High-resolution printing of a Schiff-base collagen I/alginate/oxidized hydroxylmethyl cellulose scaffold for enhanced osteogenic differentiation of mesenchymal stem cells

Collagen I is the key extracellular matrix (ECMs) compound in bone tissue and one of the most important biomaterials for bone tissue engineering applications. However, it was challenging to print its mesh scaffold with a high resolution presumably due to its relatively weak ink shape fidelity. Though existing studies attempted to solve this issue by increasing its ink viscosity, the improvement of printing resolution was still limited while the ink flowability was undesirably sacrificed. To solve the aforementioned problems, we blended oxidized cellulose with collagen I to form a Schiff-base interaction. The obtained hydrogel exhibited a lower viscosity but more apparent linear rheological characteristic according to our large amplitude oscillation test (LAOS) results, which achieved a printing resolution approaching 150 μm and reported one of the highest printing resolutions among collagen I-based scaffolds. Scaffolds with this scale of rod diameter and pore size greatly promoted the proliferation and osteogenic differentiation of MSCs. Osteogenic-related genes including N-cadherin, HIF-1α, and β-catenin were all upregulated in their expression. We believe this study would broaden our understanding towards scaffold design and processing optimization for bone tissue engineering applications.