Hydrogen-bonded organic framework-reinforced piezoelectric scaffolds for guided in situ bone regeneration

The fibrin network formed during the early bone repair establishes a viscoelastic micromechanical niche that recruits cells and releases cytokines, playing a pivotal role in primary callus formation. However, conventional metallic implants often lack these dynamic, bioactive cues due to their surface bioinertness. Furthermore, while piezoelectric coatings can mimic endogenous bioelectrical signals, their insulating properties and the Debye screening effect restrict stimulation to cells in direct interface contact, shielding the surrounding tissue. Herein, a biomimetic composite scaffold was prepared by anchoring a hydrogen-bonded organic framework (HOF, PFC-73-Cu) onto a piezoelectric BaTiO₃-coated titanium substrate. This design exerts dual synergistic functions: the PFC-73-Cu coating recruits fibrin to establish a native-like adhesive interface, while the BaTiO 3 layer yields piezopotentials under physiological loading to trigger mechano-electrical signaling. In vitro and in vivo evaluations confirmed that the HOF@BT/Ti scaffold significantly accelerates bone remodeling via the FAK and PI3K/AKT pathways. By coupling interfacial modulation with dynamic biomechanical stimulation, this work provides a robust strategy for designing next-generation intelligent orthopedic implants.