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

摘要

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.