Augmenting Vocal Fold Repair Using an Optimized Lamina Propria Extracellular Matrix Derived Hydrogel

使用优化的固有层细胞外基质衍生水凝胶增强声带修复

• 批准号: 9926119
• 负责人: Donald O Freytes
• 金额: $ 57.4万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-04 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926119
• 关键词: Address; Affect; American; Anatomy; Architecture; Area; Biocompatible Materials; Biomechanics; Bladder; Cells; Cicatrix; Clinical; Communication impairment; Data; Derivation procedure; Detergents; Disease; Dysphonia; Engineering; Etiology; Extracellular Matrix; Fibroblasts; Fibrosis; Foundations; Gel; Goals; Human; Hydrogels; Impairment; In Situ; In Vitro; Injectable; Injury; Investigation; Laboratories; Lamina Propria; Link; Location; Mechanics; Methods; Modeling; Mucous Membrane; National Institute on Deafness and Other Communication Disorders; Oryctolagus cuniculus; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Performance; Physiology; Pliability; Pre-Clinical Model; Procedures; Process; Production; Property; Protocols documentation; Public Health; Reflux; Reporting; Research; Role; Small Intestinal Submucosa; Stimulus; Stomach; Strategic Planning; Structure; Symptoms; Testing; Therapeutic; Time; Tissues; Trauma; Treatment Cost; Voice; Voice Disorders; Wages; Work; biomaterial compatibility; biomaterial development; clinical application; clinical practice; cohort; experimental study; healing; iatrogenic injury; improved; in vivo; macrophage; minimally invasive; preclinical trial; repaired; response; scaffold; tissue repair; vocal cord; wound healing

PROJECT SUMMARY Voice impairment is the most common communication disorder with nearly 20 million people in the US reporting symptoms of dysphonia annually. The cost of treatment and lost wages for this disorder is approaching $13 billion. The etiology of these disorders is diverse, but given their anatomic location, the vocal folds (VFs) are susceptible to a multitude of injurious stimuli, including reflux of gastric contents, iatrogenic injury, and the inherent trauma associated with voice production. Injury can result in altered lamina propria (LP) architecture resulting in aberrant phonatory physiology. To date, no treatment restores the native VF extracellular matrix (ECM) composition, structure, and function following VF injury which likely underlies suboptimal outcomes for patients with VF scar. Extracellular matrix derived scaffolds, if appropriately processed, can be used as resorbable and naturally derived biomaterials with a safe record of clinical use that promote constructive tissue remodeling. Tissue- specific ECM hydrogels are ideal for clinical application, particularly given the emerging practice and distinct advantages of in-office procedures using minimally invasive approaches. Work from our group and others provide promising data regarding the role of decellularized vocal fold lamina propria (VFLP-ECM) as a therapeutic scaffold. We broadly hypothesize that VFLP-ECM will evolve into clinical practice to provide a scaffold that promotes functional repair of the VFs. Specifically, we seek to develop an injectable vocal fold lamina propria hydrogel (VFLP-ECMh) that will degrade over time while harnessing the stimulatory effects of the ECM to drive vocal fold tissue remodeling.

项目总结 语音障碍是最常见的沟通障碍，据美国近2000万人报告 每年都有发音困难的症状。这种疾病的治疗费用和工资损失接近13美元。 十亿美元。这些疾病的病因多种多样，但考虑到它们的解剖位置，声带皱折(VF)是 易受多种有害刺激的影响，包括胃内容物反流、医源性损伤和 与发声有关的固有创伤。损伤可导致固有层(LP)结构改变 导致异常的发音生理。到目前为止，还没有任何治疗方法能恢复天然的VF细胞外基质 室颤损伤后(ECM)的组成、结构和功能可能是导致VF预后不佳的基础 伴室颤疤痕的患者。 细胞外基质衍生的支架，如果经过适当的处理，可以作为可吸收的天然支架使用 具有安全临床使用记录的衍生生物材料，可促进建设性组织重塑。组织- 特定的ECM水凝胶是临床应用的理想选择，特别是考虑到新兴的实践和独特的 使用微创方法的办公室内程序的优势。我们小组和其他人的工作 提供关于脱细胞声带固有层(VFLP-ECM)作为 治疗性脚手架。我们广泛假设VFLP-ECM将演变为临床实践，以提供一种 促进VFS功能修复的支架。具体地说，我们寻求开发一种可注射的声带 固有层水凝胶(VFLP-ECMh)会随着时间的推移而降解，同时利用 ECM驱动声带组织重塑。