A study on the synergistic chondro-inductive effects of collagen II and its high-resolution 3D-printed scaffolds

Collagen II is the most essential component of the cartilage-specific extracellular matrix (ECM). However, research on collagen II-based scaffold fabrication, structural optimization, and correlation to the chondrogenic activities of stem cells is currently limited, presumably due to challenges related to its hydrogel processability. Existing collagen II-containing scaffolds are mainly produced by freeze-drying and exhibit limited properties, such as pore interconnectivity and tortuosity. Additionally, the chondro-inductive capability of collagen II composition and its underlying mechanism remains unclear, warranting further research. In this study, we addressed the aforementioned issues by investigating and enhancing the rheological properties of collagen II-based hydrogel, resulting in a high printing resolution exceeding 150 μm. The collagen II composition reportedly facilitated the condensation and chondrogenic activities of mesenchymal stem cells (MSCs) compared to gelatin. Moreover, high-resolution collagen II-based scaffolds promoted cell proliferation and chondrogenic differentiation to a higher degree. Therefore, we optimized the compositional and structural characteristics of collagen II-based scaffolds for enhancing chondrogenic activities. We anticipate that this study will broaden our understanding of collagen II-based scaffold designs and condition optimizations for cartilage tissue engineering.