Lin Pochun, Cai Yimeng, Feng Ning, Yu Leixiao, Cao Shuqin, Yuan Quan
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109, United States.
ACS Appl Mater Interfaces. 2025 Jul 2;17(26):37617-37630. doi: 10.1021/acsami.5c06212. Epub 2025 Jun 16.
Oral mucosal lesions present significant therapeutic challenges due to the complex oral environment and limitations of conventional biomaterials in clinical application. In this study, we introduced an innovative tannic acid-reinforced gelatin hydrogel (Gel-TA) incorporated with cannabidiol (CBD), engineered as a multifunctional dressing to address antioxidant, anti-inflammatory, and analgesic requirements for oral wound management. The Gel-TA hydrogel was constructed through noncovalent interactions, including hydrogen bonding, hydrophobic interactions, and π-π stacking, resulting in a significantly enhanced compressive modulus and improved mucosal adhesion strength compared with pure gelatin. The gel-sol transition temperature increased to approximately 44 °C, rendering it suitable for application in the oral environment. CBD encapsulation enabled sustained drug release kinetics, achieving and maintaining therapeutic concentrations (85% cumulative release over 24 h) in artificial saliva. studies demonstrated that the hydrogel significantly accelerated wound healing and enhanced epithelial regeneration, with treated wounds achieving 73.4% closure within 3 days compared to 45.1% in untreated controls ( < 0.05). Histopathological analysis revealed a 60.05% reduction in inflammatory cytokine infiltration and a 2.8-fold increase in collagen deposition. The dual-action therapeutic platform combined structural stability with bioactive functionality, creating a protective niche that modulated the wound microenvironment through via three synergistic mechanisms: (1) mechanical barrier formation, (2) oxidative stress mitigation (93.8% ROS scavenging capacity), and (3) prolonged analgesic efficacy. This rationally designed hydrogel system offered a clinically translatable solution for oral mucosal regeneration, addressing both biological healing requirements and patient comfort through its tunable physicochemical properties and controlled therapeutic delivery.
由于口腔环境复杂以及传统生物材料在临床应用中的局限性，口腔黏膜损伤带来了重大的治疗挑战。在本研究中，我们引入了一种创新的鞣酸增强明胶水凝胶（Gel-TA），并掺入了大麻二酚（CBD），将其设计成一种多功能敷料，以满足口腔伤口管理中的抗氧化、抗炎和镇痛需求。Gel-TA水凝胶通过包括氢键、疏水相互作用和π-π堆积在内的非共价相互作用构建而成，与纯明胶相比，其压缩模量显著提高，黏膜粘附强度也得到改善。凝胶-溶胶转变温度升高至约44°C，使其适合在口腔环境中应用。CBD包封实现了持续的药物释放动力学，在人工唾液中达到并维持治疗浓度（24小时内累积释放85%）。研究表明，该水凝胶显著加速了伤口愈合并增强了上皮再生，与未处理的对照组相比，处理后的伤口在3天内实现了73.4%的闭合，而未处理对照组为45.1%（P<0.05）。组织病理学分析显示炎症细胞因子浸润减少了60.05%，胶原蛋白沉积增加了2.8倍。这种双作用治疗平台将结构稳定性与生物活性功能相结合，通过三种协同机制创建了一个调节伤口微环境的保护性微环境：（1）形成机械屏障，（2）减轻氧化应激（ROS清除能力达93.8%），以及（3）延长镇痛效果。这种合理设计的水凝胶系统为口腔黏膜再生提供了一种可临床转化的解决方案，通过其可调的物理化学性质和可控的治疗递送，满足了生物愈合需求和患者舒适度。
