Ex vivo bioengineering of functional biomimetic airways for treatment of neonatal and pediatric respiratory conditions

用于治疗新生儿和儿童呼吸系统疾病的功能仿生气道离体生物工程

基本信息

批准号：
10371031
负责人：
CHRISTINE M FINCK
金额：
$ 24.77万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10371031
关键词：
3-Dimensional 3D Print Age Alginates Alveolar Biomedical Engineering Biomimetic Materials Biomimetics Bioreactors Bronchopulmonary Dysplasia Cell Adhesion Cell Survival Cell physiology Cells Characteristics Childhood Collaborations Collagen Complex Congenital Abnormality Cystic Fibrosis Dimensions Engineering Epithelial Epithelial Cells Excision Extracellular Matrix Formulation Future Gelatin Glycols Goals Growth Growth Factor Human Hydrogels Immunologics Joints Kinetics Laboratories Lung Mechanics Medical Imaging Natural regeneration Neonatal Patients Phenotype Physiological Play Polymers Population Printing Process Production Proteins Pulmonary Cystic Fibrosis Recording of previous events Resolution Source Structure Structure of parenchyma of lung Techniques Technology Testing Time Tissues Trachea Work airway epithelium base bioprinting cell growth cell growth regulation endodermal progenitor experience induced pluripotent stem cell innovation large print lung development lung injury novel pressure progenitor repaired respiratory scaffold stem stem cell differentiation stem cell growth stem cells

项目摘要

Project Summary Ex vivo engineering of functional respiratory tissues continues to be challenging. However, new bioengineering techniques are developing at a rapid pace. 3D bioprinting of trachea and large airways, incorporating both cells and biomimetic materials, is increasingly being applied for treatment of neonatal and pediatric respiratory conditions. Ideally, guided by medical imaging, a patient's own airway and/or alveolar stem/progenitor cells can be utilized to generate a novel patient-specific 3D-printed construct. However, biomimetic materials currently utilized in 3D bioprinting fail to recapitulate the complex microenvironment of the native lung and are not optimal for supporting lung stem/progenitor cell growth, differentiation, and function. Further, common biomimetic materials utilized do not grow as the patient ages. The objective of our proposal is to bioengineer a functional airway, through 3D printing technology, that mimics native medium and large airways in mechanical and compositional complexity. As extracellular matrix (ECM) has been shown to play an integral part in lung development and the regulation of cellular processes, our hypothesis is that decellularized ECM is an optimal substrate for 3D bioprinting of airway scaffolds and will promote growth, differentiation, and function of representative differentiated airway epithelial stem/progenitor cells. The following aims have been developed to test our hypothesis: Aim 1, mechanical optimization of human dECM 3D bioprinted airway structures; Aim 2, optimization of cell viability and phenotype in 3D bioprinted dECM airway structures. The significance of this proposal will be in demonstrating that dECM is an optimal substrate for not only the support and differentiation of functional airway epithelial cells, but also for the 3D printing of biomimetic airway tissues. The innovation of this proposal will be the optimization of this material for use in the production of functional implantable 3D printed neonatal and pediatric airway constructs to treat respiratory conditions such as Cystic Fibrosis, Bronchopulmonary Dysplasia and lung hypoplasia due to congenital defects.

项目概要功能性呼吸组织的离体工程仍然具有挑战性。然而，新生物工程技术正在快速发展。气管和大气道的 3D 生物打印，结合细胞和仿生材料，越来越多地应用于新生儿和儿童的治疗小儿呼吸系统疾病。理想情况下，以医学成像、患者自己的气道和/或肺泡为指导干/祖细胞可用于生成新型患者特异性 3D 打印结构。然而，目前用于3D生物打印的仿生材料无法重现复杂的微环境原生肺，对于支持肺干/祖细胞生长、分化和功能。此外，常用的仿生材料不会随着患者年龄的增长而增长。的目标我们的建议是通过 3D 打印技术模拟天然介质，对功能性气道进行生物工程设计以及大气道的机械和成分复杂性。由于细胞外基质 (ECM) 我们的假设显示其在肺部发育和细胞过程的调节中发挥着不可或缺的作用脱细胞ECM是气道支架3D生物打印的最佳基底，将促进代表性分化气道上皮干/祖细胞的生长、分化和功能。为了检验我们的假设，我们制定了以下目标：目标 1，人类的机械优化 dECM 3D 生物打印气道结构；目标 2，优化 3D 生物打印中的细胞活力和表型 dECM 气道结构。该提案的意义在于证明 dECM 是一种最佳选择基质不仅用于功能性气道上皮细胞的支持和分化，而且还用于 3D 仿生气道组织的打印。本提案的创新点在于对该材料的优化用于生产功能性可植入 3D 打印新生儿和儿童气道结构以治疗呼吸系统疾病，如囊性纤维化、支气管肺发育不良和肺发育不全先天性缺陷。