Robust adhesive, antibacterial, pro-angiogenic and osteogenic bone adhesives with moderate degradability facilitating bone regeneration

Conventional bone repair technologies such as using metal implants and autologous bone grafts, are limited due to immune rejection, donor availability, the need for secondary surgeries, and material fatigue. Here, we demonstrated a novel multifunctional bone adhesive by mixing poly (ethylene glycol) succinimidyl glutarate (PEG-SG) with tannic acid (TA), copper oxide (CuO), bioactive glass (BG), and gelatin for sealing cranial defects and facilitating bone regeneration. In the porous bone adhesive, the PEG-SG was formed into an interconnected matrix, while TA served as a polyphenolic crosslinker that reinforced interfacial adhesion and mechanical strength. The PEG-SG/TA/CuO/BG/Gel bone adhesive was biodegradable and bioactive by releasing Cu 2+ and Ca 2+ that promoted angiogenesis, osteogenesis, and broad-spectrum antibacterial activity. The bone adhesive demonstrated instant and robust tissue adhesion (∼100kPa) within 60 seconds of contact with bone, and exhibited antibacterial efficiencies of Escherichia coli ( E.coli ), Staphylococcus aureus ( S.aureus ) and Methicillin-resistant Staphylococcus aureus ( MRSA ) (∼80%), while up-regulating osteogenic markers ( e.g. , collagen type I, osteocalcin). In a rat cranial defect model, the bone adhesive showed remarkable healing compared to commercial product poly (methyl methacrylate) (PMMA) and controls. Micro-CT and histology revealed significantly higher bone volume fraction (BV/TV), bone mineral density, and dense collagen matrix in the bone adhesive. Immunofluorescent staining of CD163 and TNF-α indicated a favorable osteo-immunomodulatory performance using the bone adhesive, as well as facilitating bone regeneration, as displaying enhanced CD31, collagen type I and osteocalcin expressions. Transcriptomic profiling of healing tissue further identified activation of PI3K-Akt and calcium signaling pathways, which motivated inflammation modulation and osteogenesis. These results highlighted the PEG-SG/TA/CuO/BG/Gel as a promising strategy for cranial bone repair and broader regenerative medicine applications. • A multifunctional PEG-based bone adhesive was developed for bone regeneration, integrating tannic acid (TA), copper oxide (CuO), bioactive glass (BG), and gelatin. • The bone adhesive exhibited strong and instant adhesion to bone (∼100 kPa within 60 s), antibacterial efficiency (∼80 %). • Sustained release of Cu 2+ and Ca 2+ ions promoted angiogenesis and osteogenesis. • In vivo studies showed accelerated bone repair, collagen deposition, and immune modulation than commercial bone cement products.