Continuous Manufacturing of Bioinspired Bone-Periosteum Integrated Scaffold to Promote Bone Regeneration

The scaffold that bioinspired natural bone-periosteum is ideal for the repair of bone defects, while the achievement of a gradient scaffold with an integrated and stable interface remains challenging. Herein, a bioinspired bone-periosteum integrated collagen-based scaffold is developed, in which the top layer is electrospun collagen-dense scaffold as bioinspired periosteum (BP) to prevent invasion of reticular fiber tissue and the bottom layer is in situ mineralized collagen scaffold (IMCS) to promote osteogenic differentiation. Owing to the proposed continuous manufacturing of successive 3D printing and electrospinning, the integrated scaffold (BP-IMCS) comprised of BP and IMCS demonstrates excellent structural stability, ten times higher than that of direct-combination scaffolds. Besides, in vivo implantation results confirmed that BP-IMCS significantly improves new bone formation up to 32.47%, better than an individual layer, due to its co-work of mineral ions and bioinspired structure. Therefore, this study offers a continuous manufacturing strategy to realize the integrated and interface-stable bone-periosteum structure, providing new solutions for heterostructure tissue fabrication.