Three-Dimensional Hierarchical Nanofibrous Collagen Scaffold Fabricated Using Fibrillated Collagen and Pluronic F‑127 for Regenerating Bone Tissue

It is well known that a nanoscale fibrous structure can provide a unique stage for encouraging reasonable cell activities including attachment and proliferation owing to its similar topological structure to the extracellular matrix. Hence, the structure has been widely applied in tissue regeneration. Type-I collagen has been typically used as a typical tissue regenerative material owing to its biocompatibility and abundance, although it has potential for antigenicity. In particular, collagen has been fabricated in two different forms, porous spongy and nanofibers. However, although the structures provided outstanding cellular activities, they exhibit disadvantages such as low cell migration capabilities in a spongy scaffold owing to the low degree of interconnected macropores and low processability in fabricating three-dimensional (3D) structures in an electrospun collagen scaffold. Hence, the fabrication of 3D nanofibrous collagen structures with interconnected macropores can be extremely challenging. In this work, we developed a 3D collagen scaffold consisting of multilayered nanofibrous struts fabricated using a 3D printing process and pluronic F-127 (PF-127), which is a thermoreversible polymer. After optimizing various processing conditions, we successfully achieved the 3D nanofibrous collagen mesh structure with fully interconnected macropores. A 3D-printed collagen scaffold that was fabricated using a low-temperature printing process was applied as a control. Through various analyses using physical properties (surface morphology, fibronectin absorption, mechanical properties, etc.) and cell activities using preosteoblasts (MC3T3-E1), we are convinced that the newly designed 3D nanofibrous collagen scaffold can be a new promising scaffold for bone tissue engineering.