Templated Assembly of Collagen Fibers Directs Cell Growth in 2D and 3D

Collagen is widely used in tissue engineering and regenerative medicine, with many examples of collagen-based biomaterials emerging in recent years. While there are numerous methods available for forming collagen scaffolds from isolated collagen, existing biomaterial processing techniques are unable to efficiently align collagen at the microstructural level, which is important for providing appropriate cell recognition and mechanical properties. Although some attention has shifted to development of fiber-based collagen biomaterials, existing techniques for producing and aligning collagen fibers are not appropriate for large-scale fiber manufacturing. Here, we report a novel biomaterial fabrication approach capable of efficiently generating collagen fibers of appropriate sizes using a viscous solution of dextran as a dissolvable template. We demonstrate that myoblasts readily attach and align along 2D collagen fiber networks created by this process. Furthermore, encapsulation of collagen fibers with myoblasts into non-cell-adherent hydrogels promotes aligned growth of cells and supports their differentiation. The ease-of-production and versatility of this technique will support future development of advanced in vitro tissue models and materials for regenerative medicine.