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Abstract
Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.
Highlights
Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes
Cylindrical cell-laden hydrogel fibers are commonly designed from 350–1000 μm in diameter[24,25,26], and planar slabs, typically from 250–600 μm in thickness[8,13,14]
The SONIC scaffold was comprised of a hydrophobic fluoropolymer PVDF-HFP, and the internal continuous air channels were created by a phase separation process
Summary
Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. In the absence of supplemental O2 provision, theoretical analyses suggest that islets should be within a few hundred micrometers from the bloodstream in surrounding tissue to avoid hypoxia[19,20] Based on this design principle, the cell module of an encapsulation system should be exceedingly thin to support favorable oxygenation[12,21]. Cylindrical cell-laden hydrogel fibers are commonly designed from 350–1000 μm in diameter[24,25,26], and planar slabs (the geometry endowed with the lowest surface area to volume ratio), typically from 250–600 μm in thickness[8,13,14]
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