On April 29, the research team led by Professor Tao Chen and Associate Researcher Shanshan Hu from the Affiliated Stomatological Hospital of Chongqing Medical University published an online research paper in the internationally renowned journal Science Advances, titled “A Robust Adhesive Microneedle for Oral Infections Therapy via Synergistic Antibacterial and Neutrophil‑Macrophage Axis Immunomodulation.”
Oral infectious diseases (such as refractory ulcers, periodontitis, peri‑implantitis, etc.) face significant treatment challenges due to the humid, dynamic, and anatomically complex oral environment. Conventional mouthwashes, gels, or sprays fail to maintain effective drug concentrations at the lesion site. Moreover, single‑modal antibacterial therapy often neglects the restoration of immune homeostasis, leading to persistent inflammation and impaired tissue regeneration. Therefore, there is an urgent need for a novel therapeutic strategy that can both efficiently eliminate pathogens and intelligently regulate the local immune microenvironment.
Inspired by the wet adhesion mechanism of mussels, the team proposed a dual‑strategy biomimetic microneedle design combining "chemical bonding + geometric interlocking". Caffeic acid (catechol‑rich) was grafted onto a polyvinyl alcohol (PVA) backbone, and Fe₃(CO)₁₂ was introduced to form a dynamic metal‑coordination network. Meanwhile, three‑dimensional finite element analysis (3D‑FEA) was used to optimize the microneedle taper to 30°, achieving an optimal balance between adhesion strength and tissue penetration force. The microneedle achieved tight attachment on various oral mucosal surfaces and could firmly adhere to the rat oral mucosa for more than 4 hours under wet conditions, followed by natural degradation. Upon near‑infrared (NIR) irradiation, the microneedle simultaneously generated mild photothermal heat (50°C), triggered Fenton reaction to produce hydroxyl radicals (·OH), and released carbon monoxide (CO), forming a triple‑synergistic antibacterial network that achieved nearly 100% eradication of multiple oral pathogens and mature biofilms. In parallel, the system temporally regulated the neutrophil–macrophage axis — first activating phagocytosis, then inducing timely apoptosis, and recruiting macrophages for efferocytosis via "find‑me" signals, driving macrophage polarization toward a reparative phenotype and establishing a complete "kill‑clear‑repair" immune closed loop. In rat periodontitis, oral ulcer, and beagle dog mucosal defect models, the material significantly promoted bone regeneration and wound healing, with collagen maturation superior to commercial controls, and demonstrated favorable biosafety, providing a new strategy for oral infection therapy.
Shan Wang (Ph.D. candidate) and Yuan Chen (postdoctoral fellow) from the College of Stomatology are the co‑first authors of this paper. Professor Tao Chen and Associate Researcher Shanshan Hu are the co‑corresponding authors. This work was supported by grants including the National Natural Science Foundation of China Excellent Young Scientist Fund and the Chongqing Natural Science Foundation.
Original article link: https://www.science.org/doi/10.1126/sciadv.aee4401
(Translated by AI)
