Biphasic Scaffolds Functionalized with Piezoelectric Nanozymes for Osteochondral Defect Regeneration.

Abstract

Osteochondral defects remain clinically refractory due to the limited intrinsic repair capacity of avascular cartilage, inflammation, and reactive oxygen species (ROS). Herein, we develop an integrated biphasic osteochondral scaffold that couples mechanoelectrical stimulation with redox microenvironment regulation. CeMOF@BTO is fabricated by encapsulating barium titanate (BTO) within a cerium-based metal-organic framework (CeMOF), aiming to preserve piezoelectric responsiveness while providing catalytic ROS scavenging via the reversible Ce³⁺/Ce⁴⁺ redox cycle. This nanozyme is incorporated into GelMA/Alginate hydrogel to form the cartilage layer, whereas a GelMA/Alginate/β-TCP composite is extrusion-printed as the subchondral bone layer. Under ultrasound stimulation in vitro, the cartilage layer significantly boosts BMSC chondrogenesis; meanwhile, the β-TCP bone layer supports osteogenic differentiation. The biphasic scaffold achieves superior defect filling, hyaline-like cartilage regeneration, and osteochondral interface reconstruction in vivo. In general, this biphasic scaffold that synergizes piezoelectrically mediated bioelectrical cues and ROS modulation offers a promising strategy for achieving durable osteochondral regeneration.