Coaxial structured collagen-alginate scaffolds: Fabrication, physical properties, and biomedical application for skin tissue regeneration

Collagen is the most promising natural biomaterial and has been used in various tissue engineering applications for skin, bone, and cartilage because it provides good biocompatibility and low antigenicity. Although collagen is an excellent candidate material for various biomedical applications, its difficult processability and mechanical properties have remained important limitations. To overcome the problems, several methods including indirect printing combined with a sacrificing mold and low-temperature printing were suggested. However, it is difficult to fabricate precisely controlled 3D pore structure using the methods. In a previous study, we introduced a three-dimensional (3D) pore-structure-controlled collagen scaffold fabricated by a 3D dispensing system supplemented with a cryogenic and freeze-drying system. The fabricated scaffold had remarkably good cellular behaviour (cell migration and differentiation) but poor mechanical stability due to the highly porous structure consisting of micro-sized strands and poor mechanical nature of collagen. To overcome this deficiency, we designed a hybrid (core/shell) scaffold composed of an outer collagen and an inner alginate. The collagen/alginate scaffolds exhibited good structural stability (core-shell structure), increased Young's modulus about seven times compared to pure collagen scaffold under a similar pore-structure, and resulted in good cell viability, similar to a pure collagen scaffold. In an in vivo test, the hybrid scaffold was used as a dermal substitute and provided good granulation tissue formation and rapid vascularisation.