In vitro biocompatibility of biodegradable dextran-based hydrogels tested with human fibroblasts

The cytotoxicity of dextran T40, methacrylated dextran (dex-MA) and hydroxy ethyl-methacrylated dextran (dex-HEMA), dextran-based hydrogel discs and mi crospheres, and their degradation products, was studied by measuring the ce ll proliferation inhibition index (CPII) on human fibroblasts in vitro. In addition, during the 72h incubation period light-microscopic observations w ere performed daily. After 24h of incubation with dextran and dex-HEMA poly mers, the cells showed elongated or spider-like forms, some lipid droplets and intracellular granula, indicative of pinocytosis and internalization of the polymers. During the next two days, the fibroblasts' appearance did no t change. Methacrylic acid (MAA), formed by hydrolysis of dex-HEMA, did not influence the cell morphology. Dex-HEMA polymer solutions with a low and h igh degree of substitution (DS) at 100 mg/ml caused a CPII of 30-40% after 72 h. This is less than 10% growth inhibition per cell cycle and statistica lly not different from the CPII induced by 100 mg;ml dextran T40. Growth in hibition induced by MAA was also low. The various dex-MA hydrogel discs cau sed similar low growth inhibition. Interestingly, hydrogel microspheres of dex-MA and dex-(lactate)HEMA caused a CPII of only 0-20% after 72 h. The re sults presented in this study demonstrate that methacrylate-derivatized dex tran hydrogels show good biocompatibility in vitro making these degradable biomaterials promising systems for drug delivery purposes. (C) 2001 Elsevie r Science Ltd. All rights reserved.