Caffeic acid stabilized polylipoic acid/silk fibroin biopatch orchestrates synergistic robust wet adhesion, controlled anesthetic drug delivery, antioxidant, and inflammatory regulation for intraoral tissue repair. Chemical Engineering Journal 2026, 537, 176253.

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Zirong Zhao, Wenxiu Ma, Jiayang Li, Silei Li, Xinyi Wu, Bitao Lu, Kun Yu, Fei Lu, Ruiqi Xie, Dahua Shou, Enling Allen Hu, Jing Xie, Yuanchi Zhang, and Wan Wu.

Introduction

Oral ulcers pose significant clinical challenges due to the moist, dynamic environment of the oral cavity, which leads to poor adhesion and rapid washout of conventional dressings. This study developed a multifunctional mucoadhesive patch, (CMC/CS@Lid)@PLAca-SF, integrated with lidocaine-loaded microspheres to provide synergistic therapeutic effects. The adhesive patch matrix, synthesized via green chemistry from α-lipoic acid, caffeic acid, and silk fibroin, utilizes dynamic covalent crosslinking to achieve superior mechanical properties, including high tensile strength (564 kPa), excellent extensibility (>1200%), and rapid self-healing. Characterization confirmed stable covalent integration and robust wet adhesion (36.4 kPa) through multiple interactions. To address pain, pH-responsive CMC/CS microspheres were embedded to ensure sustained, localized lidocaine release specifically within the acidic ulcerative microenvironment. Experimental evaluations demonstrated broad-spectrum antibacterial activity, efficient ROS scavenging (>90%), and high biocompatibility. In a rat oral ulcer model, the patch significantly accelerated re-epithelialization (99.7% healing by day 8) and modulated the immune microenvironment by promoting M2 macrophage polarization. This innovative strategy offers a comprehensive approach to oral mucosal repair, combining protection, analgesia, and regenerative bioactivity.

中文介绍

口腔溃疡因口腔内潮湿且动态变化的环境而面临显著的临床挑战，这种环境会导致传统敷料黏附性差并快速被冲刷流失。本研究开发了一种多功能黏膜黏附贴片 (CMC/CS@Lid)@PLAca-SF，并将载利多卡因微球整合其中，以提供协同治疗效果。该黏附贴片基质通过绿色化学方法由 α-硫辛酸、咖啡酸和丝素蛋白合成，利用动态共价交联实现优异的力学性能，包括高拉伸强度 (564 kPa)、出色的延展性 (>1200%) 和快速自愈能力。表征结果证实，该体系具有稳定的共价整合结构，并通过多重相互作用实现了强韧的湿态黏附性能 (36.4 kPa)。为缓解疼痛，研究中嵌入了 pH 响应性 CMC/CS 微球，以确保利多卡因在酸性溃疡微环境中实现持续、局部释放。实验评价显示，该贴片具有广谱抗菌活性、高效 ROS 清除能力 (>90%) 和良好的生物相容性。在大鼠口腔溃疡模型中，该贴片显著加速了再上皮化过程（第 8 天愈合率达 99.7%），并通过促进 M2 型巨噬细胞极化调控免疫微环境。该创新策略为口腔黏膜修复提供了一种综合性方案，兼具保护、镇痛和再生活性。