Osmotic pressure test: a simple, quantitative method to assess the mechanical stability of alginate microcapsules

Implantation of microencapsulated, nonautologous cells and tissues is an effective method to deliver therapeutic proteins in vivo. Its success depends on the maintenance of the immunoisolating barrier provided by the microcapsule. Thus, one goal in the development of this technology is to create mechanically stable microcapsules. We have developed an osmotic pressure test to quantify the strength of microcapsules by exposing alginate microcapsules to a graded series of hypotonic solutions and quantifying the percentage of broken microcapsules. The test was validated by confirming the relative strengths of different types of alginate capsules, previously known from implantation in dogs to have differing mechanical stability in vivo. Thus, solid alginate microcapsules crosslinked with Ba(2+) were shown to be stronger than those crosslinked with Ca(2+), which in turn were shown to be stronger than the corresponding hollow alginate microcapsules. The incorporation of cells was demonstrated to reduce the mechanical stability of the microcapsules significantly. Hence, this test provides a simple and quantitative method for rapidly determining the strength of a large number of microcapsules. Thus, it is suitable for monitoring the mechanical stability of various types of microcapsules, predicting the performance of microcapsules in vivo, and for quality control of microcapsules during scale-up productions.