# US 7,608,454 B2 · Vascularization enhanced graft constructs

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- Number: US 7,608,454 B2
- Document ID: US7608454B2
- Status: Granted
- Kind: B2
- Application number: 10/428,355
- Filed: 2003-05-02
- Published: 2003-11-20
- Granted: 2009-10-27
- Earliest claimed: 2002-05-02
- Assignees: Purdue Research Foundation
- Inventors: Stephen F. Badylak
- Web page: https://patentgrep.com/patent/US7608454B2

## Abstract

A tissue graft construct for use in repairing diseased or damaged tissues is provided. The tissue graft construct comprises a matrix composition selected from the group consisting of liver basement membrane and extracts and hydrolysates thereof, and processed collagen from vertebrate non-submucosal sources, added endothelial cells, and at least one additional preselected, exogenous population of cells which enhance the initiation of vessel-like structures in the grant. The preselected population of cells can be a population of non-keratinized or keratinized epithelial cells or a population of mesodermally derived cells selected from the group consisting of fibroblasts, smooth muscle cells, skeletal muscle cells, cardiac muscle cells, multi-potential progenitor cells, pericytes, osteogenic cells, and any other suitable cell type, preferably selected based on the tissue to be repaired. Methods for enhancing the vascularization in vivo of these tissue graft constructs and for preparing these graft constructs are also provided.

## Claims

### Claim 1

A remodelable tissue graft construct having vessel-like structures for implantation into a host for use in repairing diseased or damaged tissues, said tissue graft construct comprising
(i) a matrix composition selected from the group consisting of liver basement membrane, extracts of liver basement membrane, and hydrolysates of liver basement membrane,
(ii) added endothelial cells,
(iii) at least one additional preselected, exogenous population of cells, and
(iv) vessel-like structures, wherein said additional population of cells enhances the initiation of formation of said vessel-like structures in said graft construct.

### Claim 2 (depends on 1)

The graft construct of claim 1 wherein the at least one additional cell population comprises a population of cells selected from the group consisting of keratinized epithelial cells, non-keratinized epithelial cells, and mesodermally derived cells.

### Claim 3 (depends on 1)

The graft construct of claim 1 wherein the at least one additional cell population comprises a population of smooth muscle cells.

### Claim 4 (depends on 1)

The graft construct of claim 1 wherein the at least one additional cell population comprises a population of smooth muscle cell progenitor cells.

### Claim 5 (depends on 1)

The graft construct of claim 1 wherein the at least one additional cell population comprises fibroblasts.

### Claim 6 (depends on 1)

The graft construct of claim 1 further comprising a heparinase.

### Claim 7 (depends on 1)

The graft construct of claim 1 further comprising a growth factor selected from the group consisting of vascular endothelial cell-derived growth factor, platelet-derived growth factor, a platelet-derived growth factor-like molecule, transforming growth factor β, and a serum growth factor.

### Claim 8 (depends on 1)

The graft construct of claim 1 wherein the matrix composition is seeded with the additional preselected population of cells after the matrix composition is seeded with the endothelial cells.

### Claim 9 (depends on 1)

The graft construct of claim 1 wherein the matrix composition is seeded with the endothelial cells after the matrix composition is seeded with the additional preselected population of cells.

### Claim 10 (depends on 1)

The graft construct of claim 1 wherein the matrix composition is seeded with the endothelial cells and the additional preselected population of cells simultaneously or nearly simultaneously.

### Claim 11

A remodelable vascularized tissue graft construct for implantation into a host for use in repairing diseased or damaged tissues, said tissue graft construct comprising
(i) a matrix composition selected from the group consisting of liver basement membrane, extracts of liver basement membrane, and hydrolysates of liver basement membrane,
(ii) added endothelial cells,
(iii) at least one additional preselected, exogenous population of cells, and
(iv) vessel-like structures, wherein said additional population of cells enhances the initiation of vascularization of said graft construct.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The graft construct of any of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11, wherein said matrix composition comprises liver basement membrane.