Biochemical changes and cytotoxicity associated with the degradation of polymeric glutaraldehyde derived crosslinks

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Abstract
The reversibility of glutaraldehyde crosslinks has been suggested as a reason for failure of long-term bioprosthetic implants. The stability of such crosslinks was investigated in tendons and model compounds. Small but cytotoxic levels of glutaraldehyde were still released from crosslinked tendons even after these tendons were extensively rinsed for up to 6 months. The toxic effect was evidenced by the death of fibroblasts surrounding a midsection piece of rinsed crosslinked tendon, while the end section pieces did not show toxic effects. The formation and stability of glutaraldehyde modified [14]-L-lysine derivatives were investigated. The polymerization of glutaraldehyde with amino compounds was initially fast but continued to proceed slowly for months. Degradation of high-molecular-weight soluble polymers was detected by gel filtration chromatography. Low-molecular-weight soluble materials were also released from insoluble products which were formed when high concentrations of glutaraldehyde and radioactive lysine were reacted. These chemical and biological studies suggest that local cytotoxicity of glutaraldehyde crosslinked bioprostheses may be due to unstable glutaraldehyde polymers that persist in the interstices of crosslinked tissues.