Oral ulcers compromise the quality of life of patients due to pain and recurrence. Conventional localized treatments are limited by the dynamic oral environment, resulting in insufficient drug penetration and short retention. Current treatment strategies primarily focus on alleviating clinical symptoms, often overlooking the pathological progression of oral ulcers. The core-shell microneedles (MNs) developed in this study employ a sequential drug release strategy to precisely match the distinct requirements of different ulcer healing stages. The outer hyaluronic acid (HA) shell rapidly dissolves and releases Menthol immediately, producing instant analgesic and cooling effects during the early stage of ulceration. The photocrosslinked gelatin methacryloyl (GelMA) hydrogel core loaded with glycyrrhizic acid (GA) provides a sustained release profile. This release counteracts inflammation, oxidative stress, and bacterial proliferation, while remodeling the pathological microenvironment to promote angiogenesis and cell migration. These combined actions sustain ulcer repair and enable a full‑course intervention from acute symptom relief to deep tissue regeneration. In addition, the hydroxypropyl trimethyl ammonium chloride chitosan (HACC) backing layer ensures effective adhesion and enhances antibacterial activity. By integrating rapid symptomatic relief with long-term regenerative therapy, this programmable release platform represents a transformative drug delivery strategy aligned with the pathological stages of oral ulcer healing, serving as a model with strong clinical prospects for next-generation treatments of oral diseases.

Persistent bacterial infection, oxidative stress imbalance, and cellular dysfunction within diabetic wound microenvironments represent key clinical challenges that hinder wound healing. To address these challenges, we developed a smart reactive oxygen species (ROS)-responsive bilayer thermoregulatory hydrogel, PP@PZC&SAg. The system was based on a dynamically cross-linked phenylboronate ester network. The in situ green synthesis of Ag nanoparticles endowed the hydrogel with highly efficient photothermal bactericidal capabilities, whereas the incorporated Zn/Ce layered double oxide nanozyme (PZC) mimicked catalase activity to scavenge excess ROS in the microenvironment. The top layer comprised a thermosensitive hydrogel that utilized its phase-change properties to precisely regulate photothermal temperatures, thereby effectively destroying bacterial biofilms while preventing thermal damage to surrounding tissues. The PP@PZC&SAg hydrogel system exhibited considerable photothermal activity, rapidly reaching and maintaining a stable operating temperature while simultaneously eliminating bacteria and disrupting biofilms. Furthermore, through synergistic ROS scavenging and the release of active Zn and Ce ions, this system restored endothelial cell proliferation, migration, and tubulogenic capacity, which are typically impaired under high-glucose conditions, ultimately promoting rapid diabetic wound healing. This approach simultaneously combats bacterial infections, alleviates oxidative stress, and restores cellular function, thereby offering a novel, multifaceted, and targeted therapeutic strategy for treating diabetic wounds.