Poster 76 - Fabrication and Biomechanical Characterization of FRESH 3D-Bioprinted Tissue Engineered Vascular Grafts via an Open-source Pressure Myograph and Cardiac Flow Simulator, HemoLens

Saturday, October 26, 2024

10:00 AM - 12:00 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

LA

Liam Aranda-Michel (he/him/his)

Student Researcher
Lake Oswego Senior High School
Lake Oswego, Oregon, United States

Co-Author(s)

Antonio J. PereiraTavares

PhD Student
Department of Bioengineering, University of Pittsburgh
Pittsburgh, Pennsylvania, United States

Primary Investigator(s)

Daniel J. Shiwarski, PhD (he/him/his)

Assistant Professor
Department of Bioengineering, University of Pittsburgh Department of Medicine, Vascular Medicine Institute, University of Pittsburgh, Pennsylvania, United States

Introduction: Coronary Artery Disease (CAD) is the most common manifestation of cardiovascular disease, which is associated with millions of annual deaths. Coronary Artery Bypass Grafting (CABG) procedures are often necessary for revascularization of affected tissue in CAD, but existing grafts face challenges: autologous grafts are non-viable in one-third of CABG candidates, and synthetic grafts are often thrombogenic due to compliance mismatch and hydrophobicity. Tissue Engineered Vascular Grafts (TEVGs) aim to overcome these issues, but suffer lengthy development times, high cost, and are limited in patient specificity due to fabrication methods. Furthermore, tools used to mechanically assess TEVGs including industry-standard pressure myographs cost tens of thousands of dollars and are limited in throughput. Here, we synthesize and validate TEVGs via computational fluid dynamics, FRESH 3D-bioprinting vessel architecture from collagen-I, and development of an open-source, low cost pressure myograph and cardiac flow simulator to assess graft performance in in-vitro simulated hemodynamics. Results prove that mechanically robust TEVGs can be synthesized and validated for low-cost with an ECM-based bioink, custom geometry, and without complex or expensive manufacturing techniques.

Materials and

Methods: Architecture of the human Internal Thoracic Artery (ITA) was recapitulated in Autodesk Fusion 360, with added buffer geometry to facilitate suturing. Wall shear stress and flow profiles were assessed in a CFD-simulated cardiac cycle (Ansys Fluent) using the Carreau fluid model to emulate blood shear thinning. 5 TEVGs were Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinted from collagen-I (Advanced Biomatrix, 23mg/mL). “HemoLens”, an open-source pressure myograph and cardiac flow simulator, was designed in Autodesk Fusion 360 and built from 3D printed components and standard hardware (bolts, nuts, syringes, silicone tubing). Flow was achieved via a peristaltic pump and Arduino control, and pressure was applied via syringes to assess burst pressure. Graft distension was tracked via a USB camera and “Vasotracker, open-source imaging software.

Results, Conclusions, and Discussions: We validated graft architecture in CFD, bioprinted 5 collagen-I TEVGs, and developed an open-source platform to assess graft burst pressure and flow response. Grafts demonstrated uniform wall shear throughout the majority of the lumen, and a laminar velocity profile in CFD. Physical grafts were malleable and compliant, enabling suturing and manipulation. HemoLens, a low cost ( <$1000), open-source pressure myograph and flow simulator was developed. Using HemoLens, we demonstrated a linear relationship between TEVG diameter and velocity, and diameter and pressure, via two linear regression t-tests (R^2=0.91, p< 0.000065 & R^2=0.864, p< 0.000284 respectively), up to 115mL/min and 172.9mmHg. With HemoLens, we also proved an average burst pressure of 195.70mmHg (𝜎=7.24mmHg), higher than pressure typically experienced by the ITA in both normal and hypertensive patients. These results prove the feasibility of synthesizing and biomechanically validating robust, collagen-based TEVGs for low cost with open-source technology.

Acknowledgements (Optional): Many thanks to Dr. Daniel Shiwarski of the University of Pittsburgh for providing the grafts used in this research, and mentorship throughout the project. Thank you likewise to Antonio Pereira Tavares for assisting with bioprinting and project mentorship.

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