Application of AN69 hydrogel to islet encapsulation. Evaluation in streptozotocin-induced diabetic rat model.

The polymer AN69 (polyacrylonitrile-sodium methallylsulfonate) is a reference in biocompatibility in the field of hemodialysis. Its use for the encapsulation of living cells has been already described, but this study is the first description of AN69 hydrogel-encapsulated islet isograft in streptozotocin (STZ) diabetic rats. The aim of this work is to evaluate the biocompatibility of the AN69 hydrogel by comparison of the efficacy of free versus encapsulated islets transplanted to balance diabetes. Pancreatic islets are isolated from adult male Lewis rats by a standard collagenase digestion and purified on Ficoll density gradients. The AN69 hollow fiber is obtained by coextrusion of an 8% AN69 collodion. The hollow fiber is filled with islets suspended in agarose at the final concentration of 10,000 islets/ml, closed with surgical clips and implanted. The recipients are rendered diabetic by intravenous injection of STZ. The experimental design includes 4 groups of 8 rats: group 1: control, group 2: diabetic rats intraperitoneally implanted with 6000 free islets, group 3: diabetic rats intraperitoneally implanted with 9000 encapsulated islets, group 4: diabetic control. Weight and fasting glycemia are evaluated twice a week, diuresis once a week. After free islet implantation, rat survival is improved with glycemia below 250 mg/dl during 22 days. Compared to group 2, the status of group 3 is better, with a glycemia below 250 mg/dl during at least 70 days. This tends to demonstrate the biocompatibility of AN69 and is the first step of the validation of the use of AN69 for living cell encapsulation.

Preliminary report on cell encapsulation in a hydrogel made of a biocompatible material, AN69, for the development of a bioartificial pancreas.

The occurrence of an inflammatory reaction represents the major obstacle to the development of any implantable system including micro and macroencapsulation. The purpose of this study was to describe an encapsulation method for cells using a membrane made of AN69, a copolymer of acrylonitrile which is considered as a reference in biocompatibility in the field of haemodialysis. The hydrogel of AN69 was obtained after a coagulation step at room temperature followed by a solvent/non-solvent (water) exchange phase. Microcapsules were obtained by co-extrusion of AN69 collodion and saline (with or without cells). The function of encapsulated cells was assessed in vitro, demonstrating cell survival after the microencapsulation procedure. These preliminary data are consistent with the potential interest for the development of the microencapsulation procedure aimed at realising a bioartificial pancreas.