Alginate-cellulose sulphate-oligocation microcapsules: optimization of mass transport and mechanical properties.

Microcapsules based on polyelectrolyte complexation, where the inner phase involves a blend of alginate and sodium cellulose sulphate (SCS), have mechanical and transport properties which are relatively insensitive to the chemical composition of the rigid polyanion. Specifically, the bursting force of 400- and 1000 microm microcapsules increase slightly with the degree of substitution of the SCS, though the molar mass of the SCS appears to influence the transport properties more strongly than its composition. The concentration of the sodium chloride in the gelling batch can be varied rather extensively, with optimum properties at approximately half (i.e. 0.5 M) the level typically employed for the formation of cell-containing microcapsules. This indicates that the microcapsule properties can be tuned for biocompatability, without concern that changes to the polymer microstructure or reaction process conditions would adversely influence the bursting force or molar mass cut-off of the capsules. The alginate-SCS blend, which is typical equimass, can be slightly increased in favour of the SCS (to 55 wt%) if one seeks to mechanically optimize the system. The substitution of the oligocation polymethylene-co-guanidine with pDADMAC seems strongly undesirable. Similarly, the replacement of SCS with sulphoethylcellulose, while possible, offers no important advantages. The overall optimum conditions appear to be for a SCS with a DS of 2, prepared at 1.2 wt% of total cation with alginate. The ideal ratio, for mechanical and transport properties, of SCS to alginate is 55:45 (wt:wt), which represents a subtle modification from the classical formulation with very good biocompatability.

Objectively assessing bioartificial organs.

The metrics used, thus far, to assess bioartificial organ function are shown to be subjective and requiring validation. Therefore, four categories of correlations are proposed based on, respectively, device, in vitro and in vivo evaluations, and clinical function. Examples are presented whereby the correlations among individual indicators are used as a means to expedite the development of immunoisolated cells. Specifically, a case study illustrating the validation of in vitro indicators of in vivo graft function for the bioartificial pancreas (microencapsulated islets) is summarized. This has revealed thresholds with respect to given metrics relating to in vivo device function, the necessity to couple bioartificial organ design with transplant site selection, as well as the lack of objectivity involved in the evaluation and establishment of hypotheses. Specific quantitative indicators illustrate the need for quality-controlled measures, for example, relating to the tolerance of microcapsule diameter and membrane thickness distributions. Qualitative indices representing fibrosis and device properties (e.g., sphericity) are also used to describe the need for in vitro experiments in the development of bioartificial organs.

Development of cellulose sulfate-based polyelectrolyte complex microcapsules for medical applications.

Microencapsulation, as a tool for immunoisolation for allogenic or xenogenic implants, is a rapidly growing field. However most of the approaches are based on alginate/polylysine capsules, despite this system's obvious disadvantages such as its pyrogenicity. Here we report a different encapsulation system based on sodium cellulose sulfate and polydiallyldimethyl ammonium chloride for the encapsulation of mammalian cells. We have characterized this system regarding capsule formation, strength and size of the capsules as well as viability of the cells after encapsulation. In addition, we demonstrate the efficacy of these capsules as a "microfactory" in vitro and in vivo. Using encapsulated hybridoma cells we were able to demonstrate long-term release of antibodies up to four months in vivo. In another application we could show the therapeutic relevance of encapsulated genetically modified cells as an in vivo activation center for cytostatic drugs during tumor therapy.