Methods adopted for Micro-capsule Formation

The most widely used procedure for micro-capsule formation involves the gelation of charged poly-electrolytes around the cell core. The popular alginate-L-polylysine micro-capsules, for example, are obtained in the following sequence:

1) The cells are embedded in alginate droplets with the aid of a droplet generator (air / liquid jet or an electrostatic generator);

2) The droplets are transformed into rigid beads by inducing cross-linking with calcium ions;

3) The beads are coated with polylysine and alginate, thereby forming the semi-permeable capsule; and

4) The alginate core is liquefied with a chelating agent.

Micro-capsules surrounding individual cells or clusters such as islets should be physically durable, smooth and spherical for optimal bio-compatibility. Smoothness is one factor, which, in addition to the interfacial composition, reduces tissue irritation, which decreases the probability of cell overgrowth on the capsule surface if aggregated tissue such as beta-cell clusters (beta cells transform blood glucose concentration stimuli into a regulated, pulsatile, insulin secretion) is employed. The capsules should be as small as possible in relation to the islet size to optimize nutrient ingress and hormone egress.

The poly-electrolyte complexation technique used to make alginate-polylysine capsules is advantageous since the capsules are formed under very mild conditions. A disadvantage, however, is the impurities and batch to batch irreproducibility of the alginate, a naturally derived polysaccharide.The high mannuronic acid content of alginate was shown to be responsible for fibrotic tissue response. Fibrosis was reduced and a more resistant micro-capsule was fabricated by decreasing the mannuronic acid level of the alginate at the expense of the guluronic acid content, although these conclusions have been questioned by some authors. Another disadvantage of alginate-polylysine micro-capsules is that the alginate-polylysine membrane, a weak polyelectrolyte complex, gives the micro-capsules relatively poor mechanical properties.

Local changes in pH or ionic concentration may have influence on the integrity of these microcapsules drastically.

Several different hydrogels have been investigated to determine the efficacy of encapsulation therapy as treatment for multiple diseases in a variety of animal models. For instance, alginate-polylysine-alginate micro-capsules have been employed to encapsulate islets and to reverse the effects of diabetes in rats and mice. The mild encapsulation procedure preserved the integrity of the islet’s secretory function with long term viability maintained. Modified alginate-polylysine micro-capsules, which are smaller and stronger than the previous versions, improved the survival of the xenographic tissue grafts. Coating alginate-polylysine capsules with a poly(ethylene glycol)hydrogel or incorporating monomethoxy poly(ethylene glycol) pendant chains to the polylysine polymer backbone has led to improved biocompatibility compared to unmodified capsules. In an attempt to simultaneously control biocompatibility and permeability, polymer blends have been selected that were optimal with respect to islet cytotoxicity (as measured by in vivo tests or) as well as thermodynamic (swelling / shrinking) and mechanical parameters.

Tags: Bio Technology, Bio Genetics, Bio Artificial organs

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