Optimization of an O₂-balanced bioartificial pancreas for type 1 diabetes using statistical design of experiment

A bioartificial pancreas (BAP) encapsulating high pancreatic islets concentration is a promising alternative for type 1 diabetes therapy. However, the main limitation of this approach is O₂ supply, especially until graft neovascularization. Here, we described a methodology to design an optimal O₂-balanced BAP using statistical design of experiment (DoE). A full factorial DoE was first performed to screen two O₂-technologies on their ability to preserve pseudo-islet viability and function under hypoxia and normoxia. Then, response surface methodology was used to define the optimal O₂-carrier and islet seeding concentrations to maximize the number of viable pseudo-islets in the BAP containing an O₂-generator under hypoxia. Monitoring of viability, function and maturation of neonatal pig islets for 15 days in vitro demonstrated the efficiency of the optimal O₂-balanced BAP. The findings should allow the design of a more realistic BAP for humans with high islets concentration by maintaining the O₂ balance in the device.