SrFeO-doped nano-layered double hydroxide/chitosan layered scaffolds with a nacre-mimetic architecture guide in situ bone ingrowth and regulate bone homeostasis.

Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFeO nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFeO-LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 ​MPa). The as-released Mg ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway. the Mg ions released from the SrFeO-LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1β and TNF-α), while the as-released Sr ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFeO-LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFeO-LDH/CS scaffolds. Hence, this study on multifunctional SrFeO-LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects.