A Bioactive Polyurethane Adhesive Delivers Interfacial Mechano-Biochemical Cues for Meniscus Tear Repair

Meniscus repair is often limited by poor intrinsic healing, an adverse oxidative-inflammatory microenvironment, and insufficient mechanical continuity across the tear interface. Here, we engineered a solvent-free injectable polyurethane adhesive (PUA) loaded with connective tissue growth factor (PUA@CTGF) for meniscus tear repair that combines rapid wet interfacial stabilization, compliant defect filling, and prolonged CTGF release. The adhesive showed rapid in situ curing, high apparent initial wet lap-shear strength, and stable short-cycle compressive behavior in a 100-cycle loading-unloading test. In vitro, PUA@CTGF reduced oxidative stress-associated mitochondrial injury, modulated macrophage-associated inflammatory markers toward a more repair-supportive profile, promoted meniscal cell migration, and enhanced fibrochondrogenic matrix synthesis when combined with cyclic tensile stimulation. In a rabbit outer-vascular-zone meniscus tear model, PUA@CTGF improved repair-region continuity, matrix deposition, and tensile properties and attenuated early joint degenerative changes relative to untreated, suture, fibrin, and PUA controls, although native meniscal tensile properties were not fully restored during the 12-week observation period. Transcriptomic profiling identified mechanotransduction-related signatures, while inhibitor-supported in vitro analyses showed that GsMTx4 attenuated dynamic-loading-induced Ca²⁺ and YAP responses, supporting a GsMTx4-sensitive mechanotransduction response. These findings support PUA@CTGF as a bioactive polyurethane adhesive platform for wet, mechanically active meniscal repair interfaces. STATEMENT OF SIGNIFICANCE: Meniscus tears are difficult to heal because the injured interface is wet, mechanically active, and biologically hostile. This study introduces a solvent-free injectable polyurethane adhesive that rapidly stabilizes wet meniscal tears while providing localized delivery of connective tissue growth factor. By combining catechol-assisted wet adhesion, compliant defect filling, short-cycle energy dissipation, reactive oxygen species buffering, and prolonged CTGF release, the adhesive provides interfacial stabilization and microenvironmental regulation. In vitro and rabbit studies showed enhanced cell migration and matrix-associated responses, improved repair-region continuity and tensile properties, and attenuation of early joint degenerative changes. This work advances biomaterial design by integrating wet interfacial stabilization with localized biochemical delivery for the repair of mechanically active, load-bearing soft-tissue interfaces.