High-resolution 3D printing of collagen I-based scaffolds via Schiff-base interaction for enhanced osteogenic differentiation

Collagen I is a key extracellular matrix (ECM) component in bone tissue and one of the most important biomaterials for bone tissue engineering applications. However, printing high-resolution mesh scaffold from collagen I remains challenging due to its relatively weak ink shape fidelity. While previous efforts have attempted to improve printability by increasing ink viscosity, such approaches often compromise ink flowability and yield only modest improvements in printing resolution. To solve this issue, we blended oxidized cellulose with collagen I to form a Schiff-base interaction. The resulting hydrogel exhibited lower viscosity but a more apparent linear rheological characteristic, as demonstrated by our large amplitude oscillation sweep results. This enhanced rheological profile enabled the fabrication of scaffolds with a printing resolution approaching 150 μm—one of the highest reported for collagen I-based scaffolds. Scaffolds with this scale of rod diameter and pore size greatly enhanced the proliferation and osteogenic differentiation of mesenchymal stem cells. Correspondingly, the expression of key osteogenic markers, including N-cadherin, HIF-1α, and β-catenin, was upregulated. These findings broaden our understanding of scaffold design and processing optimization of collagen I-based scaffolds and may advance their application in bone tissue engineering.

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