Islet-on-chip: promotion of islet health and function via encapsulation within a polymerizable fibrillar collagen scaffold.
Emma L VanderlaanJoshua SextonCarmella Evans-MolinaAdrian Buganza TepoleSherry L Voytik-HarbinPublished in: Lab on a chip (2023)
The protection and interrogation of pancreatic β-cell health and function ex vivo is a fundamental aspect of diabetes research, including mechanistic studies, evaluation of β-cell health modulators, and development and quality control of replacement β-cell populations. However, present-day islet culture formats, including traditional suspension culture as well as many recently developed microfluidic devices, suspend islets in a liquid microenvironment, disrupting mechanochemical signaling normally found in vivo and limiting β-cell viability and function in vitro . Herein, we present a novel three-dimensional (3D) microphysiological system (MPS) to extend islet health and function ex vivo by incorporating a polymerizable collagen scaffold to restore biophysical support and islet-collagen mechanobiological cues. Informed by computational models of gas and molecular transport relevant to β-cell physiology, a MPS configuration was down-selected based on simulated oxygen and nutrient delivery to collagen-encapsulated islets, and 3D-printing was applied as a readily accessible, low-cost rapid prototyping method. Recreating critical aspects of the in vivo microenvironment within the MPS via perfusion and islet-collagen interactions mitigated post-isolation ischemia and apoptosis in mouse islets over a 5-day period. In contrast, islets maintained in traditional suspension formats exhibited progressive hypoxic and apoptotic cores. Finally, dynamic glucose-stimulated insulin secretion measurements were performed on collagen-encapsulated mouse islets in the absence and presence of well-known chemical stressor thapsigargin using the MPS platform and compared to conventional protocols involving commercial perifusion machines. Overall, the MPS described here provides a user-friendly islet culture platform that not only supports long-term β-cell health and function but also enables multiparametric evaluations.
Keyphrases
- single cell
- healthcare
- public health
- cell therapy
- mental health
- tissue engineering
- high throughput
- stem cells
- low cost
- health information
- oxidative stress
- cell death
- cardiovascular disease
- magnetic resonance imaging
- quality control
- blood pressure
- mesenchymal stem cells
- small molecule
- magnetic resonance
- wound healing
- signaling pathway
- bone marrow
- endoplasmic reticulum stress
- circulating tumor cells
- ionic liquid
- carbon dioxide