Dual-Biomimetic Bone Adhesive with Osteoimmunomodulatory Capabilities for Anatomical Reconstruction of Comminuted Fractures.

Abstract

The development of bone adhesives capable of restoring natural bone structure and function represents a pioneering advancement in surgical technology, offering significant potential to improve the treatment outcomes of comminuted fractures. However, the development of a clinically demand-driven adhesive, ensuring both reliable adhesion and osteogenic activity, poses a significant challenge. Herein, a structurally and functionally dual-biomimetic bone adhesive is developed through the design of an organic-inorganic network-enhanced hydrogel, which integrates caffeic acid-grafted collagen (CAC), aminated laponite (ALAP), and N-hydroxysuccinimide ester-terminated polyethylene glycol (tetra-PEG-SC). Benefiting from nanosheet-induced strengthening, the mechanically reinforced adhesive can maintain integrity under extreme compression (98%) and tensile (600%) deformations, facilitating anatomical repositioning of rabbit radius and porcine femur fractures. Of greater importance, the adhesive accelerated fracture healing, potentially via ROS scavenging and immunomodulation, as evidenced by reduced oxidative stress and M2 macrophage polarization in vitro. Assessed through an innovative rabbit radius comminuted fracture model, the injectable bone adhesive demonstrates rapid and flexible adhesion of bone fragments in a blood-rich environment, as observed over the 2 fold improvement in biomechanical and radiological performance compared with commercially available cyanoacrylate adhesives. This intricately designed bone adhesive holds promise as a novel solution for addressing complex fracture cases in surgical treatment.