Tissue engineering to regenerate functional vocal fold after scarring or tissue loss

摘要 因创伤或喉癌而失去喉部声带覆盖物的患者 可能会有致残的声音困难，治疗选择有限。一种可植入的 振动替代组织将彻底改变喉部疾病的治疗。 该方案中描述的工作优化了基于细胞的外声带 由该实验室开发的替代物(COVR)在动物身上识别其功能 模型，并定义了其潜在的临床应用。分离的成人干细胞 从脂肪组织中培养出来，在纤维蛋白水凝胶中产生三维 适用于声带植入的组织替代物。 初步工作已经开发出COVR并将其植入兔体内，发现非常好 振动函数。这项工作计划对剩余的关键问题进行系统研究 做声带置换手术。宿主与移植细胞和基质的相互作用将是 已定义。将评估先前存在的疤痕环境和性别的影响。 将促进细胞外基质再生，并将力学行为量化。 拟议研究的成功完成将推动组织工程声乐的发展 向人工翻译靠拢。这项工作将定义合适的临床场景(现有 疤痕与新鲜组织切除)，最大限度地模仿正常声带的组织，以及 确定COVR促进声带伤口愈合的机制 控制。该提案中的动物研究将提供必要的信息 继续进行正式的临床前试验。

ABSTRACT Patients suffering loss of the larynx’s vocal fold cover due to trauma or laryngeal cancer can suffer disabling voice difficulties, and treatment options are limited. An implantable vibrating replacement tissue would revolutionize the treatment of laryngeal disorders. The work described in this proposal optimizes a Cell-based Outer Vocal fold Replacement (COVR) developed by this laboratory, identifies its functions in an animal model, and defines its potential clinical applications. Adult human stem cells isolated from adipose tissue are cultured within fibrin hydrogel to produce a three-dimensional tissue substitute suitable for vocal fold implantation. Preliminary work has developed and implanted the COVR in rabbits, finding excellent vibrational function. This work plans the systematic study of critical questions remaining for vocal fold replacement. Host interactions with implanted cells and matrix will be defined. Influence of pre-existing scar environment and sex will be assessed. Extracellular matrix regeneration will be promoted and mechanical behavior quantified. Successful completion of the proposed research will advance a tissue-engineered vocal fold towards human translation. This work will define suitable clinical scenarios (existing scar versus fresh tissue resection), maximize tissue mimicry of normal vocal folds, and identify mechanisms by which the COVR improves vocal fold wound healing relative to controls. The animal studies in this proposal will provide necessary information to proceed with formal pre-clinical trials.