Modified protein matrices

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 19/00 (2006.01) A61K 9/00 (2006.01) A61K 47/48 (2006.01) A61L 27/20 (2006.01) A61L 27/22 (2006.01) A61L 27/52 (2006.01) A61L 27/54 (2006.01) C07K 14/52 (2006.01) C07K 14/705 (2006.01) C07K 14/755 (2006.01) C07K 14/78 (2006.01) C07K 14/81 (2006.01) C07K 17/00 (2006.01) C07K 14/475 (2006.01)

Patent

CA 2371462

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 sites 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 matrix 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 matrix is heparin or peptides containing heparin binding sites bound to fibrin, capable of attaching heparin, a heparin-like polysaccharide, or a heparin-like 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 where tissue repair or regeneration is desired. A particularly preferred application 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.

L'invention concerne des matrices formées de matières, qui se lient, directement ou indirectement, à des facteurs de croissance et qui sont utilisées pour la distribution régulée de ces derniers, notamment dans la réparation et/ou la régénération tissulaire. De l'héparine peut être fixée aux matrices de manière ionique ou covalente, ou des sites de fixation de type héparine peuvent être introduits dans les matières formant les matrices. Les matrices peuvent être implantées directement, seules en associées à des cellules, ou implantées et ensemencées au moyen de cellules, dans un site où la réparation ou la régénération tissulaire est souhaitée. Une application particulièrement préférée est la régénération et la réparation nerveuses. Les matrices peuvent recouvrir des dispositifs et des implants médicaux. Elles favorisent de préférence l'interposition cellulaire.

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