Statistical approach in alginate membrane formulation for cell encapsulation in a GMP-based cell factory.

A cell encapsulation technology in alginate has been developed with the aim of obtaining cell controlled release or three-dimensional cultures. The aim of this work is to verify the predictability of alginate capsules for large-scale production by Good Manufacturing Practice (GMP) standardized procedures in a cell factory. A cell-free capsule model was performed following the GMP guidelines: an opaque agent suspension in a bivalent cation solution (Ca(2+), Ba(2+), Sr(2+)) was dropped in a sodium alginate solution, obtaining capsules presenting a liquid core surrounded by a gel alginate membrane. The concentration of the ion, and the treatment with protamine, can considerably vary the characteristics of the capsules (weight, whole diameter, core diameter, gel capsule thickness, capsule strength). It is therefore possible to optimize the performance of the capsules, relating the molecular structure and size of the polymeric membrane to the desired functional properties. Technological resources are available for large-scale cell encapsulation intended for advanced therapies (gene therapy, somatic cell therapy and tissue engineering) in a cell factory, following GMP guidelines.