Automatic production of double coated alginate microcapsules: Analysis of the experimental parameters by design of experiments

This paper describes a design of experiments (DoE) approach, of an automatic procedure for the microencapsulation of isolated neonatal porcine islets (NPI). Monodisperse droplets were prepared by a vibrational nozzle, using an alginate/polyornithine encapsulation procedure, that has been developed and validated in our laboratory to encapsulate pancreatic islets. Different experimental parameters were considered such as: frequency of vibration, amplitude of vibration, polymer pumping rate and distance between the nozzle and the gelling bath. The produced calcium-alginate gel microbeads displayed an excellent morphology as well as a very narrow size distribution. The automatically produced microcapsules did not alter morphology and viability and functional properties of the enveloped NPI. The optimization of this automatic procedure may provide a novel approach to obtain a large number of batches possibly suitable for large scale production of immunoisolated NPI for in vivo cell transplantation procedures in humans.