The clinical management of complex fractures presents significant challenges. Traditional internal fixation methods are associated with drawbacks such as tissue damage, poor reduction, device failure, and stress shielding, which can ultimately lead to nonunion and delayed healing. Existing bone adhesives are limited in terms of tissue adhesion, biocompatibility, biodegradability, and osteoinductive activity. Effectively fixing and treating complex fractures remains an urgent clinical problem. This study proposes an organic-inorganic dual biomimetic strategy, utilizing caffeic acid-grafted collagen (CAC), aminated nanoclay (ALAP), and tetra-armed PEG-NHS (tetra-PEG-SC) to construct a multiple cross-linked network that provides wet adhesion and antioxidant properties while enhancing mechanical performance and osteogenic activity (Figure. 1). The aim is to develop a bone adhesive (CPA) with strong adhesion, controllable degradation, biosafety, and osteogenic activity, with the goal of addressing the challenges of fixation and healing in complex fractures. The results demonstrate that CPA exhibits strong mechanical properties and rapid wet adhesion. Additionally, CPA shows significant antioxidant capacity and pro-angiogenic activity, reshaping the anti-inflammatory microenvironment by downregulating the M1 macrophage marker CD68 and upregulating the M2 markers CD206/CD31, thereby accelerating bone healing. In vivo experiments confirmed that the CPA group achieved near-complete healing at 8 weeks and completed bone remodeling at 12 weeks, with mechanical strength close to that of normal bone. This study successfully developed a bioactive bone adhesive that, through an organic-inorganic composite network, achieves excellent adhesion in wet environments and resistance to fatigue, meeting the requirements for immediate intraoperative fixation. In an animal comminuted fracture model, CPA significantly promoted bone healing (8 weeks) and avoided the risks of foreign body reaction and nonunion. This material provides an integrated solution combining mechanical fixation and biological repair for complex fractures, demonstrating significant potential for clinical translation.

Bone Adhesive, Hydrogel, Fracture, Bone Repair