Muscle progenitor cell-based implants for dynamic laryngeal muscle reconstruction

用于动态喉肌重建的肌肉祖细胞植入物

• 批准号: 10238755
• 负责人: Stacey L. Halum
• 金额: $ 54.31万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10238755
• 关键词: Address; Adult; Animal Model; Animals; Aphonia; Autologous; Autopsy; Biomanufacturing; Biomedical Engineering; Biopsy; Cartilage; Chondrocytes; Chondrogenesis; Clinical; Collaborations; Collagen; Communication impairment; Contralateral; Cordectomy; Custom; Data; Defect; Denervation; Dysphonia; Electromyography; Engineering; Environment; Expressed Emotion; Fatty acid glycerol esters; Fiber; Goals; Human; Implant; In Vitro; Individual; Injury; Laryngeal Injury; Laryngeal muscle structure; Laryngectomy; Larynx; Lead; Left; Legal patent; Liquid substance; Local anesthesia; Maintenance; Malignant Neoplasms; Mechanics; Medial; Methods; Modeling; Molds; Motion; Motor; Motor Endplate; Muscle; Muscle satellite cell; Nerve; Operative Surgical Procedures; Outcome; Paralysed; Patients; Pattern; Personality; Physicians; Positioning Attribute; Property; Recurrent Laryngeal Nerve; Research Personnel; Rodent Model; Scientist; Structure; Testing; Time; Tissue Engineering; Trauma; United States; Vial device; Voice; adult stem cell; base; cartilaginous; experimental study; functional restoration; implantation; improved; in vivo; innovation; instrument; nerve injury; nerve supply; novel; novel strategies; porcine model; pressure; reconstruction; repaired; restoration; scaffold; scale up; stem cells; translational model; vocal cord

Project Summary Devastating voice loss (dysphonia or aphonia) impacts thousands of individuals in the United States each year undergoing traumatic or oncologic partial laryngectomies, or suffering muscle volume loss due to vocal fold paralysis. Voice restoration options for these patients are suboptimal, and, as a result, most patients are left with permanent voice loss and communication impairment. This application introduces a novel approach for restoring vocal fold muscle volume and function after direct vocal fold injury and/or denervation. Results may lead to improved surgical options for voice restoration in patients who have vocal paralysis and/or have undergone hemilaryngectomies, cordectomies, or traumatic avulsions. The first goal of this application is to engineer an autologous muscle-cartilage implant progenitor cell-derived implant (MI) that, after implantation in an animal model, receives strong innervation and becomes functional when used to repair a large laryngeal defect. To do this, we will fabricate MIs within a customized collagen matrix and pre-treat MIs with factors in vitro that induce the MI muscle to express motor endplates. The MIs will be used to replace a partial laryngectomy defect in a porcine model, and post-implantation innervation status, based on laryngeal electromyography and quantification of motor endplates with nerve contact, will be determined. Using this animal implant model, outcomes with the study MIs will be compared to those of control MIs in environments with and without recurrent laryngeal nerve integrity. Findings from the proposed studies should overcome current major hurdles to developing a functional tissue engineered MCC for hemilaryngeal reconstruction—those hurdles being inadequate cartilaginous support, poor innervation of the muscle, suboptimal organization of myofibers, and asynchronous firing of the muscle with the native adductor muscle. Furthermore, because these studies are being done now in a large animal (porcine) model, with laryngeal size and function very similar to that of humans, findings will be highly translational. Results from these experiments should lead to landmark clinical innovations that will be relevant to both voice restoration applications, and muscle repair concepts globally.

项目摘要 毁灭性的语音丧失（烦难或阿方症）会影响曼联成千上万的人 每年都经历创伤或肿瘤学的喉切除术或肌肉 声带瘫痪引起的体积损失。这些患者的语音修复选择是 次优，结果，大多数患者都会遭受永久性的语音丧失和沟通 损害。该应用程序介绍了一种恢复声带肌肉量的新方法 直接声折损伤和/或神经保护后的功能。结果可能会改善 进行声带瘫痪和/或经历过的患者语音恢复的手术选择 半核切除术，脐带切除术或创伤性撕脱。该应用程序的第一个目标是 工程师一种自体肌肉植入物祖细胞衍生的植入物（MI） 在动物模型中植入，接收强大的神经并在使用时起作用 为此，我们将在定制的胶原蛋白中捏造MIS 矩阵和预处理因体外因素而诱导MI肌肉表达运动的因素 终结。 MIS将用于替代猪模型中的部分喉切除术缺陷，并且 基于喉肌电图和数量的植入后神经植入神经状态 将确定具有神经接触的运动端板。使用此动物植入模型， 研究结果将与与控制和控制的结果相提并论 没有复发性喉神经完整性。拟议研究的发现应克服 目前为Hemilaryngeal开发功能性组织工程MCC的主要障碍 重建 - 那些障碍不足，软骨支撑不足，不良的神经支配 肌肉，肌纤维的次优组织以及对肌肉的异步射击 本地加法肌肉。此外，因为这些研究现在正在大型 动物（猪）模型，具有与人类非常相似的喉大小和功能 将被高度翻译。这些实验的结果应导致具有里程碑意义的临床 与语音恢复应用和肌肉修复有关的创新 全球概念。