Bi-phasic integrated silk fibroin/polycaprolactone scaffolds for osteochondral regeneration inspired by the native joint tissue and interface

Osteochondral scaffolds designed with bi-phasic and multi-phasic have typically struggled with post-implantation delamination. To address this issue, we developed a novel integrated scaffold with natural and continuous interface and heterogeneous bilayer structure. Through layer-by-layer wet electrospinning, two-dimensional (2D) bi-layer integrated membranes of silk fibroin (SF) and polycaprolactone (PCL) were fabricated. These membranes were then transformed into three-dimensional (3D) scaffolds using a CO₂ gas foaming technique, followed by gelatin coating on the osteogenic layer to afford final bi-phasic porous scaffolds. <i>In vitro</i> studies indicated that the 3D scaffolds better-maintained cell phenotypes than conventional 2D electrospun films. Additionally, the 3D scaffolds showed superior cartilage repair and osteoinductivity potential, with increased subchondral bone volume and reduced defect area in rat osteochondral defects models at 12 weeks. Taken together, these gas-foamed scaffolds were a promising candidate for osteochondral regeneration.