Multifunctional core-shell microneedles with sequential release ability for oral ulcer healing

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.