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Two types of hydroxyethyl-methacrylated dextran (dex-HEMA) hydrogels differing in crosslink density were compared for local tissue responses and degradation characteristics in mice and rats. Implants (1 mm thick, rat: 10 mm diameter, mouse: 6 mm diameter) varying in degree of HEMA substitution (DS5 and DS13, meaning 5 or 13 HEMA groups per 100 glucose units of dextran) were subcutaneously implanted and tissue responses were evaluated at week 2, 6, and 13 after implantation. In the rat after 2 weeks a slight fibrous capsule was formed composed of macrophages and fibroblasts sometimes accompanied by a minimal infiltrate. Small fragments, surrounded by macrophages and giant cells indicated hydrogel degradation. After 13 weeks DS5 implants were resorbed while parts of the DS13 implants were still present. In the mouse a moderate to strong capsule formation was present at 2 weeks accompanied by inflammatory cells (macrophages and polymorphonuclear granulocytes) and debris. Draining lymph node activation was observed. Skin ulceration was present irrespective of the type of implant. Clear differences in the tissue responses between the rat and mouse were noted, as well as between implants of different degree of substitution. Mice showed a more pronounced early inflammatory response compared with rats, whereas the degradation was more complete in rats than in mice. The differences in histology between the hydrogels disappeared over time at 13 weeks after implantation and similar responses were noted for both types of hydrogels. Both in mice and rats the DS5 hydrogels showed a faster degradation rate than the DS13 hydrogels.

N-Carboxy-(N e -benzyloxycarbonyl)-L-lysine anhydride (Z-L-lysine NCA) was polymerized in dimethylformamide with triethylamine, diethylamine or hexylamine as initiator, at varying molar ratios of NCA to initiator (M/I ratio). After removal of the protecting Z-group the resulting poly-L-lysine was characterized with 'H NMR and MALDI TOF MS. Both diethylamine- and hexylamine-initiated polymerization yielded poly-L-lysine in which the initiators were incorporated at the carboxylic end of the polymer. This indicates that the NCA polymerization occurred exclusively via nucleophilic attack of the initiator on the monomer. On the other hand, when triethylamine was used as the initiator, poly-L-lysine was obtained in which no triethylamine-derived end group could be detected by MS. These polymer chains are most likely end-capped with an N-acyl-2,5-dioxopiperazine group at the carboxylic end of the polymer. Incorporation of diethylamine and hexylamine allowed determination of the degree of polymerization (DP) of the obtained polymers by 'H NMR. The DP depended linearly on the M/I ratio, for both diethylamine and hexylamine, with higher DPs for the diethylamine-initiated poly-l-lysine at equal M/I ratio.

Front Cover: Biodegradable nanogels based on polymers in which methacrylate groups were coupled to hydrophilic polymer backbones via biodegradable glycolate esters were developed. The obtained nanogels have tailorable degradation kinetics under physiological conditions by varying the structure of the polymers and crosslink density of the nanogels. The release of a loaded macromolecular model drug can be controlled upon the degradation of nanogels. Further details can be found in the article by Y. Chen, M. J. van Steenbergen, D. Li, J. B. van de Dikkenberg, T. Lammers, C. F. van Nostrum, J. M. Metselaar, W. E. Hennink on page 1122.