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.