Vocal cord tissue engineering: Pre-clinical scale-up

声带组织工程：临床前放大

基本信息

批准号：
10174851
负责人：
Jennifer L Long
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10174851
关键词：
3-Dimensional Adipose tissue Adult Adverse event Animal Model Animals Autologous Autopsy Canis familiaris Cells Chemicals Chronic Cicatrix Clinical Data Communication impairment Data Data Collection Deposition Development Emotional Endoscopy Evaluation Excision Extracellular Matrix Failure Family suidae Fatigue Fibrin Fibrosis Filler Gastroesophageal reflux disease Goals Grant Head and Neck Cancer Human Hydrogels Immunosuppression Impairment Implant Inflammation Inhalation Injury Intention Investigational New Drug Application Laboratories Laryngeal Diseases Larynx Malignant neoplasm of larynx Mammals Measures Methods Modeling Occupational Occupations Operative Surgical Procedures Oryctolagus cuniculus Outcome Outcome Measure Perioperative Perioperative Care Phonation Pilot Projects Postoperative Complications Postoperative Period Preparation Radiation therapy Recovery Regenerative Medicine Reproducibility Research Safety Smoke Social Interaction Steroids Structure Techniques Technology Time Tissue Engineering Tissue Grafts Tissues Translations Trauma Veterans Visual Voice Voice Disturbances Voice Quality Work base blood product experience healing immunosuppressed implantation improved improved functioning injured mesenchymal stromal cell multipotent cell phase I trial pre-clinical preclinical study preclinical trial pressure primary outcome repaired safety and feasibility scaffold scale up smoke inhalation social translation to humans vibration vocal cord vocalization wound wound healing

项目摘要

Veterans suffering loss of the larynx's vocal fold cover due to trauma or laryngeal cancer can suffer disabling voice difficulties, and treatment options are limited. A vibrating replacement tissue would revolutionize the treatment of laryngeal disorders. The work described in this proposal characterizes and optimizes a tissue-engineered Cell-based Outer Vocal cord Replacement (COVR). Adult human multipotent cells isolated from adipose tissue are cultured within fibrin hydrogel derived from the blood product cryoprecipitate. The result is a completely autologous three-dimensional tissue substitute. Upon implantation in rabbits, this construct healed well and produced normal short-term vibration for voicing. The COVR construct will now be introduced in a large animal model in preparation for human translation. This proposed research will assess the feasibility, safety, and efficacy of the tissue-engineered implant. Mechanisms of action will also be assessed by determining the fate of the implanted cells, and the effect on extracellular matrix and inflammation. Human cells will be implanted with immunosuppression. A canine model is planned because extensive prior laryngeal work has been performed in canines, providing ample data on normal phonation. If canines are impossible, a porcine model would also allow scale-up to large mammals and detailed study of the wound healing. Completion of the proposed research will determine whether the COVR meets safety and efficacy requirements to proceed with a larger trial. The goal is to restore normal voicing without adverse events. If successful outcomes occur in this pilot study, a larger trial will be performed with the intention of generating pre-clinical data for FDA application.

退伍军人因外伤或失去喉部声带覆盖喉癌可能会导致发声困难，治疗方案包括有限的。振动替代组织将彻底改变治疗喉部疾病。本提案中描述的工作具有以下特点：优化了基于细胞的组织工程外声带置换术（COVR）。从脂肪组织中分离出的成人多能细胞在源自血液制品冷沉淀物的纤维蛋白水凝胶。结果是完全自体三维组织替代物。植入后在兔子身上，这种结构愈合良好并产生了正常的短期振动发声。 COVR 构建体现在将被引入到大型动物模型中为人工翻译做准备。这项拟议的研究将评估组织工程植入物的可行性、安全性和有效性。机制还将通过确定植入细胞的命运来评估行动，以及对细胞外基质和炎症的影响。人体细胞将被植入与免疫抑制。计划制作犬类模型，因为之前进行了大量的研究已在犬科动物中进行了喉部工作，提供了正常情况下的充足数据发声。如果犬科动物不可能，猪模型也可以扩大规模对大型哺乳动物和伤口愈合的详细研究。拟议研究的完成将决定 COVR 是否满足安全性和有效性要求以进行更大规模的试验。目标是恢复正常发声而不会发生不良事件。如果成功的结果发生在在这项试点研究中，将进行更大规模的试验，目的是产生 FDA申请的临床前数据。