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

摘要 喉支配着我们最基本的维持生命的功能，是我们自我认同的基础。 在这种微妙而复杂的结构中，即使是最微小的偏差也可能导致改变生活或生活- 结束后果。呼吸、吞咽和发声的能力都是由喉部控制的。即使 这些功能可以用各种管子和假体替代，它们不能取代正常的人类 经验。患者表示，失去声音就像失去了自己的身份。他们想和他们自己的人谈谈 再次发声，给他们的孩子唱歌，和他们的家人一起吃饭。从气管切开术中咳出粘液 管子，用胃管喂自己，像机器人一样说话都令人尴尬，导致大多数人 过着与世隔绝的生活。开发一种针对患者的生物工程植入物可以修复这三种情况 喉部功能和改善愈合，从而挽救生命和提高生活质量。我们的目标是 项目是优化一种工艺和一种产品，以恢复所有三种喉部功能--呼吸、吞咽、 和声音--通过患者专用的、固定的半喉植入物，消除了翻修手术的需要， 改善愈合，增强植入物的整合性。为实现我们的目标，我们将完成以下三个目标： 目标1：为了改进特定于患者的种植体形状的设计过程，我们将量化发声， 呼吸和吞咽切除的喉咙，用不同的患者特定的植入物进行测试。目标2：实现 在没有肌瓣的情况下优化喉部伤口的愈合，我们将用以下方法评估扁平支架贴片 喉粘膜损伤活体模型中的细胞和非细胞成分。目标3：评估 生物工程植入物在长期活体半喉重建模型中的性能 将评估免疫反应、组织整合、上皮发育和功能--发声、呼吸和 吞咽--犬类专用植入物，具有最佳形状和最佳细胞和非细胞 组件。

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.