Bone adhesive with temporally-synchronized degradation for enhanced osteointegration.

Abstract

Bone adhesives have emerged as promising alternatives for complex fracture fixation. However, discrepancies between material degradation rates and the physiological timeline of bone healing remain a critical limitation. Here, a polyurethane-based adhesive (TNC) was developed, synthesized from trimeric hexamethylene diisocyanate, nano-hydroxyapatite, and type I collagen. The TNC demonstrates strong initial adhesion to both wet and blood-contaminated bone surfaces and exhibits excellent biocompatibility. A distinguishing feature of TNC is its capacity to synchronize degradation with the stages of bone healing. During degradation, TNC forms a mineralized surface layer that releases calcium ions. The calcium ions activate cathepsin K, an enzyme integral to bone remodeling. This calcium-mediated mechanism accelerates TNC degradation by 1.9-fold during the remodeling phase compared to the initial phase. In a rat skull fracture model, TNC supported effective fracture stabilization and achieved favorable bone regeneration at 8 weeks after implantation. These findings demonstrate that TNC combines early mechanical stability with phase-specific degradability to facilitate bone regeneration in a temporally-controlled manner. The present work provides a framework for the development of bio-responsive bone adhesives that synchronize degradation behavior with healing phases for orthopedic applications.