Constructing highly bioactive and tough polyurethane bone adhesives by covalently integrating nanohydroxyapatite

Achieving both robust mechanical and osteogenic properties of bone adhesives remains challenging. Here, we developed a novel polyurethane-based bone adhesive (PCLU- g -nHA) by covalently incorporating aminated nanohydroxyapatite (nHA-NH 2 ) into a biodegradable poly (ε-caprolactone) urethane (PCLU) network. This design promoted uniform nHA dispersion and strong organic–inorganic integration through urea linkages, significantly enhancing compressive modulus (4.91 ± 0.10 MPa) and adhesive strength (3.41 ± 0.24 MPa in lap-shear). The adhesive cured rapidly under mild conditions with minimal heat release. PCLU- g -nHA showed improved biocompatibility and stimulated bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in vitro . Transcriptomics revealed upregulation of extracellular matrix remodeling and collagen synthesis pathways. In vivo , PCLU- g -nHA enhanced bone regeneration and osseointegration in rabbit femoral condyle defect and tibial fracture models, outperforming a commercial PMMA bone cement. This study offers a scalable strategy for developing highly bioactive and tough bone adhesives with clinical translational potential.