Fermented Plant Extract-Loaded Collagen Scaffolds: Bioactive Hydrogels for Enhanced Wound Repair and Immune Modulation

Fermented extracts of <i>Flourensia cernua</i> (<i>F. cernua</i>), enriched with bioactive polyphenols such as caffeic acid, apigenin, myricetin, and quercetin, exhibit strong potential to promote tissue regeneration. However, controlled delivery systems are required to enhance their bioavailability and therapeutic efficacy. In this study, <i>F. cernua</i> extracts (7-21 wt.%) were encapsulated in collagen hydrogels to develop bioactive matrices with sustained release properties. The hydrogel with 14 wt.% enabled sustained extract release from day 5 under physiological conditions and skin-mimicking pH (4.5). Increasing the extract concentration led to enhanced hydration behavior (>1400%) and crosslinking density (>45%), contributing to faster gelation. SEM analysis revealed fibrillar morphologies with amorphous globular domains whose prevalence increased with extract content and conferred improved thermal stability. Mechanical analysis indicated a decrease in matrix stiffness due to repulsive interactions between the extract components and the polymer network. Biodegradation studies showed slow hydrolytic and enzymatic degradation at skin pH in hydrogels containing 7 wt.% extract. All hydrogels demonstrated hemocompatibility, with no erythrocyte lysis. Moreover, hydrogels with 14 wt.% extract significantly enhanced the metabolic activity and proliferation of monocytes and fibroblasts, while 7 wt.% extract reduced TNF-α secretion, indicating anti-inflammatory potential. In vitro wound closure assays revealed 90% contraction within 10 days in fibroblast cultures exposed to 14 wt.% extract-loaded hydrogels. These results support the use of <i>F. cernua</i>-enriched collagen hydrogels as multifunctional scaffolds for wound healing and tissue regeneration.