Scaffold providing spatial guidance enhances the healing of osteochondral defects and reduce adverse bone-cartilage crosstalk

Despite previous attempts using multiphasic scaffolds to organize cells and bioactive elements, osteochondral repair still faces challenges, such as thin cartilage layers and uneven bone-cartilage interfaces. These issues are likely exacerbated by detrimental biochemical interactions and the formation of new blood vessels within the osteochondral unit, impacting tissue repair quality. In this study, we devised a novel freeze-welding technique to create a unified porous scaffold. Chitosan was chosen as the primary material due to its structural and compositional similarity to glycosaminoglycans in the ECM. In particular, by meticulously adjusting freezing and solute conditions, we engineered the scaffold to have an axially aligned porous structure in the cartilage layer and a radially aligned porous structure in the subchondral layer (scaffold A/R), each designed to meet the unique repair needs of the respective tissues. This scaffold showed enhanced mechanical compressibility, shape retention, and interfacial bonding capabilities. The results demonstrated that this unique spatial scaffold structure offers significant advantages over purely axial scaffolds in guiding osteochondral regeneration. These advantages were evident in its ability to independently promote cartilage and bone growth, reduce undesirable bone-cartilage crosstalk, particularly in the context of vessel invasion in the cartilage layer, and optimize the remodeling of the osteochondral interface. This study offers valuable insights into the structural design patterns for osteochondral regeneration, highlighting the potential importance of structural scaffold design in guiding endogenous tissue remodeling during heterogeneous tissue regeneration.