Optimal Tissue Engineering Approach for Treating Injured Vocal Folds

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。 ECM如果经过适当处理，可用作可吸收、临床安全和天然生物材料 促进组织重塑同时减少纤维化。可注射ECM水凝胶是临床应用的理想选择 和细胞交付，特别是考虑到正在出现的做法和独特的优势，在办公室程序使用 微创方法。我们小组和其他人的工作提供了关于 脱细胞声带固有层（VFLP-ECM）作为可注射剂或作为递送载体， 治疗细胞如间充质干细胞。我们广泛地假设VFLP-ECM水凝胶（具有或不具有VFLP-ECM水凝胶）是可降解的。 没有干细胞）将促进VF的功能性修复。

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. ECMs, if appropriately processed, can be used as resorbable, clinically safe, and naturally derived biomaterials that promote tissue remodeling while reducing fibrosis. Injectable ECM hydrogels are ideal for clinical application and cell delivery, 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 an injectable agent or as a delivery vehicle for therapeutic cells such as mesenchymal stem cells. We broadly hypothesize that VFLP-ECM hydrogels (with or without stem cells) will promote functional repair of the VFs.