Strontium-Loaded Chitosan/Wood Hydrogel with Anisotropic Cellular Architecture for Enhanced Critical Bone Regeneration

The reconstruction of critical-sized bone defects remains a significant clinical challenge. Natural polymers used for bone defects exhibit excellent biocompatibility and degradability; however, their inadequate mechanical properties, absence of biomimetic topological structures, and limited osteogenic potential hinder their suitability for clinical applications. In this study, we developed an all-natural wood hydrogel by integrating natural lignocellulosic nanofibers into chitosan hydrogels through delignification and vacuum impregnation. The all-natural wood hydrogel effectively mimics the structure of natural bone. Strontium ions mimicked bone's phosphate fibers, chitosan hydrogels emulated collagen fibers, and WW was used to recreate the layered, anisotropic bone tissue structures. Furthermore, the tensile strength of the all-natural wood hydrogel reached approximately 12 MPa, demonstrating a significant improvement in the mechanical strength. In vitro experiments confirmed that the all-natural wood hydrogel showed excellent biocompatibility, promoting cell proliferation and migration. Additionally, the release of strontium ions from the all-natural wood hydrogel supports angiogenesis and osteogenesis. Transcriptomic analysis initially revealed that the all-natural wood hydrogel modulates BMSCs activity by upregulating angiogenic and osteogenic genes while activating PI3K-AKT and calcium signaling pathways. Moreover, in in vivo experiments, this all-natural wood hydrogel is adaptable to various cranial defects and accelerates the repair of critical-sized bone defects. These findings offer insights into the development of all-natural wood hydrogels for enhancing bone regeneration.