Wa. Naimark et al., HMDC CROSS-LINKING OF BOVINE PERICARDIAL TISSUE - A POTENTIAL ROLE OFTHE SOLVENT ENVIRONMENT IN THE DESIGN OF BIOPROSTHETIC MATERIALS, Journal of materials science. Materials in medicine, 6(4), 1995, pp. 235-241
The need for alternative crosslinking techniques in the processing of
bioprosthetic materials is widely recognized. While glutaraldehyde rem
ains the most commonly used crosslinking agent in biomaterial applicat
ions there is increasing concern as to its biocompatibility-principall
y due to its association with enhanced calcification, cytotoxicity, an
d undesirable changes in the mechanical properties of bioprosthetic ma
terials. Hexamethylene diisocyanate (HMDC), like glutaraldehyde, is a
bifunctional molecule which covalently bonds with amino groups of lysi
ne residues to form covalent crosslinks. Evidence within the literatur
e indicates HMDC-treated materials are less cytotoxic than glutaraldeh
yde-treated materials; however, there is limited characterization of t
he material properties of HMDC-treated tissue. This study uses a multi
-disciplined approach to characterize the mechanical, thermal, and bio
chemical properties of HMDC-treated bovine pericardial tissue. Further
, to facilitate stabilization of the HMDC reagent, non-aqueous solvent
environments were investigated. HMDC treatment produced changes in me
chanical properties, denaturation temperature, and enzymatic resistanc
e consistent with crosslinking similar to that seen in glutaraldehyde
treated tissue. The significantly lower extensibility and stiffness ob
served under low stresses may be attributed to the effect of the 2-pro
panol solvent environment during crosslinking. While the overall accep
tability of HMDC as a crosslinking agent for biomaterial applications
remains unclear, it appears to be an interesting alternative to glutar
aldehyde with many similar features.