Origami‐Folded PLLA/MXene Scaffold Promotes Cartilage Regeneration via Synergistic Piezoelectric Chondrogenesis and Photothermal Anti‑Angiogenesis

ABSTRACT Conventional piezoelectric scaffolds demonstrate promising prospects in cartilage regeneration by promoting chondrogenic differentiation via electrical stimulation. However, excessive subchondral angiogenesis induced by electrical cues can damage neocartilage and accelerate cartilage degradation, presenting a major obstacle to cartilage repair. Herein, we develop an origami‐inspired PLLA (poly Llactic acid)/MXene (two‐dimensional transition metal carbide) composite scaffold integrating dual regulatory mechanisms. The electrospun PLLA/MXene nanofibers are assembled into three‐dimensional origami structures through template compression. MXene incorporation and origami architecture synergistically enhance piezoelectric output, achieving ∼3.8 V voltage and ∼12 nA current in the scaffolds under cyclic compression, approximately 2‐fold higher than pure PLLA scaffolds. The scaffold maintains stable piezoelectric performance under physiological conditions and throughout degradation. Moreover, MXene nanosheets confer rapid and efficient photothermal responsiveness, elevating temperature to mild hyperthermia under near‐infrared irradiation to suppress angiogenesis. In vitro studies demonstrate that synergistic piezoelectric‐photothermal stimulation promotes chondrogenesis through TRPV4/PI3K/Akt pathway while suppressing tube formation via VEGF/FAK pathway. In a rat osteochondral defect model, the dual‐functional scaffold achieves superior cartilage regeneration with enhanced matrix deposition, reduces subchondral vascularization, and preserves the hypoxic niche. This origami‐structured piezoelectric‐photothermal biomaterial offers a promising strategy for orchestrated cartilage repair through synergistic biophysical cues.