# US 2014/0193473 A1 · Materials and methods for controlling vasculogenesis from endothelial colony forming cells

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- Number: US 2014/0193473 A1
- Document ID: US20140193473A1
- Status: Published application
- Kind: A1
- Application number: 14/123,483
- Filed: 2012-06-06
- Published: 2014-07-10
- Earliest claimed: 2011-06-02
- Assignees: Indiana University Research and Technology Corporation
- Inventors: Mervin C. Yoder; Paul Critser; Sherry Voytik-Harbin
- Web page: https://patentgrep.com/patent/US20140193473A1

## CPC

- A61K 35/51: Umbilical cord; Umbilical cord blood; Umbilical stem cells
- A61K 9/70: Web, sheet or filament bases {; Films; Fibres of the matrix type containing drug (hollow drug-filled fibres A61K9/0092)}
- A61L 27/24: Collagen
- A61L 27/3808: {Endothelial cells}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)

## Abstract

Materials and methods are disclosed for controlling vasculogenesis using building blocks of a collagen matrix and endothelial colony forming cells (ECFC). The building blocks may be isolated by fractionating an acid soluble Type I collagen. The building blocks comprising monomers and/or oligomers may be recombined in desired ratios to alter the matrix microenvironment and to influence ECFC behavior.

## Claims

### Claim 1

A vessel forming matrix comprising:
a population of endothelial colony forming cells in a polymerized matrix comprising at least one fraction of an acid soluble Type I collagen.

### Claim 2 (depends on 1)

The matrix according to claim 1, wherein said at least one fraction of the acid soluble Type I collagen is selected from the group consisting of monomers having an average molecular weight of about 282 kDa and oligomers having an average molecular weight of about 603 kDa.

### Claim 3 (depends on 1)

The matrix according to claim 1, wherein said at least one fraction of acid soluble Type I collagen includes a telopeptide reactive aldehyde.

### Claim 4 (depends on 1)

The matrix according to claim 1, further comprising a second fraction of the acid soluble Type I collagen that differs from the at least one fraction.

### Claim 5 (depends on 4)

The matrix according to claim 4, wherein the at least one fraction is an oligomer-rich fraction and the second fraction is a monomer-rich fraction.

### Claim 6 (depends on 5)

The matrix according to claim 5, wherein the matrix comprises more of the oligomer-rich fraction than the monomer-rich fraction.

### Claim 7 (depends on 1)

The matrix according to claim 1, wherein said at least one fraction of acid soluble Type I collagen is present in the matrix at a concentration of about 0.5 to about 3.0 mg/ml.

### Claim 8 (depends on 1)

The matrix according to claim 1, wherein said population of endothelial colony forming cells is present in the matrix at a concentration of about 5×105 to about 2×106 cells/ml.

### Claim 9

A method of promoting vessel formation comprising the steps of:
obtaining an engineered collagen matrix from an oligomer-rich fraction of a Type I acid soluble collagen; and
seeding the matrix with a plurality of endothelial colony forming cells to form one or more vessels within the matrix.

### Claim 10 (depends on 9)

The method according to claim 9, wherein the matrix is richer in Type I acid soluble collagen oligomers than in Type I acid soluble collagen monomers.

### Claim 11 (depends on 9)

The method according to claim 9, wherein the average molecular weight of the collagen in the matrix is about 603 kDa.

### Claim 12 (depends on 9)

The method according to claim 9, wherein the average molecular weight of the collagen in the matrix is greater than about 282 kDa.

### Claim 13 (depends on 9)

The method according to claim 9, wherein the matrix has a collagen concentration of about 0.5 to about 3.0 mg/ml.

### Claim 14 (depends on 9)

The method according to claim 9, wherein the obtaining step comprises isolating oligomers from the Type I acid soluble collagen.

### Claim 15 (depends on 9)

The method according to claim 9, wherein the matrix is stiffer than the Type I collagen.

### Claim 16 (depends on 9)

The method according to claim 9, wherein the matrix is in an unpolymerized state during the seeding step.

### Claim 17 (depends on 9)

The method according to claim 9, wherein the seeding step comprises seeding the matrix with about 5×105 to about 2×106 cells/ml.

### Claim 18 (depends on 9)

The method according to claim 9, further comprising the step of implanting the matrix into a diseased area of a patient.

### Claim 19 (depends on 18)

The method according to claim 18, wherein the diseased area of the patient comprises an ischemic limb.

### Claim 20 (depends on 9)

The method according to claim 9, wherein the obtaining step comprises independently controlling a stiffness of the matrix and a collagen concentration of the matrix.
