Bioinspired ECM-specific microenvironment scaffold: A multi-biomimetic strategy spatially guides osteochondral regeneration

Clinically, cartilage injuries often involve simultaneous damage to the subchondral bone. However, the extracellular matrix (ECM) microenvironment of cartilage and subchondral bone varies greatly, making it a challenge to design scaffolds that match the osteochondral repair microenvironment. Herein, we proposed a bilayer scaffold with dual-tissue-specific ECM microenvironments for spatially guiding osteochondral regeneration via a multiple biomimetic strategy. Specifically, bone ECM-like chitosan/chitin whisker (CHW) liquid crystal (LC) hydrogel radial microchannels and deferoxamine-loaded polyethylene glycol diacrylate (PEGDA)/CHW LC hydrogel central longitudinal canal were constructed in 3D printed poly( l -lactide) scaffold as the osteogenic layer, while a cartilage ECM-like viscoelastic PEGDA/CHW LC hydrogel encapsulated with baicalin was designed as the chondrogenic layer. Results indicate that bone ECM-like LC state and microchannels, in conjunction with deferoxamine, can efficiently synergistically boost osteogenic differentiation and vascularization. Furthermore, LC state and viscoelastic hydrogel remodels the stem cell microenvironment and promote the chondrogenic differentiation of stem cells with baicalin. This multiple biomimetic scaffold exhibits satisfactory regenerative ability around rabbit osteochondral defect, facilitating simultaneous regeneration of cartilage and vascularized subchondral bone. This multiple biomimetic strategy achieves highly simulated construction of dual-tissue-specific ECM microenvironments, providing new insights for guiding osteochondral regeneration.