Covalent Organic Framework Biomaterial Enhances Osteogenesis via Wnt/β-Catenin Pathway Activation

Bone defects caused by trauma, tumors, and degenerative diseases remain a major clinical challenge, necessitating effective strategies for bone repair. Traditional bone grafting approaches are limited by issues such as donor scarcity and immune rejection, highlighting the need for alternative strategies. Stem cell-based regenerative therapies, particularly those utilizing bone marrow mesenchymal stem cells (BMSCs), offer promising solutions due to their osteogenic potential. Herein, we report the synthesis of a porous and biocompatible nanostructured COF-Imine material and systematically evaluate its ability to promote BMSC osteogenic differentiation for bone regeneration. Our findings demonstrate that COF-Imine significantly enhances osteogenesis by activating the Wnt/β-catenin signaling pathway through multiple mechanisms, which facilitates the expression of key osteogenic genes such as ALP, OCN, COL1, and Runx2. In vivo experiments using a rat calvarial defect model further confirm that COF-Imine accelerates bone defect repair, underscoring its potential as a biomaterial for bone tissue engineering applications.