Fabrication of homogeneously cross-linked, functional alginate microcapsules

A key engineering challenge in designing microcapsules made from biocompatible alginate is maintaining adequate exchange of nutrients and oxygen between the entrapped cells and the environment, while simultaneously avoiding swelling and subsequent failure of the microcapsule. Approval for the use of alginate in pharmaceutical and/or biomedical applications also strictly requires that the components of the microcapsule material must meet the safety criteria of the ASTM and FDA. Over the past two decades, a number of materials for preparing microcapsules have been investigated that alginate is one of the most promising polymers that may meet the microcapsule criteria for long-term functional immunoisolated cell transplantation. Gelation of alginate by external Ba2+ (or other divalent cations) produces non-homogeneous cross-linking of the polymeric mannuronic (M) and guluronic (G) acid chains. The stability of such microcapsules is rather limited. We will demonstrate that homogeneous cross-linking can be achieved by injection BaCl2 crystals into alginate droplets before they come into contact with external BaCl2. The high effectiveness of this crystal gun method is demonstrated by confocal laser scanning microscopy and by advanced nuclear magnetic resonance imaging. Encapsulation of rat islets, human monoclonal antibodies secreting hybridoma cells and murine mesenchymal stem cells transfected with cDNA encoding for bone morphogenetic protein (BMP-4) revealed that injection of BaCl2 crystals has no adverse side effects on cell viability and function. However, the release of low-molecular weight factors (such as insulin) may be delayed when using alginate concentrations in the usual range.