded SNPs exhibited greater biofilm inhibition against Staphylococcus aureus than Pseudomonas aeruginosa . TPE-loaded SNPs hydrogel was formulated and evaluated. In vivo wound healing studies in wistar rats demonstrated TPE-loaded SNPs gel significantly accelerated wound contraction and achieved complete wound closure with minimal scarring, outperforming plain SNPs, TPE alone, and a marketed formulation. Biochemical estimations revealed increased hydroxyproline content, indicating enhanced collagen deposition. The TPE-loaded SNPs group also showed significantly reduced levels of inflammatory markers (IL-6 and TNF-α) and lower oxidative stress (SOD levels) compared to control and other treatment groups, suggesting effective modulation of the inflammatory response. Furthermore, MMP-9 levels were estimated, providing insight into extracellular matrix remodeling. These findings highlight the promising antimicrobial, antibiofilm, and wound healing properties of TPE-loaded SNPs, suggesting their potential as an effective therapeutic strategy for wound management.