Submission
| Title: | Computational Modeling for Design of Next Generation Microphysiological Systems for Evaluation of β-Cell Health and Function |
| Co-Authors: |
Vanderlaan, Emma, Weldon School of Biomedical Engineering, College of Engineering, Purdue University, Medical Scientist/Engineer Training Program, Indiana University School of Medicine; Adrian Buganza Tepole, Weldon School of Biomedical Engineering, College of Engineering, School of Mechanical Engineering, College of Engineering, Purdue University; Sherry L. Voytik-Harbin, Weldon School of Biomedical Engineering, College of Engineering, Purdue University, Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University |
Abstract
Background/Significance/Rationale: Dynamic insulin secretion is a key focus of β-cell research, with microfluidic devices emerging as a potential means to effectively evaluate this performance parameter in-vitro. However, most devices maintain isolated islets in suspension despite evidence that collagen-islet interactions are critical to β-cell viability and function. When designing a microphysiological system with encapsulated islets, important considerations include 1) sufficient oxygenation, 2) rapid exchange of glucose and insulin between cells and perfusate, and 3) detectable levels of secreted insulin.
Methods: Computational models provide a means to simulate different device design parameters prior to fabrication, reducing the time and cost of testing multiple physical devices and microenvironmental conditions. For this study, COMSOL was used to model a microfluidic device containing islets macroencapsulated in a fibrillar collagen scaffold. A range of flow rates, collagen fibril densities, and islet-collagen construct dimensions were tested, with outcome measures including spatiotemporal changes in oxygen, glucose, and insulin.
Results/Findings: Simulations for all designs tested showed maintenance of islet viability as indicated by less than 1% of the construct area falling below the hypoxia-induced dysfunction threshold. Additionally, decreasing the construct thickness and increasing the medium glucose concentration yielded more rapid delivery of the target glucose stimulus to the islets, since glucose transport is primarily driven by diffusion within the construct. By contrast, transport of secreted insulin was found to be flow-limited and the presence of an encapsulation material altered the shape of the insulin secretion curve.
Conclusions/Discussion: Collectively, these results support the integrated use of computational models, together with experimental validation, as an efficient strategy for the creation of next generation microphysiological systems for evaluation of β-cell health and function.
Translational/Human Health Impact: A system that restores β-cells to a more physiological, pro-survival microenvironment and supports rapid functional assessments has the potential to improve the efficiency of preclinical studies.
