Dimethyl 3,3'-dithiobispropionimidate: a novel crosslinking reagent for collagen

Crosslinking agents are used for improving the physical properties and durability of collagenous implants, glutaraldehyde (GTA) being the most widely used. Many of these reagents, including GTA, are known to be cytotoxic and to induce calcification. Hence, it is desirable to develop new crosslinking methods for collagen, so that biocompatibility and physical properties are improved. In the present study, dimethyl 3,3' -dithiobispropionimidate (DTBP) has been tried as a novel crosslinking reagent for collagen. Collagen purified from rat tail tendon has been crosslinked with DTBP and GTA. An increase of 22 degrees C in shrinkage temperature is observed for collagen treated with DTBP under optimal conditions. Crosslinking density determination shows that DTBP induces 10 crosslinks per mole, compared to 13 by GTA. While the tensile strength of GTA-treated samples is greater than those treated with DTBP, the latter shows more extensibility. In vitro degradation studies show that both GTA- and DTBP-treated samples are resistant to degradation by collagenase. The biocompatibility of crosslinked collagen samples studied by subcutaneous implantation in rats show that while both GTA- and DTBP-treated collagen do not degrade for up to 4 weeks, ultrastructural and histological studies indicate that DTBP collagen is far more biocompatible than GTA-treated matrices.