In vivo biocompatibility of dextran-based hydrogels

Abstract

Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over 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 blood 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 intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate 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 particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.

Biocatalytic synthesis of highly ordered degradable dextran-based hydrogels

“…The wound healing response to the implants consisted initially of macrophages eroding the hydrogel surface, fibroblasts depositing collagen into the region of the implant, and ARTICLE IN PRESS the presence of few foreign body giant (FBG) cells formed by fusion of macrophages, particularly in high DS dextran-DVA hydrogels. These tissue responses are consistent with those observed in other biocompatible hydrogel implants (e.g., crosslinked gelatin and methacrylated dextran hydrogels) [15,27].…”

“…3G) yielding little or no clear boundary between the hydrogel implant and the surrounding tissue. The lack of fully intact fibrous capsule formation is relatively unique in comparison to other non-degradable [14,15] and degradable [27,28] hydrogels, which favor the formation of fibrous capsule when implanted in vivo. This also compares favorably with other dextran-based hydrogels described elsewhere [29], where a continuous and compact fibrous capsule was observed after 4 weeks post-implantation.…”

“…This is particularly severe for hydrogels that contain a wide pore size distribution resulting in variable release profiles of large biomolecules and non-uniform materials properties leading to poor degradability [11,12]. Furthermore, in some cases, hydrogels may promote fibrous capsule formation upon implantation in vivo precluding their general use as scaffolds and implantable drug delivery systems [13][14][15].…”

Self-gelling hydrogels based on oppositely charged dextran microspheres

“…An organic solvent free approach to obtain crosslinked microspheres has been described where preparation occurs in an all-aqueous environment [18,19]. The in vivo biocompatibility of dextran-based hydrogels and microspheres has been demonstrated as well as the relation between in vitro and in vivo degradation behavior [20][21][22].…”

Scaffolds Based on Biopolymeric Foams

“…Polysaccharides [20,21] and gelatin [22] have already found widespread use in the preparation of matrices for biomedical applications.…”