Means for improving biocompatibility of implants, particularly of vascular grafts

• US 5,037,377 A
• Filed: 08/21/1986
• Issued: 08/06/1991
• Est. Priority Date: 11/28/1984
• Status: Expired due to Term

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Alonso, Manuel T.
• Primary Examiner(s): Cannon, Alan
• Application Number:
  US06/898,686
• Time in Patent Office: 1,811 Days
• Field of Search: 623/1, 623/66, 128/DIG. 8, 600/36
• US Class Current: 600/36
• CPC Class Codes: A61F 2/06 Blood vessels
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/48 with macromolecular fillers
• CPC Class Codes: C08L 89/06 derived from leather or skin , e.g. gelatin
• CPC Class Codes: Y10S 128/08 Collagen

Abstract

Implants containing a reasonably biocompatible fabric, which is to be exposed to blood flow after implantation, are rendered biocompatible and substantially impervious to blood, by applying a collagen composition containing soluble collagen, and preferably also collagen fibers, to the fabric in such a manner that the collagen composition penetrates into the interstitial spaces of the fabric. The fabric retaining collagen composition is then incubated at elevated temperature for sufficient time to form collagen fibers from the soluble collagen. Thereafter, the implant is dried. The steps of applying collagen composition, incubating and drying are repeated approximately two to four times. The implants, particularly when they comprise tubular vascular grafts, are tested for porosity by placing a pressurized column of aqueous solution, such as saline, into their interior. When the implant is sufficiently impervious to liquid, it is treated with a suitable cross-linking agent, such as glutaraldehyde solution, to bond adjacent collagen fibers to one another. When the implants are tubular vascular grafts, the treatment with glutaraldehyde is conducted in a longitudinally extended position of the graft, and with a pressurized column of glutaraldehyde placed within the interior of the tubular grafts.

Claims

1. A process for making a prosthetic material adapted for implantation into the human body in contact with blood flow in the human vascular system, the process comprising the steps of:

applying a solution of collagen to a reasonably biocompatible fabric which has interstitial spaces;

incubating the fabric having the applied collagen solution at an elevated temperature to obtain collagen fibers as a coating and in the interstitial spaces of the fabric, and

treating the fabric having collagen fibers with a solution of an aldehyde cross-linking agent to bond the fibers to one another.

2. The process of claim 1 wherein the steps of applying collagen and incubating are repeated several times.

3. The process of claim 1 further comprising the step of substantially drying the collagen fiber containing fabric after the step of applying.

4. The process of claim 1 wherein, in the step of treating the aldehyde, the cross-linking agent is glutaraldehyde.

5. A process for making a vascular graft having a tubular fabric base which has interstitial spaces wherethrough liquid can flow from the interior of the tubular base to its exterior, the process comprising the steps of:

applying a collagen composition containing soluble collagen to the fabric base and forcing the collagen solution to enter into the interstitial spaces of the fabric;

incubating the fabric base having the applied collagen composition at an elevated temperature for sufficient time to form collagen fibers from the predominant majority of the collagen solution retained in the fabric, and

thereafter treating the fabric base having the collagen fibers with a solution of an aldehyde cross-linking agent to form chemical bonds between adjacent fibers of collagen.

6. The process of claim 5 wherein the steps of applying collagen and incubating are conducted approximately two to four times.

7. The process of claim 5 wherein each step of applying and forcing collagen composition and subsequent step of incubating is followed by a step of drying the collagenated fabric base.

8. The process of claim 6 wherein in the step of applying and forcing, the collagen composition is forced into the interstitial spaces of the fabric by a differential existing between the pressure of the collagen composition present in the interior of the tubular vascular graft and the pressure which exists on the outside of the tubular graft.

9. The process of claim 8 wherein the collagen composition is pressurized in the interior of the tubular graft above ambient pressure.

10. The process of claim 8 wherein the collagen composition is maintained at approximately ambient pressure within the interior of the tubular graft, and wherein the pressure prevailing on the exterior of the tubular graft is decreased below ambient pressure.

11. The process of claim 8 additionally comprising at least one step of testing the porosity of the vascular graft having the collagen in the interstitial spaces of the fabric base by placing a pressurized column of aqueous solution into the interior of the tubular graft.

12. The process of claim 6 wherein the collagen composition comprises a mixture of soluble collagen and collagen fibers.

13. The process of claim 12 wherein the collagen composition comprises approximately equal volumes of collagen fibers and soluble collagen.

14. The process of claim 6 wherein during the step of treating, the tubular vascular graft is maintained in a substantially longitudinally extended position.

15. The process of claim 14 wherein the solution of the cross-linking agent is forced by pressure from the interior of the tubular base into the interstitial spaces of the fabric.