Prolonged Local Melatonin Delivery for Recurrent Laryngeal Nerve Neuropraxia

项目摘要/摘要： 本申请要求为对以下领域感兴趣的头颈外科医生颁发职业发展奖 喉返神经麻痹和发展局部治疗的延长方法。这个 所描述的职业发展计划将帮助她建立数据分析、研究设计和药物方面的技能 为成为独立的翻译研究人员开发局部疗法所必需的交付 耳鼻咽喉科应用。候选人的指导团队结合了神经科学的专业知识， 生物工程、喉科和耳鼻喉科提供协作环境，帮助她完成 她的目标。Kita博士在这个指导职业发展奖期间的目标是：1)完成课程 在生物统计学方法方面，2)发展缓释疗法的专业知识，以及3)设计一种方法 进一步描述Long Evans大鼠模型中神经性麻痹的恢复情况。 喉返神经的操作在颈部外科手术中是很常见的。 术后虚弱会导致说话、吞咽和呼吸困难。从返回函数 神经性麻痹是最轻微和最常见的神经损伤形式，通常需要几个月的时间。的减值 沟通、吞咽能力和呼吸会严重影响患者的生活质量。 这一次。这一奖项将允许候选人研究神经性麻痹的恢复和筛选局部干预措施。 因为他们有能力加快恢复。通过完成这个奖项，Kita博士将建立初步数据 以及一种可以用来测试治疗方法的神经性麻痹模型。这将通过三个目标来实现： 1.设计一种可持续洗脱的药物洗脱水凝胶。褪黑素将被包裹在聚(乳酸-co-丙交酯)中 羟基乙酸)纤维蛋白水凝胶中的微粒和药物洗脱的特征。 2.体外测定雪旺细胞对褪黑素的反应。雪旺细胞将在悬液中生长 褪黑素，过滤灭菌洗脱的褪黑素，和从水凝胶中的微粒分泌的褪黑素。 3.建立大鼠神经性麻痹后喉返神经恢复的动物模型。声乐 将使用折叠运动视频、肌电读数、超声波检查和免疫组织化学方法 描述Long-Evans大鼠模型的损伤后恢复情况。药物洗脱水凝胶将被植入并进行分析 因为他们有能力缩短声带运动在超声检查上的恢复时间。 摘要喉返神经麻痹是喉癌手术后常见且使人衰弱的并发症。 脖子。更好地描述这种伤害将使人们能够深入了解如何帮助处于危险中的个人。通过这件事 获奖候选人将研究一种延长局部治疗交付的方法，以表彰其帮助 手术后声带功能的恢复并建立成为一名 独立翻译研究员。

Project Summary/Abstract: This application requests a career development award for a head and neck surgeon with an interest in recurrent laryngeal nerve neuropraxia and developing prolonged methods of topical therapeutic delivery. The described career development plan will help her to build the skills in data analysis, study design, and drug delivery necessary to become an independent translational researcher developing topical therapeutics for Otolaryngology applications. The candidate’s mentorship team combines expertise from neuroscience, bioengineering, laryngology, and otolaryngology to provide a collaborative environment to help her accomplish her goals. Dr. Kita’s objectives during this mentored career development award will be: 1) Complete coursework in biostatistical methods, 2) Develop expertise in sustained-release therapeutics, and 3) Design a method of further characterizing recovery from neuropraxia in a Long Evans rat model. Manipulation of the recurrent laryngeal nerve is common in surgical procedures of the neck. Postoperative weakness can results in difficulty with speech, swallowing, and breathing. Return of function from neuropraxia, the mildest and most common form of nerve injury, often takes a few months. The impairment in communication, swallowing ability, and breathing that results can severely impact patient quality of life during this time. This award will allow the candidate to study recovery from neuropraxia and screen topical interventions for their ability to expedite recovery. Through the completion of this award, Dr. Kita will establish preliminary data and a model of neuropraxia that may be used to test therapeutics. This will be accomplished in 3 aims: 1. Design a drug-eluting hydrogel with sustained elution. Melatonin will be encapsulated in poly (lactic-co- glycolic acid) microparticles within fibrin hydrogels and elution of medication characterized. 2. Determine Schwann cell response to melatonin in vitro. Schwann cells will be grown with resuspended melatonin, filter-sterilized eluted melatonin, and with melatonin secreted from microparticles in hydrogels. 3. Create a rat model for characterizing recovery from recurrent laryngeal nerve after neuropraxia. Vocal fold movement video, electromyography readings, ultrasonography, and immunohistochemistry will be used to describe recovery after injury in a Long-Evans rat model. Drug-eluting hydrogels will be implanted and analyzed for their ability to shorten the period to recovery of vocal fold motion seen on ultrasonography. Recurrent laryngeal nerve neuropraxia is a common and debilitating complication after surgeries in the neck. Better characterization of this injury will allow insight into ways to help at risk individuals. Through this award the candidate will investigate a method of prolonged topical therapeutic delivery for its ability to assist in recovery of vocal fold function after surgical manipulation and establish the skills necessary to become an independent translational researcher.