Controlled Antibiotic Release From Emulsion-Loaded Alginate and Fibrin Hydrogels Using Ultrasound

Postoperative infections remain a major complication after spinal fusion surgery, often caused by biofilm-forming bacteria that resist short-term antibiotic prophylaxis. Vancomycin (VAN) is sometimes delivered locally during surgery; however, levels diminish rapidly, leaving patients vulnerable to late-onset infections. We developed a composite hydrogel integrating perfluorohexane-based emulsions within alginate or fibrin matrices to enable both sustained and ultrasound-triggered VAN release. Water-in-oil-in-water emulsions were prepared using fluorosurfactant-stabilized perfluorohexane as the volatile oil phase, then embedded in hydrogels and exposed to ultrasound (2.5 MHz, 5.5 MPa peak negative pressure) to initiate acoustic droplet vaporization for triggered release. Drug release was quantified spectrophotometrically and with fluorescent-labeled VAN, while antibacterial efficacy was tested against Staphylococcus aureus. Hydrogels directly loaded with free VAN exhibited burst release (~55%-67% within 24 h) followed by limited sustained release, which is suboptimal for prolonged coverage. In contrast, emulsion-loaded hydrogels reduced premature leakage, retaining > 70% VAN on Day 1 and providing gradual baseline release. Ultrasound application enhanced VAN release up to 8.75-fold in alginate and 27.5-fold in fibrin hydrogels after 7 days (p < 0.0001), supporting both continuous and on-demand delivery. Only alginate-emulsion hydrogels showed measurable antibacterial activity, as drug-matrix interactions in fibrin prevented release; ultrasound-treated samples displayed significantly greater efficacy over 7 days (p < 0.05 vs. no ultrasound). This dual-mode delivery platform enables spatial and temporal control of VAN release, combining early prophylaxis with ultrasound-triggered reinforcement, and holds promise for improving infection prevention in orthopedic surgeries by aligning drug delivery with clinical timelines.