Effect of alternative crosslinking methods on the low strain rate viscoelastic properties of bovine pericardial bioprosthetic material

Abstract

Early failures of bovine pericardial heart valves have been due to leaflet perforation/tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to the development of calcification, alternative crosslinking techniques have been suggested as means to overcome these obstacles. We have examined the low strain rate viscoelastic behavior of bovine pericardium: (1) fresh; (2) chemically treated with glutaraldehyde, cyanimide, or polyglycidyl ether; or (3) physically treated by freeze-drying or heat-drying. Shrinkage temperature tests were conducted to assess intrahelical crosslinking. Polyglycidyl ether and glutaraldehyde both produced substantial crosslinking, with the shrinkage temperature rising above 80 degrees C. Mechanical changes were nearly equivalent, both showing decreased stress relaxation and increased extensibility consistent with intrahelical crosslinking and shrinkage during fixation. Cyanimide, known to crosslink pure collagen materials, showed no evidence of crosslinking intact tissue. Heat-drying, also effective in pure collagen preparations, produced an increase in UTS and tissue modulus, but otherwise left the tissue unchanged. Freeze-drying had no mechanical effect, and therefore provides an attractive means for the storage of connective tissues for later mechanical testing.

Glutaraldehyde as a crosslinking agent for collagen-based biomaterials

“…Similar results have been reported for GA crosslinking of kangaroo tail tendon [27], lyophilized dermal sheep collagen [28] and pericardial tissue [29].…”

The role of collagen in the declining mechanical properties of aging human cortical bone

“…19 The technique has proved valuable in assessing the efficiency and density of artificially induced intermolecular crosslinks, produced by various chemical tanning agents, on a number of tissues. [20][21][22][23] The shrinkage temperature of cortical bone collagen has been shown to decline with age in rats 11 and in humans, healthy or otherwise. 4 A concomitant decrease in the biochemical stability of a tissue 4 implies that bone collagen becomes less stable with age.…”

Pericardial Processing: Challenges, Outcomes and Future Prospects

“…These alternative methods are used to bridge hydroxylysine residues of different polypeptide chains or amino groups of lysine by oligomeric or monomeric crosslinks (Sung et al, 2003). Because of the adverse effects of cross-linking with glutaraldehyde or other aldehyde treatments such as formaldehyde (Nimni et al, 1988) or dialdehyde starch (Rosenberg, 1978), numerous non-aldehyde treatments have been proposed, such as carbodiimides (Sung et al, 2003), glycerol (Ferrans et al, 1991), glycidal ethers (Thyagarajanet al, 1992) including poly(glycidylether) (Noishiki et al, 1986), acyl azide (Petite et al, 1990), cyanimide (Pereira et al, 1990), genipin (Wei et al, 2005), or dye-mediated photo-oxidation, phytate (Grases et al, 2008). Genipin, obtained from the fruits of Gardenia jasminoides ELLIS (Fujikawa et al, 1987;Tsai et al, 1994), exhibited better results than glutaraldehyde regarding its cytotoxicity (Sung et al, 1999), inflammatory response, ability to prevent calcification and tissue-induced mechanical properties (Wei et al, 2005 , 1989), was shown to be less cytotoxic, superior in pliability and to better inhibit calcification than glutaraldehyde (Sung et al, 1997).…”