A Coaxial Bioprinted Hydrogel With Semipermeable Sheath and Pro‐Chondrogenic Core for Articular Cartilage Repair

Stem cell‐laden hydrogels represent a promising strategy for the functional repair of articular cartilage defects. However, the pathological joint microenvironment is often characterized by persistently elevated levels of pro‐inflammatory cytokines, which severely compromise transplanted cell survival and impair their chondrogenic differentiation potential. Inspired by the hierarchical mechanical gradient of native cartilage, we developed a sheath‐core biomimetic hydrogel (SC GAE ) via embedded coaxial bioprinting, featuring a robust poly(ethylene glycol)‐alginate (PA) sheath that spatially integrates mechanical support and immunoprotection around a soft, bioactive gelatin methacryloyl‐alginate‐decellularized extracellular matrix (GAE) core. The dense PA sheath provides immediate mechanical support and functions as a size‐selective diffusion barrier, permitting nutrient and oxygen permeation while effectively blocking inflammatory cytokines (>40 kDa). This protective niche enables the pericellular matrix‐mimicking GAE core to maintain stem cell viability >89% under pro‐inflammatory conditions and support robust chondrogenic differentiation. In a rabbit osteochondral defect model, bone marrow stromal cell‐laden SC GAE constructs promoted substantial cartilage repair, achieving defect filling, host integration, and regeneration of glycosaminoglycan‐rich hyaline‐like cartilage. This sheath‐core architecture design spatially integrates structural, mechanical, and immunoprotection functions, presenting a promising platform for the regeneration of load‐bearing articular cartilage.