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.

项目概要 毁灭性的失声（发声困难或失声）影响着美国数千人 每年都进行外伤性或肿瘤性部分喉切除术或遭受肌肉损伤的国家 由于声带麻痹导致的音量损失。这些患者的声音恢复选择是 次优，因此，大多数患者会出现永久性的失声和沟通障碍 损害。该应用程序介绍了一种恢复声带肌肉体积的新方法 以及直接声带损伤和/或去神经支配后的功能。结果可能会导致改善 声带麻痹和/或接受过手术治疗的患者声音恢复的手术选择 半喉切除术、脊髓切除术或外伤性撕脱术。该应用程序的首要目标是 设计一种自体肌肉软骨植入物祖细胞衍生植入物（MI）， 植入动物模型，接受强大的神经支配，并在使用时发挥功能 修复大的喉部缺损。为此，我们将在定制的胶原蛋白中制造 MI 基质并用体外因子预处理 MI，诱导 MI 肌肉表达运动 端板。 MI 将用于替代猪模型中的部分喉切除术缺陷，以及 基于喉肌电图和量化的植入后神经支配状态 运动终板与神经接触，将被确定。使用这种动物植入模型， 研究 MI 的结果将与环境中的对照 MI 进行比较 无喉返神经完整性。拟议研究的结果应该克服 目前开发半喉功能性组织工程 MCC 的主要障碍 重建——这些障碍是软骨支持不足、神经支配不良 肌肉、肌纤维的次优组织以及肌肉的异步发射 原生内收肌。此外，由于这些研究现在正在大规模进行 动物（猪）模型，喉部大小和功能与人类非常相似，研究结果 将具有高度的转化性。这些实验的结果应该会带来具有里程碑意义的临床结果 与声音恢复应用和肌肉修复相关的创新 全球概念。