Proteins are incorporated into protein or polysaccharide matrices for use
in tissue repair, regeneration and/or remodeling and/or drug delivery.
The proteins can be incorporated so that they are released by degradation
of the matrix, by enzymatic action and/or diffusion. As demonstrated by
the examples, one method is to bind heparin to the matrix by either
covalent or non-covalent methods, to form a heparin-matrix. The heparin
then non-covalently binds heparin-binding growth factors to the protein
matrix. Alternatively, a fusion protein can be constructed which contains
a crosslinking region such as a factor XIIIa substrate and the native
protein sequence. Incorporation of degradable linkages between the matrix
and the bioactive factors can be particularly useful when long-term drug
delivery is desired, for example in the case of nerve regeneration, where
it is desirable to vary the rate of drug release spatially as a function
of regeneration, e.g. rapidly near the living tissue interface and more
slowly farther into the injury zone. Additional benefits include the
lower total drug dose within the delivery system, and spatial regulation
of release which permits a greater percentage of the drug to be released
at the time of greatest cellular activity.