Bioprinting of Biomimetic Periosteum‐Bone Integrated Scaffolds

Bone is composed of periosteum, cortical bone, and cancellous bone. The development of tissue engineering scaffolds mimicking these three parts of bone tissue and enabling synergistic functional performance remains a significant challenge. Herein, a biomimetic periosteum-bone integrated scaffold was successfully fabricated by assembling the outer engineered periosteum with the inner Haversian bone module, achieving structural and functional biomimicry of natural bone tissue. The engineered periosteum constructed with periosteal cells (PCs) with zinc silicate nanorods (ZS) spontaneously recapitulated the diverse bioactivities of natural periosteum, thus facilitating the synergistic osteogenesis when co-cultured with bone marrow related cells in vitro. Coarse‑grained molecular dynamics simulations revealed that surface curvature of ZS affected membrane bending-energy landscape and particle reorientation during endocytosis, thereby regulating PCs' function via altered intracellular ion accumulation kinetics. Notably, in a segmental bone defect, the engineered periosteum and Haversian-bone module exhibited the superior synergistic effect on integrative bone regeneration in vivo. More importantly, the engineered periosteum was found to functionally replace natural periosteum with the mechanism of ZS activating a specific fibrogenic sub-cluster with potent chondrogenesis and neurovascular communication. This biomimetic periosteum-bone integrated scaffold offers a fresh perspective for the design of full structure and function-mimicking bone tissue engineering materials.