ABSTRACTObjectivesThis study aimed to explore multiple effects of hyperbranched poly‐l‐lysine (HBPL) titanium (Ti) surfaces on osseointegration, bacteriostasis, and anti‐inflammation across three different animal models.MethodsTi surfaces were covalently modified with HBPL, with uncoated surfaces as controls. Characterization included scanning electron microscopy (SEM) and surface chemistry and elemental analysis (EDX). Ti and Ti‐HBPL implants were placed in conventional canine edentulous sites, post‐operative infection canine edentulous sites, and diabetic rat tibias. Implants from canine edentulous models were analyzed using micro‐CT and histomorphometry to assess osseointegration at 8 weeks. Post‐operative infection beagles were used to evaluate antibacterial efficacy through clinical parameters and bacterial cultures at 1 week. In diabetic rats, micro‐CT and histomorphometry were performed at 8 weeks.ResultsHBPL was uniformly grafted on Ti‐HBPL surfaces. Ti‐HBPL surfaces showed higher bone volume/total volume (BV/TV, p < 0.001), bone‐implant contact (BIC%, p < 0.001), and trabecular number (Tb.N, p < 0.01) in beagles. Besides, it displayed higher BIC% (p < 0.001) and bone area fraction occupancy (BAFO%, p < 0.01) in hard tissue sections. In an infected model, Ti‐HBPL surfaces exhibited lower bleeding on probing (BOP, p < 0.001), and plaque index (DI, p < 0.01), with reduced bacterial colony formation (p < 0.001) compared to the control group. In diabetic rats, Ti‐HBPL surfaces showed an increase in BV/TV (p < 0.01) and Tb.N (p < 0.001), downregulated TNF‐α and IL‐1β (p < 0.01), and upregulated IL‐10 (p < 0.01) and osteocalcin (OCN) expression (p < 0.01).ConclusionsHBPL‐Ti surfaces demonstrated enhanced osseointegration, bacteriostasis, and anti‐inflammatory effects in vivo.