title: Gelatin-based biomaterial engineering with anhydride-containing oligomeric cross-linkers.
abstract: Chemically cross-linked gelatin hydrogels are versatile cell-adhesive hydrogel materials that have been established for a variety of biomedical applications. The most prominent cross-linker is glutaraldehyde, which, however, has been described to cause compatibility problems and loss of microscopic but relevant structural features. A recently developed oligomeric cross-linker that contains anhydride functionalities was evaluated as cross-linker for the fabrication of gelatin-based hydrogels and microparticles. In a fast curing reaction, hydrogels composed of gelatin and oligomeric cross-linker were fabricated with good conversion over a wide concentration range of constituents and with cross-linkers of different anhydride contents. Hydrogel properties, such as dry weight and mechanics, could be controlled by hydrogel composition and rheological properties correlated to elastic moduli from 1 to 10 kPa. The gels were shown to be cytocompatible and promoted cell adhesion. In soft formulations, cells migrated into the hydrogel bulk. Gelatin microparticles prepared by a standard water-in-oil emulsion technique were also treated with the novel oligomers, and cross-linking degrees matching those obtained with glutaraldehyde were obtained. At the same time, fewer interparticular cross-links were observed. Fluorescein-derivatized cross-linkers yielded labeled microparticles in a concentration-dependent manner. The oligomeric cross-linkers are presented as an efficient and possibly more functional and compatible alternative to glutaraldehyde. The engineered hydrogel materials hold potential for various biomedical applications.
authors.affiliation: Institute of Pharmacy, Pharmaceutical Technology, Universität Leipzig , Eilenburger Strasse 15a, 04317 Leipzig, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Loth
authors.forename: Rudi
authors.initials: R
authors.lastname: Hötzel
authors.forename: Christian
authors.initials: C
authors.lastname: Kascholke
authors.forename: Ulf
authors.initials: U
authors.lastname: Anderegg
authors.forename: Michaela
authors.initials: M
authors.lastname: Schulz-Siegmund
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hacker
mesh_terms: D000812:Anhydrides / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002616:Chemical Engineering / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D005347:Fibroblasts; D005780:Gelatin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*
chemical_list: D000812:Anhydrides; D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D005780:Gelatin