US5256418A — Collagen constructs

Claim 1

Independent Claim 107 words

A method of forming a construct comprising collagen, the method comprising the steps of: (a) providing an aqueous solution comprising collagen adjacent a permeable member, the permeable member being substantially impermeable to collagen and in contact with a concentrating agent, wherein the concentrating agent has an osmotic pressure higher than that of the collagen solution and permits selective mass transfer of solvent from the collagen solution through the permeable member; and (b) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the selective mass transfer of solvent from the collagen solution and the formation of the collagen construct at the permeable member.

Claim 2

Independent Claim 107 words

A method of forming a construct comprising collagen, the method comprising the steps of: (a) providing an aqueous solution comprising collagen adjacent a permeable member, the permeable member being substantially impermeable to collagen and in contact with a concentrating agent, wherein the concentrating agent has an osmotic pressure higher than that of the collagen solution and permits selective mass transfer of solvent from the collagen solution through the permeable member; and (b) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the selective mass transfer of solvent from the collagen solution and the formation of the collagen construct at the permeable member.

Claim 3

Dependent Claim 18 words

The method of claim 1, further comprising the step of causing fibrils to form in the collagen construct.

Claim 4

Independent Claim 15 words

The method of claims 1 or 2, wherein the concentrating agent comprises a water-soluble polymer.

Claim 5

Dependent Claim 18 words

The method of claim 3, wherein the concentrating agent comprising at least one of polyethylene glycol and dextran.

Claim 6

Dependent Claim 16 words

The method of claim 3, wherein the concentrating agent comprises a polymer in phosphate buffered saline.

Claim 7

Dependent Claim 20 words

The method of claim 5, wherein the concentrating agent comprises a solution of polyethylene glycol or dextran in sodium chloride.

Claim 8

Dependent Claim 28 words

The method of claim 6, wherein the concentrating agent comprises a solution of 20% weight/volume polyethylene glycol having a molecular weight of about 8000 in phosphate buffered saline.

Claim 9

Dependent Claim 36 words

The method of claim 2, wherein the concentrating agent comprises a polymer in phosphate buffered saline, and the fibrils are caused to form by means of increasing the pH and ionic strength of the concentrating agent.

Claim 10

Independent Claim 20 words

The method of claims 1 or 2, wherein the collagen concentration of the construct is about 50 to 100 mg/ml.

Claim 11

Independent Claim 20 words

The method of claims 1 or 2, wherein the collagen concentration of the construct is at least about 100 mg/ml.

Claim 12

Independent Claim 14 words

The method of claims 1 or 2, wherein the permeable member comprises a membrane.

Claim 13

Dependent Claim 22 words

The method of claim 11, wherein the membrane comprises a porous ceramic or stainless steel material, dialysis tubing, or a nucleopore membrane.

Claim 14

Independent Claim 15 words

The method of claims 1 or 2, wherein the permeable member is flat or tubular.

Claim 15

Independent Claim 18 words

The method of claims 1 or 2, further comprising the step of providing cells to the collagen construct.

Claim 16

Dependent Claim 17 words

The method of claim 14, wherein the cells are at least one of endothelial and epithelial cells.

Claim 17

Independent Claim 18 words

The method of claims 1 or 2, further comprising the step of forming pores in the collagen construct.

Claim 18

Dependent Claim 14 words

The method of claim 16, wherein pores are formed by lyophilyzing the collagen construct.

Claim 19

Dependent Claim 35 words

The method of claim 16, wherein the pores are formed by means of incorporating a polymer in the collagen construct and the method further comprises the step of removing the polymer from the collagen construct.

Claim 20

Dependent Claim 14 words

The method of claim 18, wherein the polymer is polyvinyl alcohol or hyaluronic acid.

Claim 21

Dependent Claim 17 words

The method of claim 2, further comprising the step of cross-linking the fibrils in the collagen construct.

Claim 22

Dependent Claim 18 words

The method of claim 20, wherein the fibrils are cross-linked by air-drying, lyophilizing or contact with an aldehyde.

Claim 23

Dependent Claim 20 words

The method of claim 20, wherein the collagen construct has a burst strength of about 300 to 1000 mm Hg.

Claim 24

Dependent Claim 19 words

The method of claim 20, wherein the collagen construct has a burst strength of greater than 1000 mm Hg.

Claim 25

Independent Claim 30 words

The method of claims 1 or 2, wherein the collagen solution is at a concentration of about 5 to 10 mg/ml collagen and a pH of about 2 to 4.

Claim 26

Independent Claim 17 words

The method of claims 1 or 2, wherein the collagen construct is provided with a support member.

Claim 27

Dependent Claim 12 words

The method of claim 25, wherein the support member comprises a polyester.

Claim 28

Independent Claim 30 words

The method of claims 1 or 2, wherein the collagen solution further comprises at least one of an angiogenic factor, an anti-inflammatory agent, a chemotactic agent, or a collagenase inhibitor.

Claim 29

Independent Claim 88 words

A method of forming a tubular collagen construct in accordance with claims 1 or 2 by use of a device having an inner and outer chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing the solution comprising collagen the outer chamber; (b) providing the concentrating agent to the inner chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the collagen construct to form at the permeable member.

Claim 30

Independent Claim 88 words

A method of forming a tubular collagen construct in accordance with claims 1 or 2 by use of device having an inner and outer chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing the solution comprising collagen to the inner chamber; (b) providing the concentrating agent to the outer chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the collagen construct to form at the permeable member.

Claim 31

Independent Claim 139 words

A method of forming a multi-layer tubular collagen chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing a first solution comprising collagen at a pH of about 2 to 4 to the outer chamber; (b) providing a concentrating agent to the inner chamber; (c) maintaining the first collagen solution, permeable member and concentrating agent under conditions sufficient to enable the tubular collagen construct to form at the permeable member; (d) replacing the first collagen solution with a second solution comprising collagen; and (e) maintaining the second collagen solution, permeable member and concentrating agent under conditions sufficient to enable a second tubular construct to form outwardly of the first tubular construct; and (f) repeating steps (d) and (e) if additional layers of tubular collagen construct are desired.

Claim 32

Independent Claim 139 words

A method of forming a multi-layer tubular collagen chamber, the interface between the inner and outer chamber comprising a tubular permeable member, the method comprising the steps of: (a) providing a first solution comprising collagen at a pH of about 2 to 4 to the outer chamber; (b) providing a concentrating agent to the inner chamber; (c) maintaining the first collagen solution, permeable member and concentrating agent under conditions sufficient to enable the tubular collagen construct to form at the permeable member; (d) replacing the first collagen solution with a second solution comprising collagen; and (e) maintaining the second collagen solution, permeable member and concentrating agent under conditions sufficient to enable a second tubular construct to form outwardly of the first tubular construct; and (f) repeating steps (d) and (e) if additional layers of tubular collagen construct are desired.

Claim 33

Independent Claim 22 words

The method of 30, further comprising the step of causing fibrils to form in at least one layer of the collagen construct.

Claim 34

Independent Claim 22 words

The method of 30, further comprising the step of causing fibrils to form in at least one layer of the collagen construct.

Claim 35

Independent Claim 82 words

A method of forming a flat collagen construct by use of a device having an inner and outer container, the interface between the inner and outer chamber comprising a flat permeable member, the method comprising the steps of: (a) providing a solution comprising collagen to the inner chamber; (b) providing a concentrating agent to the outer chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the flat construct to form at the permeable member.

Claim 36

Independent Claim 82 words

A method of forming a flat collagen construct by use of a device having an inner and outer container, the interface between the inner and outer chamber comprising a flat permeable member, the method comprising the steps of: (a) providing a solution comprising collagen to the inner chamber; (b) providing a concentrating agent to the outer chamber; and (c) maintaining the collagen solution, permeable member and concentrating agent under conditions sufficient to enable the flat construct to form at the permeable member.

Claim 37

Independent Claim 58 words

A method of concentrating a solution of collagen comprising: (a) contacting a collagen solution with a permeable member, the permeable member being in contact with an agent for concentrating the collagen; (b) maintaining the collagen solution and concentrating agent under conditions sufficient to enable the collagen solution to reach a concentration of, from about 50 to 100 mg/ml.

Claim 38

Independent Claim 58 words

A method of concentrating a solution of collagen comprising: (a) contacting a collagen solution with a permeable member, the permeable member being in contact with an agent for concentrating the collagen; (b) maintaining the collagen solution and concentrating agent under conditions sufficient to enable the collagen solution to reach a concentration of, from about 50 to 100 mg/ml.

Claim 39

Dependent Claim 16 words

The method of claim 33, wherein the collagen solution reaches a concentration of about 100 mg/ml.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1996-10-25	1997-04-26	1997-10-26	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2000-10-25	2001-04-26	2001-10-26	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2004-10-25	2005-04-26	2005-10-26	$7700.00	Window Closed / Lapsed

Collagen constructs

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