Methods for treating a bioprosthetic tissue are described. The methods comprise contacting the biological tissue with an anchor compound, the anchor compound comprising first and second functional groups. The first functional group is reactive with and couples a tissue functional group associated with the biological tissue. The second functional group is one of a bio-orthogonal binding pair. The biological tissue coupled to the anchor compound is then exposed to a linking compound. The linking compound comprises at least two functional groups, each comprising the other one of the bio-orthogonal binding pair. In a preferred embodiment, the bio-orthogonal binding pair is an azide and an acetylene. The method can be performed in the presence of a catalyst, preferably a copper catalyst. Alternatively, the method can be performed in the absence of a catalyst, wherein the acetylene is incorporated in a ring-strained cyclic compound, such as cyclooctyne.
