In vivo biodegradability and biocompatibility of porcine type I atelocollagen newly crosslinked by oxidized glycogen

Abstract

Oxidized glycogen is used as a collagen crosslinker to prepare materials with defined crosslinking rates. Thus, films are prepared from native or denatured porcine type I atelocollagen crosslinked with three crosslinking levels defined by the ratios between the aldehyde groups of the glycogen and the amino groups of the collagen. The remaining free aldehyde groups and the imine bonds formed in the reaction are subsequently reduced or not. All the materials are subjected to in vivo biocompatibility and biodegradability evaluations by subcutaneous implantation in mice, while immunogenicity is evaluated by rabbit immunizations. As a result, cellular reactions on the implantation site are more important with nonreduced materials, and biodegradability is correlated to the structural integrity of the collagen molecule, the crosslinking rate and the reduction state of the material. No immunological reaction or calcification is detected in our in vivo experimental model. This new method for collagen crosslinking using oxidized glycogen as a crosslinking agent enables the obtention of reproducible and biocompatible materials with a large scale of biodegradability, starting from 28 days to more than 7 months.