An ROS-Scavenging Treg-Recruiting Hydrogel Patch for Diabetic Wound Healing

Chronic inflammation and excessive reactive oxygen species (ROS) can impair diabetic wound healing. Regulatory T cells (Tregs) have emerged as a promising target to promote wound healing by regulating the immune system and supporting tissue repair through the secretion of growth factors and cytokines. However, an effective strategy for the on-demand recruitment of Tregs for wound healing is still lacking. Here, an ROS-scavenging Tregs-recruiting hydrogel patch is developed for the sequential release of CC motif chemokine 22 (CCL22) triggered by the ROS in the diabetic wound bed. The hydrogel patch is prepared by crosslinking the gelatin with ROS cleavable linker together with CCL22 (RSG-CCL22). RSG-CCL22 presented desirable physical properties suitable for skin regeneration purposes. In addition, the ROS scavenging feature of the RSG suppresses the differentiation of T helper 17 (Th17) cells and protects the recruited Tregs from apoptosis and oxidative stress, which maximizes their function in accelerating wound closure and promoting hair follicle regeneration in a diabetic full-thickness skin defect mouse model. Therefore, the proposed approach provides a new therapeutic strategy for tissue regeneration and wound repair via effective recruitment of functional Tregs through ROS-triggered on-demand delivery. To promote the healing of diabetic wounds, an ROS-responsive Tregs recruiting hydrogel patch is developed with gelatin backbone and crosslinked with CC motif chemokine 22 (CCL22) using a ROS cleavable linker. With the on-demand Tregs recruitment and ROS scavenging functions, this patch can suppress the overactive immune reactions and promote wound closure and hair follicle regeneration. image