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Prostheses with associated growth factors

A technology of growth factors and peptide growth factors, which is applied in the field of prostheses associated with growth factors, can solve problems such as unfavorable preservation techniques, increased chances of reoperation, and reduced durability

Inactive Publication Date: 2001-03-28
ST JUDE MEDICAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Preservation techniques that do not promote cell survival, such as long-term storage at 4°C, are associated with reduced persistence in vivo and increased chances of reoperation

Method used

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  • Prostheses with associated growth factors
  • Prostheses with associated growth factors
  • Prostheses with associated growth factors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Embodiment 1

[0082] EXAMPLES Example 1: Direct VEGF Association

[0083] This example demonstrates the ability of VEGF to associate with cross-linked tissue, and the relative effectiveness of VEGF in stimulating attachment of viable endothelial cells to tissue.

[0084] Prepare the following solutions. 5 liters of glutaraldehyde solution was prepared by adding 19.3 g NaCl, 70.0 g sodium citrate, 2.5 g citric acid, 50 ml 50% by volume glutaraldehyde (Electronic Spectroscopy Sciences, Fort Washington, PA), and sufficient amount of Phase osmosis pure water (RO warer) preparation. The VEGF solution was prepared by dissolving 50 μg / ml VEGF stock solution (human recombinant VEGF 165 , R&D Systems, Minneapolis, MN) diluted to a final concentration of 100 ng / ml. A HEPES buffered saline solution was prepared by adding 17.4 g NaCl and 35.7 g HEPES free acid to 3 liters of RO water. An 80% ethanol solution was prepared by hydrating 1.8 g NaCl, 3.8 g HEPES free acid, 1684 ml 95% ethanol (Worum Che...

Embodiment 2

[0109] Similar results were found in other experiments (glutaraldehyde crosslinked leaflets cultured in 100 ng / ml VEGF). Specifically, VEGF enhanced the growth of HUVEC and human aortic endothelial cells in the lobules within 5-30 days of culture. Additional experiments also showed that VEGF attachment to the leaflets was most efficient when the leaflets were stored in HEPES buffered glutaraldehyde solution for less than one month prior to incubation with VEGF. Example 2: Cross-linking of VEGF glutaraldehyde to ethanol-treated cross-linked tissue

[0110] This example demonstrates that a low concentration of glutaraldehyde solution can effectively cross-link VEGF to ethanol-treated glutaraldehyde-crosslinked tissue without reducing the ability of VEGF to stimulate endothelial cell proliferation and chemotaxis.

[0111] All solutions were prepared fresh on the day of use and filtered through a 0.25 μm filter. HEPES buffered saline solution consisted of 0.1 M NaCl and 50 mM HE...

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Abstract

A polypeptide growth factor is associated with a substrate to promote population of the substrate with endothelial cells. A prosthesis is formed with growth factor crosslinked to the substrate. Preferred polypeptide growth factors include VEGF. VEGF treated tissue can be populated with endothelial cells in vitro and / or in vivo. In an alternative approach, VEGF can be associated with the substrate by direct contact with a VEGF solution, application of the VEGF with an adhesive as a coating to the substrate, or chemical binding of the VEGF to the substrate with or without an intervening linker molecule. In one preferred approach, the growth factor is associated with the substrate by crosslinking under suitably mild conditions such that the growth factor is active following the crosslinking process.

Description

technical field [0001] The present invention relates to prostheses having components modified by polypeptide growth factors. The invention further relates to methods of making these prostheses. Background technique [0002] Prostheses, ie prosthetic devices, are used to repair or replace damaged or diseased organs, tissues or other structures in humans and animals. Because prostheses are usually implanted in the body for long periods of time, they are usually biocompatible. For example, prostheses may include artificial hearts, artificial heart valves, ligament repair materials, vascular prostheses, surgical patches composed of mammalian tissue, and the like. [0003] Prostheses can be constructed from natural materials such as tissue, synthetic materials or combinations thereof. For example, synthetic prostheses, such as mechanical heart valve prostheses, are prepared from biocompatible metals and other materials such as graphite and polyester. Although mechanical heart...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61F2/02A61F2/04A61F2/10A61F2/24A61K38/22A61L27/00A61L27/22A61L27/36A61L31/00A61L31/04
CPCA61L27/3808A61L31/005A61L31/047A61L27/3645A61L27/227A61L27/3843A61L27/3625A61L27/3604A61L27/3687
Inventor 文达·C·卡莱尔希拉·J·凯利马修·F·奥格莱
Owner ST JUDE MEDICAL