In vivo biocompatibility of dextran-based hydrogels

Dextran-based hydrogels were obtained by polymerization of aqueous solution s of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-de rivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degrada ble dex-lactate-HEMA disk-shaped hydrogels, varying in initial water conten t and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated oa er a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new bl ood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and inter mediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous cap sule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degrad able dex-lactate-HEMA hydrogels was less severe compared with the dex-MA ge ls. In general, the size of the dex-lactate-HEMA hydrogels in-creased progr essively with time and finally the gels completely dissolved. Degradation o f the dex-lactate-HEMA hydrogels was associated with infiltration of macrop hages and the formation of giant cells, both of which phagocytosed pieces o f the hydrogel. A good correlation between the in vitro and the in vivo deg radation time was found. This suggests that extra-cellular degradation is n ot caused by enzymes but depends only on hydrolysis of the ester and/or car bonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particle s of the gels intracellularly. As for the dex-MA hydrogels, no toxic effect s on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatibl e materials, making these hydrogels attractive systems for drug delivery pu rposes. (C) 2000 John Wiley & Sons, Inc.