INJECTABLE, TUNABLE THERAPEUTIC IMPLANT TO REDUCE VOCAL FOLD SCAR

可注射、可调节的治疗植入物可减少声带疤痕

• 批准号: 10647198
• 负责人: Gregory Robert Dion
• 金额: $ 24.11万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647198
• 关键词: Ablation; Absorbable Implants; Address; Adjuvant; Adjuvant Therapy; Adrenal Cortex Hormones; Affect; Benign; Biological Products; Biomechanics; Cell Therapy; Cicatrix; Clinical; Communication impairment; Data; Development; Dexamethasone; Dose; Drug Delivery Systems; Drug Implants; Dyes; Dysphonia; Effectiveness; Encapsulated; Extravasation; Eye; Fibrosis; Fluorescence; Foundations; Functional disorder; Glucocorticoids; Goals; Growth; Health Care Costs; Histologic; Histology; Immune response; Implant; Inflammation; Inflammatory; Injectable; Injections; Injury; Intervention; Intralesional Injections; Larynx; Lasers; Lesion; Light; Measures; Mechanics; Modeling; Mucous Membrane; Operative Surgical Procedures; Oral; Outcome; Patients; Persons; Pharmaceutical Preparations; Phonation; Postoperative Period; Pre-Clinical Model; Procedures; Property; Provider; Publishing; Quality of life; Repeat Surgery; Research; Small Interfering RNA; Speed; Structure; Submucosa; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Trauma; Treatment Cost; Treatment Efficacy; Voice; Voice Disorders; Wages; Work; biodegradable polymer; capsule; clinically relevant; cost; cyanine dye 5; design; digital imaging; drug release kinetics; effective therapy; healing; immunoreaction; implant design; implant material; improved; in vivo; injured; innovation; kinetic model; nanoparticle; novel; novel therapeutics; predictive modeling; repaired; response; side effect; treatment optimization; vibration; vocal cord; wound healing

Project Summary Vocal fold scarring results in voice dysfunction and decreased quality of life for patients. With around 20 million people impacted by voice disorders each year, and vocal fold scar a common cause of this dysphonia with few effective treatments available, new, novel treatment approaches are needed. Currently, one of the primary challenges to treatment is wound healing optimization in the dynamic, delicate vocal fold multi-layer structure. Although surgical repair can be employed for vocal fold scar treatment, current surgical techniques often result in subsequent scarring. Adjuvant local therapeutic delivery, most commonly with corticosteroids, is often used to improve wound healing; however, limited access to the vocal folds generally restricts providers to a single therapeutic injection at the time of surgery. In-office procedures exist for subsequent therapeutic vocal fold injections, though these are uncomfortable for patients and increase treatment costs. Oral corticosteroids are not an effective alternative, as research has found them less effective than local application and with more side effects. Additional novel biologics have been proposed for vocal fold scar treatment, though these are also limited by similar delivery problems to corticosteroids. We have found that a novel, injectable encapsulated implant can deliver corticosteroids over time either in a sustained release fashion or in a laser-light activated approach effectively for up to eight months in a leporine eye preclinical model. In prior work, we found minimal immune response or unanticipated drug leakage from the injectable implant in the leporine eye. In parallel, we have optimized vocal fold biomechanical quantification matched to histology after vocal fold injuries. In the first aim, we will optimize our injectable implant for the vocal folds and measure any local immune response in healthy leporine vocal folds. In the second aim, we will employ the implant in a vocal fold injury model to quantify its healing impacts compared to no treatment or traditional single corticosteroid injections. This work lays the foundation for optimized, dose controllable therapeutic delivery to the vocal folds and improved drug delivery.

项目摘要 声带疤痕会导致发音功能障碍，降低患者的生活质量。使用 每年约有2000万人受到嗓音障碍的影响，声带疤痕是一种常见的 这种发音困难的原因几乎没有有效的治疗方法，新的，新的治疗方法 我们需要一些方法。目前，治疗的主要挑战之一是伤口愈合。 优化了动感、细腻的声带多层结构。虽然手术修复 可用于声带疤痕的治疗，目前的手术技术往往会导致 随后会留下疤痕。辅助性局部治疗输送，最常见的是皮质类固醇 通常用于促进伤口愈合；然而，一般情况下，接触声带的机会有限 限制提供者在手术时只能注射一次治疗性药物。办公室内程序 存在于随后的治疗性声带注射中，尽管这些对 并增加了治疗成本。口服皮质类固醇不是有效的替代品，因为 研究发现，它们不如局部应用效果好，副作用更多。 其他新的生物制剂已经被提出用于声带疤痕的治疗，尽管这些是 也受到与皮质类固醇类似的给药问题的限制。我们发现了一部小说， 可注射包囊植入物可以随着时间的推移提供皮质类固醇，无论是持续的 以激光激活的方式或以激光激活的方法有效释放，最长可达八个月 Leporine眼部临床前模型。在之前的工作中，我们发现最低限度的免疫反应或 可注射植入物在眼内意外的药物泄漏。与此同时，我们有 优化的声带生物力学量化与声带损伤后的组织学相匹配。 在第一个目标中，我们将优化我们的声带注射植入物，并测量任何局部 健康麻风性声带的免疫反应。在第二个目标中，我们将使用植入物 在声带损伤模型中量化其与不治疗或不治疗的愈合影响 传统的单次皮质类固醇注射。这项工作为优化剂量奠定了基础。 可控制的声带治疗输送和改进的药物输送。