Highly biomimetic three-layer mineralized collagen scaffold featuring a wood-reinforced subchondral bone region for gradient chondrogenic-osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Osteochondral defects, caused by trauma, inflammation, or degenerative diseases, lead to joint dysfunction and disability. While biomimetic scaffolds can replicate the complex composition of native osteochondral tissue, they often fail to mimic its intricate and anisotropic nanostructure. In this study, we develop a highly biomimetic three-layer mineralized collagen scaffold featuring a wood-reinforced subchondral bone region (TMCWSB) for osteochondral tissue engineering. The scaffold comprises a superficial zone (SZ) of collagen, a middle zone (MZ) of collagen and hydroxyapatite, and a bottom zone (BZ) of wood, collagen, and hydroxyapatite. The organic content decreases and inorganic content increases progressively from SZ to BZ, closely mimicking the composition of native osteochondral tissue. The scaffold's structure replicates the interconnected porous network in the SZ and the directional pore architecture in the BZ, resembling the natural osteochondral microstructure. With enhanced mechanical properties from SZ to BZ, the TMCWSB scaffold demonstrates exceptional biocompatibility and bioactivity, effectively promoting the gradient differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage-bone phenotypes. This highly biomimetic TMCWSB scaffold offers a promising strategy for osteochondral defect repair and holds significant potential in tissue regeneration and osteoarthritis treatment.