title: Tissue response in the rat and the mouse to degradable dextran hydrogels.
abstract: 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.
authors.affiliation: Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. w.de.jong@rivm.nl
authors.forename: Wim H
authors.initials: WH
authors.lastname: De Jong
authors.forename: Jan A M A
authors.initials: JA
authors.lastname: Dormans
authors.forename: Mies J
authors.initials: MJ
authors.lastname: Van Steenbergen
authors.forename: Henny W
authors.initials: HW
authors.lastname: Verharen
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D003911:Dextrans / Q000378:metabolism*; D005549:Foreign-Body Reaction; D020100:Hydrogels / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology; D008422:Materials Testing; D008689:Methacrylates / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D019919:Prosthesis Implantation; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism
chemical_list: D003911:Dextrans; D020100:Hydrogels; D008689:Methacrylates; C508284:dextran hydroxyethyl methacrylate