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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结