The TIDAL Model and Carbon DLS^™ 3D Printing: A Dynamic Duo for Lung Health

Introduction

Our lungs are our body’s vital gateways to the world, and maintaining their health is essential for overall well-being. However, treating respiratory diseases has long been plagued by inefficiencies, with most inhaled medicines following a “one-size-fits-all” approach. This approach overlooks the fact that every individual’s airways are not only complex but unique, which influences how medicines will flow through these airspaces. To create improved and personalized inhaled therapeutics that address a range of lung diseases, new tools that can predict how well an inhaled medication or vaccine will work in the lungs are needed.

In this pursuit of better lung health, our team at the University of Delaware has developed the “total inhalable deposition in an actuated lung” (TIDAL) model, uniquely enabled by Carbon Digital Light Synthesis™ (Carbon DLS™) 3D printing. This innovative approach focuses on creating an experimental testing tool that can precisely measure aerosol deposition within the lungs under realistic breathing conditions, offering the potential to change the way we understand and improve inhaled therapeutics. By providing tools like TIDAL that are capable of accurately measuring aerosol deposition in the lungs, we hope to usher in a new era of more effective, tailored, and personalized treatments for respiratory diseases, ensuring that each person receives the treatment that best suits their unique lung characteristics.

Research Challenge

The main challenge in advancing inhaled therapeutics is predicting how they will work. The complexity of the airway structure and motion, combined with the intricate physical phenomena of inhaled medicines, makes it nearly impossible to predict responses of inhaled medicines in the lung. Testing these new medications directly in humans carries unnecessary risk, which slows down the pace of medical research. A realistic model of the lung that could replicate the complex internal structures and breathing maneuvers to measure where the medicine ends up would allow researchers to test their new inhaled medications in a high-throughput manner and safely iterate over new formulations and inhaler designs.

Creating a useful replica of the lung is no small feat. 3D printing provides an important first pass to create patient-specific upper airways from CT scans. Yet these scans have limitations, because they can image only a small fraction of the entire airway structure. Thus, creating a model of the entire lung is a huge challenge. The lung’s architecture includes a vast network of bronchi and bronchioles, which continually branch into smaller and smaller airways, ultimately leading to the alveoli, or terminal region of the lung, where the exchange of oxygen and carbon dioxide occurs. The branching of the lung is highly complex, with varying diameters and lengths, which ends in an incredibly large number of tiny alveoli structures (over 500 million!). The total surface area alone is nothing short of staggering, equal to that of a tennis court! Thus, attempting to completely replicate this intricate complexity with traditional manufacturing methods is very far outside the realm of possibility.

So, the real research challenge becomes clear: how can we create a model that faithfully emulates the properties of the lung without physically replicating an entire organ?

Solution: The TIDAL Model

This is where innovative technologies, such as Carbon DLS 3D printing, have been truly enabling. Through our ability to rapidly prototype, our team has converged on a design for a new lung model that we have called “TIDAL.” The TIDAL (total inhalable deposition in an actuated lung) model boasts a sophisticated and intricate structure, designed to replicate the complexities of the human lung, to enable measurements of aerosol deposition as a function of patient-specific breathing, anatomy, and disease state. This innovative model is created through the power of Carbon DLS 3D printing, allowing for a level of precision and customization that was previously unattainable. Some of its key features are:

• Patient-Specific 3D Printed Upper Airway: At the heart of the TIDAL model is a highly detailed, patient-specific 3D printed airway. From the mouth to the first major bifurcations, the TIDAL airway is a faithful replica of an individual’s unique lung anatomy obtained directly from that patient’s CT scan. Using Carbon DLS technology, we can swap out different upper airways onto the TIDAL model, which are some of the biggest sources of interpatient-variability. This personalized aspect ensures that TIDAL can accurately mirror the specific characteristics of a patient’s respiratory system.
• Five Breathing-Lobe Units: The TIDAL model includes five lobe units, which are custom-designed to match each of the five anatomical lobes of an individual patient’s lung volumes. Each lobe unit also has independent motor control, allowing the end of each unit to move autonomously to replicate the inhalation and exhalation phases of the breathing cycle. The lobe units can execute dynamic respiratory maneuvers, mimicking various breathing patterns, rates, and depths. This dynamic flexibility provides a lifelike representation of the human respiratory system, enabling our team to assess how different breathing scenarios affect the deposition and effectiveness of inhaled therapeutics. The overall customization is crucial because lung volumes and breathing profiles can vary significantly from person to person.

Figure 1. The TIDAL model, fully assembled. Photo credit Ian Woodward

• Porous Lattices: Inside the lung lobes, the TIDAL model incorporates intricate porous lattices. These lattices are porous structures that can only be made through additive manufacturing. While lattices appear in many structural applications, our team is one of the first to use them as modular filters to collect aerosols out of the airstream. With their precisely tuned design, lattices serve the purpose of recreating the surface area and bifurcations found in the human lung to collect aerosols spatially throughout the lobe unit. Carbon DLS technology provides the capability to create lattices with extremely small features but overall large part sizes, ensuring that aerosols are collected in the right places to accurately replicate the lung’s characteristics.