关键词: Antifibrotic Gellan Gum Microgel Pirfenidone Tissue Adhesive Vocal Fold

Mesh : Vocal Cords / pathology drug effects Tissue Adhesives / chemistry pharmacology Biocompatible Materials / chemistry pharmacology Cicatrix / drug therapy pathology Humans Materials Testing Cell Proliferation / drug effects Particle Size Microgels / chemistry Antifibrotic Agents / chemistry pharmacology Fibroblasts / drug effects Hydrogels / chemistry pharmacology Alginates / chemistry Cell Movement / drug effects Polysaccharides, Bacterial Pyridones

来  源:   DOI:10.1021/acsabm.4c00422

Abstract:
Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient\'s quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.
摘要:
声带(VF)疤痕,喉科的一个复杂问题,VFs分层结构的损伤和炎症的结果。由此产生的声音嘶哑,目前成功的治疗选择有限,影响患者的生活质量。逆转这种疾病的有希望的策略是使用抗纤维化药物。本研究提出了一种新型的微珠嵌入的可注射水凝胶,可以维持抗纤维化药物吡非尼酮(PFD)的释放,用于声带瘢痕形成。微珠是使用海藻酸钠和明胶开发的,将其进一步嵌入仿生和组织粘合剂结冷胶(GG)水凝胶中。嵌入微珠的水凝胶显示出改善的可注射性,粘弹性,组织粘附性,降解性,与没有珠子的水凝胶相比和溶胀。此外,嵌入珠子的水凝胶可以维持PFD的释放一周。体外研究表明,载药水凝胶可以剂量依赖的方式降低成纤维细胞的迁移和增殖。总之,这项研究证明了负载PFD的可注射水凝胶具有增强的粘弹性和组织粘附性,可用于声带瘢痕化应用的潜力。
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