Computed Tomography-Guided 3D-Bioprinted Living Human Lung for Precision Medicine
Abstract
This proposal relates to Topic Areas “Lung Injury” and “Respiratory Health.” Critical Problem: Three of five leading causes of death in humans worldwide are lung-related, and the burden of lung disease in military personnel is heavy. For instance, respiratory infections, the most common cause of acute infectious disease in U.S. adults, are also the leading cause of outpatient illness and a major cause of infectious disease hospitalization in U.S. military personnel. Similarly, due to deployment-associated exposure, there has been an increasing prevalence of chronic lung diseases among Veterans. However, over the past several decades very few new classes of safe and effective therapies for lung diseases have been discovered. Another persistent challenge is the lack of reliable, specific, and sensitive biomarkers for early detection of various pulmonary conditions. These have been primarily attributed to overreliance of the scientific community on laboratory animals and conventional cell cultures. But mice are not humans, and animals often fail to accurately mimic human lung function at health and disease. Therefore, we need new technologies that faithfully replicate human diseases outside our body and allow us to accelerate discovery of new drugs and diagnostics. Innovation: Here, we propose a highly innovative and multidisciplinary approach that combines and employs latest discoveries in tissue engineering technologies called “Organ-on-a-Chip” and “3D-Bioprinting” to create “Next-Generation Bioartificial Lungs.” Applicability and Impact: This proposal is particularly important and timely as there now is a growing incidence of respiratory conditions in both active Service members and Veterans, who represent a significant health burden for the U.S. Army and the public. Development of “Personalized Bioartificial Human Lung,” as a substitute to conventional translational approaches, can greatly improve the medical care for military personnel by (1) replicating human organ-level lung physiology; (2) allowing investigation into mechanisms believed to be central to disease development; and (3) enabling accelerated drug development and diagnostic discovery. Moreover, our approach will yield a dual-purpose technological platform that can be used for both civilian and military aims. With a broad applicability, our engineered living lungs, for instance, can enable (1) modeling and identifying biomarkers of lung injury due to exposure to combat dust debris, desert dust, or sandstorms; (2) recreating clinically relevant models of lung fibrosis, asthma, or chronic obstructive pulmonary disease (COPD) to evaluate emerging therapies or repurpose existing treatments; (3) early detection of respiratory infections in deployed or training settings; and (4) as a medical countermeasure tool that may be used in the event of a potential public health emergency stemming from a terrorist attack with a biological, chemical, or radiological/nuclear material, or a naturally occurring emerging disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010035
Entities
People
- Kambez Benam
Organizations
- United States Army
- University of Colorado Denver