Biocompatible Alginate Scaffolds Enabling Prolonged Hepatocyte Functions In Culture

Temporary hepatic support utilizing hepatocytes can save the life of patients suffering from liver failure since it can bridge the time needed for donor-patient matching in liver transplantation, and can in some cases give the time for liver regeneration without recurring to transplantation. Tissue engineering is one approach to achieve such supports. In this approach polymeric scaffolds play a critical role in maintaining the viability and functions of the hepatocytes.In this paper, a novel type of scaffold for hepatocyte culture and transplantation is reviewed. The scaffold consists of a sponge fabricated from alginates by a multistep technique that includes gelation, freezing and lyophilization. It has an appropriate porosity and pore size to accommodate a large cell mass and to allow blood vessel ingrowth after implantation; the pores are interconnected enabling the organization of the cells into a tissue; it has appropriate mechanical properties to assure flexibility and structure conservation; the matrix is bioresorbable and in addition is hydrophilic, thus facilitating cell seeding and distribution within the matrix. The hepatocytes seeded within the sponges are distributed homogeneously and are located mostly within the pores.The cells aggregate within the sponges until reaching a stationary size matching that of the pores at day 4 in culture. After 14 days in culture, the cell clusters appear as one particle. The hepatocytes maintain their biological function when grown as aggregates within the alginate sponges. Albumin secretion rates from hepatocytes seeded within the alginate sponges is considerably higher than those obtained for cells grown on standard collagen type I and continues for longer times. Urea synthesis by the hepatocytes immobilized in the alginate sponges remains relatively high at the end of 15 days. Studies are now in progress to evaluate these new cell constructs, in vivo.