An injectable and self-healing oxidized starch-gelatin composite hydrogel loaded with barium titanate for synergistic ultrasound-activated eradication of bacterial biofilms

Abstract Bacterial biofilms, particularly those associated with urinary catheters and neurogenic bladder, present a formidable challenge due to their tolerance to conventional antibiotics and the acidic microenvironment they create. Here, we developed an injectable, self healing, pH responsive composite hydrogel (BTO@DG) by incorporating piezoelectric barium titanate nanoparticles into a dynamic network of oxidized starch and gelatin. This hydrogel rapidly forms under mild conditions, adheres well to tissues, and can be injected through a needle. Upon ultrasound stimulation, the embedded BTO nanoparticles generate reactive oxygen species via a piezoelectric effect, achieving over 98% killing of E. coli and effective disruption of pre formed biofilms. Notably, the hydrogel degrades faster in the acidic biofilm environment (pH 5.5), enabling targeted drug release. Importantly, BTO@DG plus ultrasound treatment not only eradicates bacteria but also reduces excessive inflammation by suppressing the JAK1/STAT-1 pathway in macrophages, decreasing pro inflammatory cytokines. This dual action—direct antibacterial activity combined with anti inflammatory immunomodulation—positions BTO@DG as a promising non antibiotic platform for biofilm associated infections, particularly for minimally invasive bladder instillation therapy.