One-step encoding of quasi-continuous compositional and structural gradients in melt electrowritten scaffolds for osteochondral regeneration.

Engineering osteochondral scaffolds with continuous gradients remains a central challenge in regenerative medicine. Here, we present a one-step melt electrowriting (MEW) strategy to encode quasi-continuous compositional and structural gradients in poly(ε-caprolactone) (PCL) scaffolds. By sequentially loading nanohydroxyapatite (nHA)-laden PCL melts, a predefined mineral gradient is preserved during printing, yielding a continuous decrease in nHA content across the scaffold thickness. This gradient intrinsically drives a concomitant reduction in fiber diameter, thereby recapitulating the native transition from subchondral bone to cartilage. A porous TGF-β1-loaded hydrogel coating is further introduced to provide spatially relevant chondrogenic cues without compromising pore interconnectivity. The resulting scaffolds exhibit graded composition, structure, and mechanical properties, enabling coordinated osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro and promoting integrated osteochondral repair in vivo. This work establishes a generalizable MEW-based platform for single-step gradient encoding and offers a biomimetic design strategy for complex tissue interfaces.