Dextran-based microneedle patch Co-delivering safflower polysaccharide and ROS-responsive tetramethylpyrazine micelles for diabetic wound repair

Diabetic wounds remain a major health concern due to impaired healing from persistent inflammation, oxidative stress, and compromised neurovascular regeneration. Conventional therapies are often insufficient to modulate the multifaceted pathological microenvironment of diabetic wound, underscoring the urgent need for multifunctional therapeutic strategies. In this study, we developed a polysaccharide-based hydrogel microneedle (MN) system, co-delivering tetramethylpyrazine (TMP) and safflower polysaccharide (SPS) to promote diabetic wound healing through reactive oxygen species (ROS)-responsive release and neurovascular regeneration. SPS was incorporated into a methacrylated dextran (DexMA)-based hydrogel matrix. Meanwhile, the hydrophobic TMP was encapsulated into ROS-responsive micelles formed by amphiphilic poly(propylene sulfide)-hyaluronic acid (PPS-HA), which served as both a redox-sensitive carrier and a hydrophilic polysaccharide component. The resulting D/SPS/T@P-H MN patch demonstrated strong mechanical integrity, dermal penetration capability, and sustained release behavior. In vitro studies showed robust antioxidant, anti-inflammatory, pro-angiogenic, and neuroregenerative activities. In vivo , the MN patch significantly accelerated wound closure in diabetic rat. Transcriptomic analysis further revealed the activation of key genes and signaling pathways involved in immune modulation and neurovascular repair. In summary, this work develops a multifunctional ROS-responsive hydrogel microneedle system that enables ROS-responsive drug delivery and synergistic tissue regeneration, offering a comprehensive materials-based solution for diabetic wound healing.