Phytochemical-loaded silk fibroin-chitosan nanocarriers for modulating collagen I/III expression via controlled bioorganic interactions.

This study aimed to obtain a bioorganic strategy for skin tissue regeneration by integrating phytochemical-loaded nanocarriers into a biomimetic scaffold system. Chelidonium majus root extract was first chemically characterized by GC-MS, which revealed high abundances of bioactive alkaloids (42.20%), triterpenes (23.05%), fatty acids (13.57%), flavonoids (3.01%), and other plant metabolites. The extract possessed a high total phenolic content (120.47 ± 1.83 mg GAE/g) and strong antioxidant activity (IC₅₀ = 24.05 μg/mL), suggesting potent free-radical scavenging capacity. The mentioned extract was encapsulated into silk fibroin-chitosan (SFCh) nanoparticles at varying blend ratios of 100:0 to 50:50, for controlled delivery. Based on the results, the SFCh20 (80:20) formulation demonstrated the highest encapsulation efficiency (86.05%) and structural homogeneity. In the following, the phytochemical-loaded nanoparticles were conjugated within a PVA-collagen scaffold, where intermolecular interactions modulated nanoparticle distribution, pore architecture, and extract release, which followed a quasi-Fickian diffusion mechanism and occurred at a slower rate compared to uncross-linked systems. Biologically, scaffolds conjugated with extract-loaded nanoparticles (S3) led to a significant increase in fibroblast adhesion, spreading, and proliferation compared to empty nanoparticle-conjugated scaffolds, as confirmed by SEM imaging and MTT assays. Moreover, sustained release of phytochemical agents promoted collagen type I and III expression at days 7 and 14, surpassing even TGF-β-treated controls. These findings demonstrate that the molecular interaction between plant-derived bioactives and polymeric nanocarriers can be used to regulate extracellular matrix formation, highlighting a bioorganic approach for the development of advanced wound-healing scaffolds.