Solvent environment modulates effects of glutaraldehyde crosslinking on tissue-derived biomaterials

Bioprosthetic materials utilized in the construction of heart valves and vascular grafts possess limited performance and viability in vivo. This is due (in part) to the failure of these materials to mimic the mechanical properties of the host tissue they replace. If bioprosthetic materials could be engineered to meet the mechanical performance required in vivo, the functional lifetime of implants would be increased. In this study, glutaraldehyde/solvent solutions of decreasing dielectric constant (polarity) were utilized to modify the properties of crosslinked collagen in whole bovine pericardial tissue. Solvents included phosphate buffer, methanol, 95% (w/w) ethanol, n-propanol, and n-butanol. Exogenous crosslinking was verified in collagen by thermal denaturation tests and amino acid analyses. Tensile mechanical behavior of collagenous pericardial samples was found to depend upon the dielectric constant (polarity) of the glutaraldehyde/solvent solutions employed; however, treatment in the solvents alone had little, if any, effect. As the dielectric constant of the solvents decreased, three mechanical properties were systematically altered: plastic strain fell from a mean of 8.9 +/- 1.5% (buffer) to 1.6 +/- 0.4% (n-butanol); strain at fracture increased from 32.2 +/- 2.6% (buffer) to 55.6 +/- 4.6% (n-butanol); and percent stress remaining after 1000-s stress relaxation from an 80-g initial load fell from 86.3 +/- 1.1% (buffer) to 76.9 +/- 1.0% (n-butanol). Crosslinking using a glutaraldehyde/n-butanol solution produced materials with tensile mechanical behavior that was very close to that of fresh tissue; however, the flexural properties of the treated tissue were different from those of fresh tissue. This decoupling of the flexural and tensile mechanical behaviors of crosslinked bioprosthetic materials is unique to this form of treatment. The observed phenomena may be the results of conformational changes in collagen facilitated by polar/nonpolar interactions with the solvent that are "locked in" by the action of glutaraldehyde. This technique may aid in the "customized" design of mechanical properties in tissue-derived biomaterials.