A multifunctional living hydrogel for the synergistic management of infected diabetic wounds

The primary causes of poor healing in diabetic wounds are bacterial infection, immune imbalance, and chronic inflammation. In this study, we employed the "fighting bacteria with bacteria" strategy to develop a dynamic living hydrogel system that comprehensively coordinates antibacterial, antioxidant, and regenerative functions for infectious diabetic wounds. Through engineered integration of functionalized probiotics and adaptive hydrogel networks, <i>Lactobacillus rhamnosus</i> CLK 101 (<i>LRh</i>) was biosynthesized with intracellular nano-selenium (nanoSe) and surface-coated with ceramide (CAD). The probiotics were then encapsulated within a biocompatible phospholipid polymer hydrogel that maintained probiotic viability. This living hydrogel system synergistically accelerated healing through multiple regulatory mechanisms. First, the probiotics exhibit inherent antibacterial properties, effectively eliminating Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) from the wound. Moreover, the intracellular nanoSe is released into the hydrogel, effectively scavenging excess reactive oxygen species (ROS). It also presents a synergistic effect with the probiotics by modulating macrophage polarization and reversing the inflammatory microenvironment of the wound. Finally, the ceramide coating plays a crucial role in restoring the barrier function of the skin. This novel strategy opens new avenues for living bacterial therapy as an effective treatment in the management of infected diabetic wounds.