Optimizing a patient-specific regenerative larynx implant for restoration of voice

摘要 喉支配着我们最基本的生命维持功能，是我们自我认同的基础。 即使是这个微妙而复杂的结构中最小的偏差也会导致生命的改变或生命的改变。 结束后果。呼吸、吞咽和发声的能力都是由喉调节的。即使 这些功能可以用各种管子和假肢来代替，它们不能代替正常的人。 体验.病人说，失去声音就像失去了自己的身份。他们想和自己的 再次发声，唱歌给他们的孩子，并与他们的家人一起吃饭。气管切开术中咳出粘液 管，通过胃管喂自己，像机器人一样说话都很尴尬，导致大多数人 过着与世隔绝的生活开发生物工程患者特定植入物可以恢复这三种功能 喉功能和改善愈合，从而挽救生命，提高生活质量。我们的目标 该项目是优化一个过程和一个产品，以恢复所有三个喉功能-呼吸，吞咽， 和声音--使用患者特定的固定半喉植入物，避免了翻修手术的需要， 改善愈合并增强植入物整合。为了实现我们的目标，我们将完成以下三个目标： 目的1：为了完善患者特定植入物形状的设计过程，我们将量化发声， 呼吸和用不同患者特异性植入物测试的切除喉的吞咽。目标2： 在没有肌肉瓣的情况下优化喉伤口愈合，我们将评估扁平支架补片， 在喉粘膜伤口的体内模型中的细胞和非细胞组分。目标3：评估 在长期的体内半喉重建模型中， 将评估免疫反应，组织整合，上皮发育和功能-发声，呼吸， 吞咽--使用具有最佳形状以及最佳细胞和非细胞的犬专用植入物 件.

Abstract The larynx governs our most basic life-sustaining functions and serves as the foundation of our self-identity. Even the most minor aberration within this delicate and complex structure can result in life-altering or life- ending consequences. The ability to breathe, swallow, and voice are all regulated by the larynx. Even though these functions can be replaced with various tubes and prosthetics, they cannot replace the normal human experience. Patients state that losing their voice feels like losing their identity. They wish to talk with their own voice again, sing to their children, and have a meal with their families. Coughing mucus out of a tracheostomy tube, feeding one’s self through a stomach tube, and speaking like a robot are embarrassing, leading most to live a life of social isolation. Development of a bioengineered patient-specific implant can restore all three laryngeal functions and improve healing, thereby saving lives and improving quality-of-life. The goal of our project is to optimize a process and a product to restore all three laryngeal functions -- breathing, swallowing, and voice -- with a patient-specific, immobile hemilarynx implant that obviates the need for revision surgery, improves healing, and enhances implant integration. To achieve our goal we will complete the following 3 aims: Aim 1: To refine the design process for a patient-specific implant shape, we will quantify voicing, breathing, and swallowing of excised larynges tested with different patient-specific implants. Aim 2: To optimize laryngeal wound healing without the muscle flap, we will evaluate flat scaffold patches with cellular and acellular components in an in vivo model of a laryngeal mucosal wound. Aim 3: To evaluate the performance of the bioengineered implant in a long-term in vivo hemilarynx reconstruction model, we will assess immune response, tissue integration, epithelial development, and function -- voicing, breathing, and swallowing -- with canine-specific implants with both optimal shape and optimal cellular and acellular components.