Carbon® University Program:
The TIDAL Model and Carbon DLS™ 3D Printing: A Dynamic Duo for Lung Health
By Catherine Fromen, Associate Professor in Chemical and Biomolecular Engineering, University of Delaware
“Spatial aerosol mimicry is made possible with 3D printing and lattice designs.”Catherine Fromen
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.
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?
“The TIDAL model is not just a lung replica; it’s a gateway to personalized treatments for respiratory diseases.”
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.
Figure 2. Interior lattice segments that go inside each lobe unit. Photo credit Ian Woodward
- Versatile Designs: What makes the TIDAL model exceptionally versatile is the ability to adapt various components to personalize the model to different individuals. This can be done by changing the upper airways, each of the lobe units, or by tuning the internal lattice designs. While our current TIDAL prototype is composed of two distinct lattice regions, the range of lattice design possibilities within the model is virtually limitless. This versatility allows our team to not only model personalized airway deposition but also to adapt the model to incorporate elements of lung diseases. Changing the lattice design especially offers a dynamic approach to explore different aspects of lung health and therapeutic interventions. For example, changing the internal lattice structure to be more closed in particular regions that map to obstructions in a patient CT scan could provide patient-specific heterogeneity that would better mimic disease progression.
With the TIDAL model in place, we can conduct a wide range of experiments to measure patient-specific airflows and lobe-specific spatial deposition assessments. By simulating various breathing patterns and disease states, we can assess where medicines from different inhalers end up in the lung. Performing these assessments over a range of medications, inhalers, and patient profiles, which can be easily achievable through the modular, plug-and-play components of TIDAL, we can gain a deeper understanding of how inhaled therapeutics work in different scenarios. This invaluable data will lead to more effective therapies for respiratory diseases.
Figure 3. Students working on TIDAL experiments in the lab. From left to right: Yinkui Yu (third-year PhD student) and Dr. Ian Woodward (Fromen lab alumnus and current postdoctoral researcher). Photo credit Catherine Fromen
In the realm of respiratory health and lung research, the future holds promising avenues for exploration. We anticipate further advancements in the development of tools, like the TIDAL model, that leverage Carbon DLS 3D printing and sophisticated anatomical modeling. These innovations will empower us to delve deeper into personalized therapies, refining our understanding of respiratory diseases and enhancing the effectiveness of inhaled therapeutics. Additionally, the ability to explore the vast landscape of lattice designs for intricate lung modeling will open doors to a more comprehensive study of lung diseases and tailored treatments. As we continue on this project with support from Carbon, the NSF, and NIH, the potential for better lung health and more effective respiratory solutions is on the horizon, offering hope for a brighter, healthier future enabled by 3D printing.
The TIDAL team at UD. From left to right: Yinkui Yu (third-year PhD student), Catherine Fromen (principal investigator), Dr. Ian Woodward (Fromen lab alumnus and current postdoctoral researcher). Photo credit: University of Delaware and photographer, Evan Krape
To learn more about Catherine Fromen’s work at University of Delaware and how her group is leveraging Carbon DLS technology, visit her website.