Bioactive Bilayer Amniotic Membrane–Polycarbonate Urethane/Silk Fibroin Scaffold for Local Anti‐Inflammatory Therapy and Corneal Regeneration

ABSTRACT Corneal epithelial injuries require temporary matrices that combine structural support, ocular‐surface compatibility, and local anti‐inflammatory activity. We developed an ultrathin bilayer scaffold comprising decellularized human amniotic membrane (AM) coated with a polycarbonate urethane–silk fibroin emulsion layer (EM) containing 6% betamethasone dipropionate (BD). The construct was evaluated by morphological, spectroscopic, mechanical, qualitative optical, degradation, cytocompatibility, and rabbit corneal injury assessments. Cross‐sectional SEM confirmed integration of the two layers, and incorporation of the EM layer increased tensile strength, elongation at break, and Young's modulus relative to AM alone. In PBS, AM lost more than 60% of its initial dry mass over 25 days, whereas AM/EM and AM/EM + BD showed minimal mass loss. L929 fibroblast cells adhered to the scaffolds and maintained high metabolic activity for up to 7 days. In an ethanol‐assisted epithelial debridement model, AM/EM + BD treatment improved corneal clarity, epithelial organization, and stromal collagen architecture at day 21 and was associated with reduced TNF‐α, TGF‐β1, VEGF, and COL1 expression and increased IL‐10 and MMP9 expression. These findings support the AM/EM + BD scaffold as a mechanically reinforced, cytocompatible platform for local anti‐inflammatory corneal repair. In vitro release studies showed an initial burst followed by prolonged release, with approximately 60% of BD released at 24 h and a plateau of ~70%–72% reached by 96–192 h.