Prolonged Local Melatonin Delivery for Recurrent Laryngeal Nerve Neuropraxia

项目概要/摘要： 此申请要求为头颈外科医生提供职业发展奖， 喉返神经神经失用症和发展长期的局部治疗方法。的 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 交付必要成为一个独立的翻译研究人员开发局部治疗， 耳鼻喉科应用。候选人的导师团队结合了神经科学， 生物工程，喉，耳鼻喉科提供了一个合作的环境，以帮助她完成 她的目标Kita博士在此指导职业发展奖期间的目标将是：1）完成课程 在生物统计学方法，2）开发持续释放疗法的专业知识，和3）设计一种方法， 进一步表征了LongEvans大鼠模型中神经失用症的恢复。 喉返神经的操作在颈部外科手术中很常见。 术后虚弱可导致言语、吞咽和呼吸困难。函数返回自 神经失用症是最温和和最常见的神经损伤形式，通常需要几个月的时间。减值损失 沟通，吞咽能力和呼吸，结果可能严重影响患者的生活质量， 这次该奖项将允许候选人研究神经失用症的恢复和筛选局部干预措施 他们加快恢复的能力通过这个奖项的完成，Kita博士将建立初步的数据， 以及可用于测试治疗方法的神经失用症模型。这将在三个目标中实现： 1.设计具有持续洗脱的药物洗脱水凝胶。褪黑激素将被封装在聚（乳酸-co- 乙醇酸）微粒的纤维蛋白水凝胶和药物洗脱的特征。 2.测定体外雪旺细胞对褪黑激素的反应。施旺细胞将在重悬 褪黑激素、过滤灭菌洗脱的褪黑激素以及从水凝胶中的微粒分泌的褪黑激素。 3.建立大鼠神经失用后喉返神经恢复的模型。声乐 褶皱运动视频、肌电图读数、超声检查和免疫组织化学将用于 描述了Long-Evans大鼠模型中损伤后的恢复。将植入药物洗脱水凝胶并进行分析 因为它们能够缩短超声波检查中观察到的声带运动恢复的时间。 喉返神经失用症是一种常见的和衰弱的手术后并发症， 脖子更好地描述这种损伤将有助于深入了解如何帮助处于危险中的个人。通过这个 授予候选人将研究一种长期局部治疗输送的方法，以帮助 手术操作后声带功能的恢复，并建立必要的技能，成为一个 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.