PERMEABILITY AND BIOCOMPATIBILITY OF A NEW HYDROGEL USED FOR ENCAPSULATION OF HEPATOCYTES

A new high-water-content (83%) and highly permeable anionic polyelectr olyte hydrogel was obtained by phase inversion of a polymer solution c ontaining 6% polyacrylonitrile-sodium methallylsulphonate, 91% dimethy lsulphoxide and 3% physiological saline solution. Hydrogel-based hollo w fibres (HFs) were fabricated with a co-extrusion apparatus in collab oration with Hospal (France). HFs have an internal diameter of 800 mu m and a wall thickness of 100 mu m. Experimental results demonstrated that hydrogel-based HFs were permeable to albumin (mel, wt 69 000) and human immunoglobulin G (150 000), but were impermeable to immunoglobu lins A (170 000) and M (900 000) after 24h of diffusion. In vitro, the viability of isolated rat hepatocytes injected into the HFs was 64 +/ - 6% after 10d versus 30 +/- 5% for hepatocytes cultured in Petri dish es (P = 0.0001). Under these conditions, the amount of albumin release d by encapsulated hepatocytes was 12 +/- 3 mu g/24h/10(6) cells at day 10, whereas at that time no albumin was released by hepatocytes cultu red in Petri dishes. In vivo, histological study of hydrogel HFs impla nted up to 6 wk in the peritoneum of rats revealed a low inflammatory tissue reaction without giant multinucleate cells in the foreign tissu e, which decreased after the third week. The survival rate of encapsul ated hepatocytes was over 85% 45d after transplantation in the periton eum of syngeneic Lewis rats. Therefore, this hydrogel demonstrates hig hly favourable properties for encapsulation of hepatocytes with regard to its biocompatibility, permeability and ability to maintain hepatoc ytes in a functional state for prolonged periods.