Identifying the Optimal Engineering Fabrication Strategy for Decellularized Cartilage Matrix‐Based Regeneration: Hierarchical Topology Superiority in Cartilage Regeneration

The integration of bioactive matrix components and precise spatial architectures represents a promising strategy for regenerating complex tissues like articular cartilage. While decellularized cartilage matrix (DCM) preserves essential regenerative cues, the optimal engineering fabrication strategy to translate its biochemical potential remains to be defined. In this study, we conducted a systematic technological screening by fabricating three distinct DCM‐based topological prototypes: randomized porous scaffolds (RPS) via traditional lyophilization, oriented porous scaffolds (OPS) via ice‐templating, and hierarchical porous scaffolds (HPS) via low‐temperature 3D printing. Our findings reveal that the HPS configuration, characterized by its multi‐scale hierarchical porosity, functions as a biophysical instructor that activates the FAK‐PI3K/AKT mechanotransduction axis. Unlike RPS and OPS, HPS uniquely reprograms the BMSC secretome into a robust paracrine factory, effectively balancing pathological homeostasis and shielding chondrogenesis from inflammatory degradation. This study establishes the hierarchical architecture as the superior engineering fabrication solution for DCM‐based regeneration, offering a new paradigm for instructive cartilage defect repair.