Bioactive Glass-Reinforced Composite Bone Adhesive with pH Modulation, Mechanical Strengthening, and Antibacterial and Osteogenic Functions

The development of bone adhesives with high mechanical strength, controlled degradability, and bioactivity remains a formidable challenge in orthopedic repair. In this study, a bioactive glass (BG)-reinforced tetracalcium phosphate/O-phospho- l -serine/poly(acrylic acid) (TTCP/OPLS/PAA) composite adhesive was fabricated to address the acidity, limited bioactivity, and insufficient wet adhesion associated with existing formulations. Systematic optimization of BG, OPLS, and PAA ratios established a balanced coordination network among PAA carboxyl groups, OPLS phosphate groups, and Ca 2+ ions released from TTCP/BG. The optimized adhesive (B 5 O 30 T 95 P 60 ) exhibited strong initial bonding to bone and titanium, with compressive shear strength increasing to 7.36 MPa and compressive strength to 88.04 MPa after 24 h in simulated body fluid. BG addition effectively neutralized the acidic microenvironment (initial pH 6.50) and established a stable weakly alkaline milieu (pH 7.10–7.50), which is favorable to osteoblast proliferation and early osteogenesis. The adhesive showed rapid hydroxyapatite formation, steady mass loss over 8–12 weeks, and a degradation profile compatible with bone remodeling. Incorporation of vancomycin conferred potent antibacterial activity without compromising mechanical integrity, while coincorporation of bone morphogenetic protein-2 (BMP-2) further enhanced osteogenic performance. In a rat critical-sized femoral defect model, the BMP-2/vancomycin-loaded adhesive facilitated robust cortical bridging, higher bone volume fraction, reduced porosity, and nearly restored three-point bending strength relative to native bone, outperforming commercial PMMA bone cement. Overall, the BG-reinforced TTCP/OPLS/PAA adhesive integrates high-strength fixation, bioactivity, infection control, and osteoinductive capability, offering a promising platform for next-generation bone repair materials. Further evaluation in large animal models is warranted to support clinical translation.