Functionalized hydrogel sequentially deliver tannic acid and bioactive probiotics for radiation-induced skin injury

As skin injuries caused by radiotherapy can significantly impede the healing process, it is essential to eliminate the interference of excessive reactive oxygen species (ROS) in the treatment of radiation-induced skin injury (RISI). To address this, we developed a temporally programmed hydrogel designed to enhance RISI repair, which was synthesized through the assembly of <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>) and tannic acid (TA)-loaded hydrogel (Gel/LT). These hydrogels demonstrated satisfactory free radical scavenging capacity in the early stages, achieving an effective clearance rate of 93.3 %, thereby reducing the production of ROS associated with RISI. Furthermore, the <i>L. reuteri</i> encapsulated by metal-polyphenol self-assembly is released at the wound site in response to the wound microenvironment, promoting angiogenesis and tissue regeneration. Both <i>in vitro</i> and <i>in vivo</i> experiments demonstrated that Gel/LT achieved ROS scavenging and tissue repair effects at different stages of RISI. The transcriptome results indicate that these hydrogels facilitate a transition from an immune response to cellular proliferation by reducing oxidative stress and upregulating the expression of anti-inflammatory genes. Additionally, they promote the regeneration of extracellular matrix components, such as collagen, ultimately achieving superior repair efficacy compared to the commercial drug amifostine. This hierarchical therapeutic strategy permits temporal drug delivery at various stages of the repair process, presenting a novel approach for the treatment of RISI.