School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China; Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, School of Stomatology, Department of Prosthodontics, The Affiliated Stomatology Hospital, Southwest Medical University, Luzhou, Sichuan, China; Department of Periodontics & Oral Mucosal Diseases, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, Sichuan, China.
Institute of Biomaterials and Surface Engineering, Key Laboratory for Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, PR China.
Acta Biomater. 2024 Oct 1;187:98-109. doi: 10.1016/j.actbio.2024.08.038. Epub 2024 Aug 28.
Oral aphthous ulcers are common mucosal lesions that cause pain and discomfort. There are diverse biomaterials and drug treatments for oral ulcers used in both research and clinical settings. However, the complex oral environment often results in low adhesion and short drug retention times, which lead to poor drug availability and treatment outcomes. In this study, a mussel-inspired adhesive hydrogel was developed by grafting catechol onto hyaluronic acid (C-HA), and dopamine was added for oxidative pre-polymerization to form modified hyaluronic acid (M-HA), which remarkably increased the adhesion of the hydrogels. Then, M-HA was interpenetrated into the gelatin methacryloyl (GelMA) network. Chlorhexidine gluconate (CHG) was then incorporated into the hydrogel to enhance its availability and therapeutic effect through its sustained-release capability. The GelMA/M-HA hydrogel demonstrated strong adhesion to wet tissues, antibacterial and anti-inflammatory properties, and good biocompatibility. In both rat oral ulcers and infected wounds, the adhesive hydrogel significantly accelerated the healing of the ulcers and infected wounds. These results indicated that this adhesive hydrogel offers a promising new strategy for the treatment of oral ulcers in clinical practice. STATEMENT OF SIGNIFICANCE: Oral ulcers are a common and high-incidence mucosal condition that seriously affect people's daily lives, often making it difficult for patients to chew and speak. However, a dynamic oral environment with various types of bacteria influences drug availability and treatment effects in clinical settings. To address this challenge, an adhesive, mussel-inspired, drug-loaded hydrogel was constructed using natural macromolecules (hyaluronic acid and gelatin) with good biocompatibility. Chlorhexidine gluconate (CHG), with its broad-spectrum antibacterial activity, has been incorporated to synergistically promote oral ulcer healing. The splendid adhesion, antibacterial, and therapeutic effects of this hydrogel demonstrated a new strategy for treating oral ulcers.
口腔阿弗他溃疡是常见的黏膜病变，会引起疼痛和不适。在研究和临床环境中，有多种用于治疗口腔溃疡的生物材料和药物治疗方法。然而，复杂的口腔环境通常会导致低粘附性和短的药物滞留时间，从而导致药物可用性和治疗效果不佳。在这项研究中，通过将儿茶酚接枝到透明质酸（C-HA）上来制备受贻贝启发的粘附性水凝胶，并添加多巴胺进行氧化预聚合以形成改性透明质酸（M-HA），这显著增加了水凝胶的粘附性。然后，M-HA 被互穿到明胶甲基丙烯酰（GelMA）网络中。然后将葡萄糖酸氯己定（CHG）掺入水凝胶中，通过其持续释放能力提高其可用性和治疗效果。GelMA/M-HA 水凝胶对湿组织具有很强的粘附性，具有抗菌和抗炎特性，并且具有良好的生物相容性。在大鼠口腔溃疡和感染性伤口中，这种粘附性水凝胶显著加速了溃疡和感染性伤口的愈合。这些结果表明，这种粘附性水凝胶为临床实践中治疗口腔溃疡提供了一种有前途的新策略。 意义声明：口腔溃疡是一种常见且高发的黏膜疾病，严重影响人们的日常生活，常使患者难以咀嚼和说话。然而，具有各种类型细菌的动态口腔环境会影响临床环境中的药物可用性和治疗效果。为了解决这一挑战，使用具有良好生物相容性的天然大分子（透明质酸和明胶）构建了一种粘附性、受贻贝启发的、载药水凝胶。具有广谱抗菌活性的葡萄糖酸氯己定（CHG）已被纳入其中，以协同促进口腔溃疡愈合。这种水凝胶的出色粘附性、抗菌和治疗效果为治疗口腔溃疡提供了一种新策略。
