The present invention provides methods for treating tissue to inhibit post-implant calcification of a biological tissue. In one method of this invention, a tissue is immersed in or otherwise contacted with a pretreated glutaraldehyde solution, i.e., a heat-treated or pH-adjusted glutaraldehyde solution. The tissue may be partially fixed with glutaraldehyde prior to, after, or concurrently with the step of contacting the tissue with the pretreated gluteraldehyde. Contact with the pretreated gluteraldehyde produces free amine groups on the tissue, which are subsequently blocked by contacting the crosslinked tissue with a blocking agent. In another embodiment, a tissue is contacted with either a non-pretreated glutaraldehyde or a pH-adjusted glutaraldehyde solution for a period of time sufficient to crosslink the tissue. The crosslinked tissue is then treated with a reducing agent that reduces aldehyde and carboxylic acid groups on the fixed tissue.

 
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