Thermal Cross-Linking for Biologically Degradable Materials

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Abstract
To diminish undesirable side effects of chemical cross-linking of biodegradable materials, the authors developed a thermal cross-linking method that involved esterification by dehydration under dry conditions. The optimal condition for cross-linking was heating at 130-140 degrees C for 40 hr. Efficacy of the cross-linking was evaluated using enzymatic digestion of 0.01% protease in phosphate buffer at pH 7.4. Collagenous materials without cross-linking were digested completely within 30 min. However, with thermal cross-linking, it required 7 days for digestion. The capacity for holding onto water also was tested. Water content decreased when the cross-link density was increased. As an in vivo experiment, six succinylated collagen sealed vascular grafts treated with thermal cross-linking were implanted in the abdominal aortae of dogs and removed 21 days later. These grafts showed no foreign body reaction, and the collagen layer was almost completely absorbed. A collagen sealed graft cross-linked with formaldehyde used as a control showed a strong foreign body reaction. These results suggest that the physical cross-linking method was suitable for biodegradable biologicals, such as collagenous materials, without the undesirable side effects of chemical cross-linking regents.

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