Natural Bone Regeneration-Inspired Poly(Lipoic Acid)-Based Organic-Inorganic Bone Adhesive for Osteoporotic Bone Defect Repair.

Osteoporosis, featured by imbalanced bone remodeling, faces clinical challenges including microenvironment dysregulation, insufficient mineralization, and poor material fixation. Inspired by natural bone regeneration-where ossification centers and surrounding soft tissues orchestrate mineralization and tissue integration-we herein develop a biomimetic adhesive in which strontium titanate (SrTiO3) serves as the mineralization core to mimic ossification centers, boosting biomineralization and osteoblast differentiation. Meanwhile, poly(lipoic acid) (PolyLA), synthesized via one-step polymerization of lipoic acid (LA), replicates the role of soft tissues for structural support and biological regulation. Multiple coordination interactions between carboxyls and strontium ions substantially reinforce this organic-inorganic composite, resulting in a compressive strength, toughness, and tear resistance 11.65-fold, 9.1-fold, and 2.76-fold higher than those of pure PolyLA, respectively, thereby resisting anisotropic mechanical stresses at osteoporotic sites under physiological locomotion. Additionally, its hot-melt injectability enables robust interfacial fixation to osteoporotic bone, achieving an adhesion strength of up to 1.3 MPa, and facilitates sustained co-release of Sr2+ and LA, conferring anti-inflammatory, antioxidant, and pro-angiogenic functions. In an osteoporotic rat femoral defect model, this adhesive outperforms commercial bone cement by accelerating bone regeneration, improving microarchitecture, and increasing bone density. Its biocompatibility, degradability, mineralization capacity, and stable fixation offer a biomimetic strategy for osteoporosis treatment.