Multilayer capsules: a promising microencapsulation system for transplantation of pancreatic islets

Abstract: In 1980, Lim and Sun introduced a microcapsule coated with an alginate/polylysine complex for encapsulation of pancreatic islets. Characteristic to this type of capsule is, that it consists of a plain membrane which is formed during a single procedural step. With such a simple process it is difficult to obtain instantly a membrane optimized with respect to all the properties requested for islet transplantation. To overcome these difficulties, it is recommended to build up the membrane in several consecutive steps, each optimized for a certain property. In this study, we have analysed such a multilayer microcapsule for the encapsulation of pancreatic islets. Therefore, empty and islet containing alginate beads were coated with alternating layers of polyethyleneimine, polyacrylacid or caboxymethylcellulose and alginate. By scanning electron microscopy the thickness of the covering multilayer-membrane was estimated to be less than 800 nm by comparison with an apparatus scale. Ellipsometric measurements showed that the membrane thickness is in the range of 145 nm. Neither the encapsulation procedure, nor the membrane-forming step did impede the stimulatory response of the islets. The encapsulation even lead to a significantly better stimulatory response of the encapsulated islets during week three and five of cell culture. Furthermore, the multilayer-membrane did not deteriorate the biocompatibility of the transplanted microcapsules, allowing an easy tuning of the molecular cut-off and the mechanical stability depending on the polycation–polyanion combination used. The multilayer membrane capsule has obvious advantages compared to a one-step encapsulation procedure. These beads guarantee a high biocompatibility, a precisely adjusted cut-off, an optimal insulin-response and high mechanical stability although the membrane is only 145 nm thick.

Authors: Stephan Schneider, Peter Johannes Feilen, Viola Slotty, Daniel Kampfner, Simon Preuss, Svend Berger, Jürgen Beyer and Rainer Pommersheim

Source: Biomaterials, Volume 22, Issue 14, 2001, Pages 1961-1970

1. Introduction
2. Methods and materials
2.1. Islet isolation
2.2. Materials for encapsulation
2.3. Preparation of empty capsules and capsules containing islets (Fig. 1)
2.4. Measurement of the mechanical stability
2.5. Measurement of capsule size and physical integrity
2.6. Permeability measurements
2.7. Preparation of films for ellipsometric measurements
2.8. Culture conditions and insulin secretion
2.9. Transplantation procedure
2.10. Histology
2.11. Quantification of fibrosis as a marker of biocompatibility
2.12. Statistical analysis
3. Results
3.1. Physical integrity of the membrane and in vivo stability assay
4. Discussion

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