Silica meets flavonoid: zwitterionic silica-quercetin nanocarriers embedded in electrospun fibers for wound healing

Silica-based nanomaterials are widely applied in biomedicine; however, achieving stable bioactive functionalization and integrating multiple therapeutic functions within a single material remain important challenges. Herein, we report the fabrication of multifunctional zwitterion-grafted silica nanoparticles loaded with quercetin (Zw-SiNPs@Q) and their incorporation into electrospun poly(vinyl alcohol)/poly(acrylic acid) (PVA-PAA) nanofibers to create bioactive hybrid wound dressings. The distinctive feature of this approach is the use of Zw-grafted SiNPs as an intermediate nanoengineered interface for Q immobilization before their incorporation into the electrospun matrix, rather than directly blending the bioactive molecule with the polymer. Zwitterionic polymer chains were covalently grafted onto the surfaces of SiNPs via radical copolymerization, followed by Q functionalization. Structural and compositional analyses confirmed successful stepwise surface modification while preserving nanoparticle morphology. The resulting Zw-SiNPs@Q/PVA-PAA nanofibers exhibited sustained and concentration-dependent Q release over 72 h without a pronounced burst effect, highlighting the ability of the nanoengineered interface to serve as a reservoir for localized prolonged Q delivery. The hybrid nanofibers demonstrated strong antioxidant activity and concentration-dependent antibacterial effects against both E. coli and S. aureus, with complete bacterial inhibition observed in pre-annealed samples. The materials also exhibited excellent cytocompatibility, maintaining >80% viability in L929 fibroblasts. In an LPS-induced inflammatory model, Zw-SiNPs@Q3.2/PVA-PAA nanofibers significantly downregulated pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) while upregulating IL-10 and TGF-β, indicating a shift toward a pro-resolving microenvironment. Scratch wound-healing assays further revealed accelerated wound closure, with wound gaps reduced to ∼30% at 72 h compared to ∼60% in controls. By integrating a zwitterionic nanoengineered interface with sustained Q delivery, antioxidant activity, and immunomodulatory effects, this study yields a multifunctional nanofibrous platform that addresses biological processes relevant to wound healing. These findings establish Zw-SiNPs@Q/PVA-PAA nanofibers as a promising bioactive interface for advanced wound management and tissue repair applications.