An injectable, in situ enzymatically gellable, gelatin derivative for drug delivery and tissue engineering.
A phenolic hydroxyl group was incorporated into gelatin, using aqueous-phase carbodiimide activation chemistry, to obtain in situ gellable and injectable protein-based materials for drug delivery and tissue engineering applications. By this means, gelatin derivatives that were gellable via a peroxidase-catalyzed reaction were obtained. The enzymatically cross-linked gelatin gels did not melt at 37 degrees C and showed tunable proteolytic degradability. The time necessary for gelation decreased with increasing content of the phenolic hydroxyl (Ph) group, peroxidase concentration and decreasing H(2)O(2) concentration. Resistance to gel compression also depended on the content of Ph groups, with the gel containing the lowest Ph group content showing the greatest resistance to compression. We encapsulated L929 fibroblast cells in gelatin gels under conditions that induced gelation in about 10 s. The encapsulated cells showed about 95% viability. In addition, L929 cells seeded on the gels showed the same growth profiles as those seeded on an unmodified gelatin-coated dish. Subcutaneous rodent injection experiments demonstrated successful in situ formation of gels at the injected site.
Department of Chemical Engineering, Kyushu University, Motooka, Nishi-ku, Fukuoka, Japan. sakai@chem-eng.kyushu-u.ac.jp
Shinji
S
Sakai
Keisuke
K
Hirose
Kenichi
K
Taguchi
Yuko
Y
Ogushi
Koei
K
Kawakami
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002460:Cell Line; D016503:Drug Delivery Systems; D005780:Gelatin / Q000008:administration & dosage / Q000737:chemistry; D005782:Gels / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D015394:Molecular Structure; D016877:Oxidants / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D010636:Phenols / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D005782:Gels; D016877:Oxidants; D010636:Phenols; D005780:Gelatin; D006861:Hydrogen Peroxide; D010544:Peroxidases