Bacterial infection and oxidative stress are major barriers to wound healing,while conventional antibiotic therapies are constrained by cytotoxicity andantimicrobial resistance. Probiotic-based strategies present safer alternatives,yet most current efforts largely rely on single-strain systems with limitedfunctionality, as multi-strain combinations risk antagonism in complex woundenvironments. Herein, a dual-probiotic microsphere hydrogel is reportedfabricated via parallel microfluidic technology, where Lactobacillus reuteri andLactobacillus fermentum are individually encapsulated into distinctmicrospheres and integrated within a hydrogel matrix. By leveraging spatialseparation and functional complementarity, the hydrogel achievedoutstanding antibacterial efficacy of ≈97.8% against Gram-negative E. coliand ≈98.5% against Gram-positive S. aureus, together with strongantioxidant activity that reduces intracellular ROS by up to ≈83.9%. Notably,these multifunctional effects are realized without the use of any conventionalbiochemical antibiotics or antioxidants. In a full-thickness infected woundmodel, the dual-probiotic hydrogel markedly accelerated wound closure andenhanced tissue regeneration, outperforming single-strain controls, withcomplete closure achieved as early as day 8. This work demonstrates, for thefirst time, the full exploitation of dual probiotic synergy to achieve potentantibacterial, antioxidant, and wound-healing performances, highlighting apromising therapeutic platform for managing complex wound environments.

Bacterial infection; oxidative stress; tissue healing