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, Lactobacillus rhamnosus CLK 101 ( LRh ) 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 Staphylococcus aureus (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. Illustration of this work: (a) Preparation of multifunctional LRh ( F -LRh) : Lactobacillus rhamnosus CLK101 is co-cultivated with sodium selenite (Na 2 SeO 3 ) to facilitate the intracellular synthesis of nanoSe, followed by the coating of the bacterial surface with ceramide. (b) Construction of the living hydrogel: The phospholipid polymer (PMBV) forms a dynamic cross-linked network with polyvinyl alcohol (PVA), embedding the modified probiotics to create a multifunctional living hydrogel system. The favorable biocompatibility of PMBV positively influences the physiological functions of the probiotics. (c) The gel@F- LRh promotes the healing of infectious diabetic wounds. In the model, the living hydrogel boosts chronic wound healing through several regulatory mechanisms, including antimicrobial action, ROS clearance, modulation of the inflammatory microenvironment of the wound, and restoration of skin barrier function.