| 摘要 |
Matrices formed of materials which bind to growth factors, directly or indirectly, are used for controlled delivery of the growth factors, especially for use in tissue repair and/or regeneration. The matrices may have heparin bound thereto ionically or covalently, or heparin-like binding sites incorporated in the matrix forming materials. The heparin or heparin- like binding sites can bind to the growth factors. The ratio of binding site s to peptides or growth factors can be used to vary the kinetics of the binding, thereby providing a means to increase or decrease the rate of association of the growth factors with the matrix and thus the rate of delivery. A ratio of at least 1:1 heparin to growth factor is preferably used. Increasing the ratio decreases the rate of release. The dissociation kinetics of low affinity heparin-binding proteins are relatively fast, but a high number of binding sites allows rebinding of the growth factor before it can diffuse out of the matrix. Release can occur by diffusion of the growth factor out of the matri x prior to rebinding, or it can occur if the growth factor encounters a cell surface receptor before rebinding to a heparin site. The most preferred matr ix is heparin or peptides containing heparin binding sites bound to fibrin, capable of attaching heparin, a heparin-like polysaccharide, or a heparin-li ke polymer, and a growth factor or peptide fragment thereof having a basic domain that binds heparin. The matrices can be implanted directly, alone or in combination with cells,or implanted and seeded with cells, at a site wher e tissue repair or regeneration is desired. A particularly preferred applicati on is in regeneration and repair of nerves. The matrices can be coated on medical devices and implants. The matrices most preferably encourage and promote cellular ingrowth.
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