Bio-inspired anisotropic eood-based hydrogel composites for bone repair

Natural materials generally have a multi-scale hierarchical anisotropic structure selected by natural evolution for achieving particular functionalities and properties. For example, bone consists of highly ordered staggered arrays of cross-linked collagen fibrils embedded with plate-like hydroxyapatite (HAp) nanocrystals. Such hierarchical anisotropic structure and precise organization of the organic and inorganic phases at the nanoscale offer an unique combination of exceptional mechanical properties and biological functions. Mimicking the bone with simultaneously achieved hierarchical anisotropic structure and remarkable mechanical properties remains a grand challenge.

Anisotropic hydrogels mimicking the biological tissues with directional functions play essential roles in damage-tolerance, cell guidance and mass transport. Conventional synthetic hydrogels often have isotropic network structure, insufficient mechanical properties and lack of bio-functionalities, which greatly limit their applications for load-bear tissue engineering. Inspired by natural bone and wood, we develop a biomimetic strategy to fabricate highly anisotropic, ultrastrong and stiff, and osteoconductive wood-based hydrogel composites via impregnation of biocompatible sodium alginate hydrogels into the delignified pinewood followed by in-situ mineralization of hydroxyapatite (HAp) nanocrystals. By delignification, the porous structure of the delignified wood significantly benefits the infiltration of alginate hydrogel. The well-aligned cellulose nanofibrils endow the hydrogel composites with highly anisotropic structural and mechanical properties. The strong intermolecular bonds of the aligned cellulose fibrils and alginate/cellulose interaction, and the reinforcing nanofillers of HAp enable the hydrogel composites remarkable tensile strength of 67.8 MPa and elastic modulus of 670 MPa, which exceed almost all the currently available strong hydrogels. The presented hydrogel composites exhibit not only strong and anisotropic mechanical properties, but also bone-mimicking structural and compositional characteristics. In vitro, this mineralized wood-based hydrogel (MWH) can promote pre-osteoblast adhesion, spreading, proliferation and osteogenic differentiation. In vivo, the MWH can accelerate bone regeneration and enhance new bone ingrown to the scaffold. Our study provides a low-cost, eco-friendly, feasible and scalable approach for fabricating anisotropic, strong, stiff, hydrophilic and osteoconductive hydrogel composites for bone repair.