Zhang Qiqi, Liu Di, Gao Jingxian, Wu Xueling, Hu Wenxiu, Han Lu
Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao, 266237, China.
Mater Today Bio. 2025 Jul 22;34:102126. doi: 10.1016/j.mtbio.2025.102126. eCollection 2025 Oct.
Oral mucositis (OM), a prevalent and debilitating complication in patients undergoing chemotherapy or radiotherapy, is characterized by persistent neuropathic pain and impaired food intake. Conventional treatments are often limited by poor mucosal adhesion in the dynamic, saliva-rich oral environment. To address this challenge, we developed a mussel-inspired robust wet adhesive hydrogel via cholesterol micelle rearrangement, in which negatively charged catechol-functionalized hyaluronic acid (HD) forms a polyelectrolyte network with positively charged polyethyleneimine (PEI), triggering cholesterol-micelle chain rearrangement and directional surface micelle aggregation to achieve hydrophobic hydrogel surface. This mechanism enables robust wet adhesion (>10 kPa in artificial saliva) without pre-treatment or toxic crosslinkers. The hydrogel with mechanical compliance ensures seamless adaptation to oral tissue dynamics, functioning as a protective barrier against food-induced mechanical/chemical insults while enhancing lidocaine bioavailability. Synergizing catechol-mediated antioxidative activity (DPPH radical scavenging: >70 %) with sustained lidocaine release, the hydrogel can relieve pain and accelerate mucosal repair in 7 days by promoting epithelial regeneration, angiogenesis, and neurogenesis. This work presents a novel strategy for designing orally adaptive biomaterials, merging wet adhesion, drug delivery, and tissue remodeling into a single platform for effective OM management.
口腔黏膜炎（OM）是接受化疗或放疗患者中一种常见且使人衰弱的并发症，其特征为持续性神经性疼痛和食物摄入受损。在动态、富含唾液的口腔环境中，传统治疗方法常常因黏膜附着力差而受到限制。为应对这一挑战，我们通过胆固醇微胶粒重排开发了一种受贻贝启发的强力湿黏附水凝胶，其中带负电荷的儿茶酚功能化透明质酸（HD）与带正电荷的聚乙烯亚胺（PEI）形成聚电解质网络，引发胆固醇微胶粒链重排和定向表面微胶粒聚集，从而实现水凝胶表面的疏水性。这种机制无需预处理或有毒交联剂即可实现强力湿黏附（在人工唾液中>10 kPa）。具有机械顺应性的水凝胶可确保无缝适应口腔组织动态变化，充当抵御食物引起的机械/化学损伤的保护屏障，同时提高利多卡因的生物利用度。该水凝胶将儿茶酚介导的抗氧化活性（DPPH自由基清除率：>70%）与利多卡因的持续释放相结合，通过促进上皮再生、血管生成和神经生成，可在7天内缓解疼痛并加速黏膜修复。这项工作提出了一种设计口腔适应性生物材料的新策略，将湿黏附、药物递送和组织重塑整合到一个单一平台，以有效管理口腔黏膜炎。
