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

项目总结

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.