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

项目摘要 语音障碍是最常见的沟通障碍，在美国有近2000万人报告说， 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。 亿这些疾病的病因是多种多样的，但考虑到它们的解剖位置，声带（VF） 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 与发声有关的内在创伤损伤可导致固有层（LP）结构改变 导致异常的发声生理学。迄今为止，没有治疗恢复天然VF细胞外基质 (ECM)VF损伤后的组成、结构和功能，这可能是VF的次优结局的基础。 VF瘢痕患者。 细胞外基质衍生的支架，如果适当加工，可以用作可再吸收的和天然的支架。 衍生生物材料，具有促进建设性组织重塑的安全临床使用记录。组织- 特定的ECM水凝胶对于临床应用是理想的，特别是考虑到新兴的实践和独特的生物相容性， 使用微创方法的办公室程序的优点。我们团队和其他人的工作 提供了关于脱细胞声带固有层（VFLP-ECM）作为 治疗支架我们广泛假设VFLP-ECM将发展到临床实践中， 促进VF功能修复的支架。具体来说，我们寻求开发一种可注射的声带 固有层水凝胶（VFLP-ECMh），其将随着时间的推移而降解，同时利用 ECM驱动声带组织重塑。

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.