Mimicking DOUGONG brackets orchestrate regulating inflammation and mechanical stimuli for osteochondral regeneration using 3D printing

The microstructure of scaffolds is essential for enhancing cell-extracellular matrix interactions, which are critical for osteochondral regeneration. This study investigates the innovative use of 3D printing to mimic DOUGONG brackets to achieve this goal. Composite scaffolds of β-tricalcium phosphate, akermanite (AKer), and strontium silicate (SrSiO 3 ) at 1%, 5%, and 10% concentrations were fabricated via 3D printing. The osteogenic differentiation effects on bone marrow mesenchymal stromal cells and chondrogenic promotion effects on chondrocytes of different scaffolds were analyzed in vitro. An osteochondral defect model was created in SD rat knee joints, and various scaffold materials were implanted to evaluate their repair and anti-inflammatory effects. Characterization showed that SrSiO 3 composite scaffolds had uniform pore structures and high porosity with improved mechanical properties and sustained strontium ion release capacities. The Aker/Sr5% scaffold significantly enhanced cell viability and proliferation, inhibited apoptosis, and upregulated osteogenic markers (RUNX2, COL1A1, OCN, OPN) while downregulating inflammatory factors (IL-6 and TNF-α). This scaffold also improved the chondrocyte phenotype as indicated by increased chondrogenic markers (COL2A1 and SOX9). Additionally, it excelled in bone volume, bone mineral density, and tissue repair scores. The DOUGONG-inspired AKer/SrSiO 3 composite scaffold promotes osteochondral regeneration by enhancing osteogenesis via the PI3K/Akt signaling pathway and cytokine-cytokine receptor interaction, while simultaneously facilitating cartilage repair by promoting chondral phenotypes. This work provides a theoretical basis and new strategies for the clinical transformation of osteochondral repair.