Vascularized pancreas-on-a-chip device produced using a printable simulated extracellular matrix

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• The extracellular matrix (ECM) plays a critical role in cellular behavior and fate, yet its specific influence on pancreatic beta-cell development and maturation remains underexplored.
• Investigating the pancreatic islet's microenvironment is crucial for understanding beta-cell function and dysfunction in diseases like diabetes.

Purpose of the Study:

• To develop and evaluate a novel simulated extracellular matrix (sECM) for pancreatic beta-cell culture and research.
• To assess the impact of a functionalized bacterial cellulose-based sECM (sECMbc) on beta-cell function, including sprouting, insulin secretion, and gene expression.
• To validate the utility of a pancreas-on-a-chip device incorporating the sECMbc for drug screening and personalized medicine applications.

Main Methods:

• Formulation and characterization of various simulated ECM (sECM) hydrogels, including a promising combination with functionalized bacterial cellulose (sECMbc).
• Evaluation of cell viability, sprouting, insulin secretion, and gene expression (VEGF-A, Endothelin-1, NOS3) in response to different sECM formulations using a hydrogel-based, perfusable pancreas-on-a-chip device.
• Testing the sECMbc-integrated device with Sunitinib for drug screening and assessing its functionality in a seven-day dynamic culture.

Main Results:

• The sECMbc formulation, containing fibrin, collagen type I, Matrigel®, hyaluronic acid, methylcellulose, and bacterial cellulose, demonstrated superior performance compared to a fibrin-only matrix (sECMf).
• sECMbc significantly enhanced beta-cell sprouting (2-4x higher), insulin secretion (2-4x higher), and expression of key genes (VEGF-A, Endothelin-1, NOS3; 2-10x higher) without impacting cell viability.
• The pancreas-on-a-chip device with sECMbc proved functional in dynamic culture for seven days, suitable as a physiological model, and demonstrated 3D bioprintability.

Conclusions:

• A novel bacterial cellulose-based simulated extracellular matrix (sECMbc) effectively supports and enhances pancreatic beta-cell function in a pancreas-on-a-chip model.
• The developed sECMbc and device platform show significant potential for advancing diabetes research, drug screening, and personalized medicine approaches.
• The 3D bioprintable and perfusable nature of the device highlights its versatility for creating complex physiological tissue models.