Oxygenation and function of endocrine bioartificial pancreatic tissue constructs under flow for preclinical...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Diabetes Research

Background:

• Islet transplantation shows promise for type 1 diabetes but faces challenges like graft loss and limited retrieval.
• Current methods struggle with oxygenation and insulin delivery in larger models, hindering clinical translation.
• Extra-hepatic sites and encapsulation aim to improve graft survival and safety.

Purpose of the Study:

• To introduce a versatile in vitro perfusion system for culturing and studying centimeter-scale artificial tissues for insulin-secreting cell delivery.
• To evaluate the system's utility with three distinct bioartificial endocrine pancreas (BAP) configurations.
• To assess oxygenation, cell viability, and glucose-responsive insulin secretion in BAP models.

Main Methods:

• Development of a versatile in vitro perfusion system accommodating various tissue geometries and oxygenation levels.
• Computational modeling of oxygen gradients and experimental validation using live/dead assays and time-lapse imaging.
• Culturing of BAP configurations under flow and static conditions, with at-line sampling for insulin secretion analysis.

Main Results:

• Computational oxygen profiles correlated with experimental viability gradients.
• Real-time monitoring of cell viability using fluorescence imaging in one BAP configuration.
• Successful culture of BAPs for up to 7 days with demonstrated glucose-responsive insulin secretion.

Conclusions:

• The developed perfusion system effectively supports the culture and functional assessment of centimeter-scale BAPs.
• This platform can aid in de-risking and optimizing artificial tissue designs for diabetes therapy.
• The system offers a valuable tool for preclinical evaluation prior to human clinical studies.