A Zn ²⁺ -Coordinated, HA-Reinforced Hierarchical Cellulose-Based Composite Hydrogel with Multifunctions

Current bone repair materials struggle to integrate mechanical support, bioactivity, and antibacterial function, particularly those capable of mimicking the multiscale structure and regulating the local ionic microenvironment of natural bone. Herein, a biomimetic multilevel composite hydrogel based on a natural luffa sponge (LS) was constructed by combining a Zn2+-coordinated LS framework (Zn-WLS) with a hydroxyapatite-reinforced poly(vinyl alcohol) hydrogel (HA-PVA). The Zn-WLS/HA-PVA composite hydrogel exhibited substantially enhanced mechanical properties: a compressive strength of 4.2 MPa and a Young’s modulus of 14.9 MPa at 70% strain, representing approximately 10-fold and 300-fold increases over the pure HA-PVA hydrogel, respectively. It also demonstrated high fatigue resistance and strain-responsive energy dissipation with an energy dissipation density of 23.23 kJ·m–3. In simulated body fluid, the composite hydrogel enabled relatively controlled Zn2+ release and active Ca2+ uptake, rapidly inducing the formation of a bioactive bone-like calcium-deficient apatite layer (Ca/P ≈ 1.5) on its surface. In vitro biological evaluations confirmed negligible cytotoxicity toward MC3T3-E1 preosteoblasts, significantly enhanced early osteogenic differentiation, further promoted matrix mineralization and collagen deposition at the late stage of osteogenesis, and markedly upregulated the osteogenesis-associated genes Runx2, ALP, COL, and OCN, and high broad-spectrum antibacterial efficacy against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) (>98.5% inhibition). Through a “molecular-nano-micro-macro” multiscale synergistic strategy, this work successfully fabricates a cellulose-based composite hydrogel that integrates high strength, controllable ion exchange, osteogenesis promotion, and antibacterial function, offering a promising design strategy for bone repair scaffolds with integrated mechanical and biological functions.