An Accessible Platform to Quantify Oxygen Diffusion in Cell-Laden Hydrogels and Its Application to Alginate-Immobilized Pancreatic Beta Cells

Abstract

Hydrogels are commonly used to immobilize mammalian cells, offering mechanical support in 3D cultures and acting as barriers for immunoprotection in transplantation, such as islet encapsulation for diabetes therapy. Cell immobilization restricts bulk fluid motion, resulting in diffusion-limited molecular transport and nutrient concentration gradients, particularly for oxygen consumed by immobilized cells. Oxygen mass transport models are essential for designing immobilization strategies but often rely on assumed diffusion coefficients due to a lack of experimental data. We propose a cost-effective, accessible system for experimentally measuring oxygen diffusion coefficients in cell-laden hydrogels, tested on alginate-immobilized pancreatic beta cells (MIN6). Compared to water, oxygen diffusivity was significantly lower in alginate gels and inversely correlated with the dynamic loss modulus. Diffusivity also decreased with increasing alginate concentration from 2% to 5%. Cell viability depended heavily on gel concentration and cell density, as predicted by Thiele modulus and effectiveness factor values calculated from the measured diffusion coefficients. This platform, combining a simple experimental setup with dimensionless numbers, offers a practical way to predict maximal diffusion distances in cell immobilization strategies. The proposed approach can support rational design of cell encapsulation, immobilized cell culture, and tissue engineering strategies.