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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：
8963014
负责人：
Stacey L. Halum
金额：
$ 45.29万
依托单位：
PURDUE UNIVERSITY
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 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8963014
关键词：
3-Dimensional Adipose tissue Adult Animal Model Animals Aphonia Autologous Cells Characteristics Clinical Collagen Collagen Fibril Communication impairment Cordectomy Data Defect Denervation Dysphonia Electromyography Engineering Environment Exhibits Expressed Emotion Fiber Goals Human Implant In Vitro Individual Injury Laryngeal Injury Laryngeal muscle structure Laryngectomy Larynx Lead Left Literature Malignant Neoplasms Methods Modeling Motion Motor Motor Endplate Muscle Muscle Fibers Muscle satellite cell Nerve Operative Surgical Procedures Organ Outcome Paralysed Patients Pattern Personality Polymers Positioning Attribute Rattus Recurrent Laryngeal Nerve Reporting Research Stem cells Surface Tissue Engineering Trauma United States Voice base density design engineering design experience functional restoration implantation improved in vivo innovation instrument nerve injury nerve supply neuromuscular novel novel strategies public health relevance reconstruction repaired research study restoration scaffold self assembly vocal cord

项目摘要

DESCRIPTION (provided by applicant): 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 develop a muscle progenitor cell-derived implant (MI) that, after implantation in an animal model, receives strong innervation. Specifically, the effect of myofiber motor endplate expression on post-implantation innervation of MIs will be determined. To do this, we will fabricate 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 syngeneic rat 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. The next goal of this application is to develop a MI within a customized collagen matrix, and determine if this approach will facilitate improved alignment of muscle fibers and enhanced muscle volume when used to repair laryngeal muscle defects. To reach these goals, MIs will be created with collagen polymers exhibiting self-assembly and hierarchical engineering design of collagen fibril matrices to guide cell fate, and thereby facilitating formation of muscle fibers wih size, myofiber density, and alignment that mimics the characteristics of the native vocal fold muscle. Again, using an animal model, outcomes with the collagen based 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 innervation of the muscle, suboptimal organization of myofibers, and asynchronous firing of the muscle with the native adductor muscle. Furthermore, results from these initial experiments should lead to landmark clinical innovations that will be relevant to both voice restoration applications, and muscle repair concepts globally.