Local Sustained‐Release of Triamcinolone‐Acetonide‐Loaded Regenerated Silk Fibroin Formulations for the Inhibition of Scar Hyperplasia in Rabbit Ears

To investigate the safety, efficacy, and underlying mechanisms of triamcinolone-acetonide-loaded silk fibroin formulations in inhibiting scar hyperplasia in rabbit ears. This study employed molecular induction self-assembly and high-energy ball milling to prepare triamcinolone acetonide (Tr-A)-loaded sustained-release microspheres, RSF-Tr-A, using different inducers and concentrations of regenerated silk fibroin (RSF). Bio-safety was confirmed via CCK-8 and Live-Dead assays. The levels of growth factors and inflammatory cytokines were examined through RT-PCR. In a rabbit ear scar model, ultrasound Doppler assessed scar thickness and blood flow, a colorimeter recorded scar color changes, and Masson's trichrome staining evaluated collagen content and new collagen changes. CD31 immunohistochemistry determined vascular content in scarred skin. The RSF-Tr-A microsphere formulation was successfully prepared. In vitro tests showed good biosafety and significant inhibition of fibroblast proliferation and migration (p < 0.001). It also promoted apoptosis (p < 0.001) and reduced tube formation (p < 0.01 and p < 0.05). RT-PCR confirmed suppression of VEGF, EGF, bFGF, TGF-β1, IL-6, IL-1β, and TNF-α (p < 0.001). In a rabbit ear scar model, VSS and SEI scores were significantly lower (p < 0.05, p < 0.01, p < 0.001) and scar color difference was significantly different (p < 0.001) at 5 W post-treatment. Histological analyses showed milder inflammation and collagen hyperplasia inhibition (p < 0.05 and p < 0.01) and reduced new blood vessel formation. The RSF-Tr-A microsphere formulation demonstrates good bio-safety and can effectively suppress fibroblast proliferation, collagen synthesis, inflammatory responses, and neovascularization through sustained release, thereby inhibiting scar hypertrophy.