Implant material

Details Implant material Implant material

2001-05-15

2003-09-30

Isabella, David J. (Department: 3738)

Surgery

Blood vessel or graft preparation

C623S916000

Reexamination Certificate

active

06626823

ABSTRACT:

FIELD OF INVENTION
The present invention relates generally to tissue implant material for use in grafting procedures. More particularly, the present invention provides non-vascular tissue for use as vascular graft material. The present invention further contemplates a method of vascular grafting using non-vascular tissue. The tissue of the present invention is preferably autologous relative to the recipient of the graft and is conveniently prepared around or on a molding support inserted into a body cavity of the intended recipient of the graft. The tissues and methods of the present invention are particularly useful in the treatment or prophylaxis of diseased or damaged blood vessels such as in atherosclerosis.
Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
BACKGROUND
Tissue grafting represents a major advance in the medical treatment of diseased or damaged tissue. In some cases, tissue grafting represents the sole avenue of medical treatment. However, the success of tissue grafting depends on a range of factors including the availability of suitable donor tissue and the extent of immunological intolerance by the recipient.
An example of grafting is vascular grafting which is one approach in dealing with atherosclerosis. Atherosclerosis is the principal cause of heart disease, stroke and gangrene of the extremities. Atherosclerotic lesions are a result of an inflammatory response to a damaged artery wall and is associated with excessive lipid deposition (Schwartz et al, 1993). The development of atherosclerosis (atherogenesis) is complex and involves several cell types such as macrophages, T-cells and smooth muscle cells of the intima. Atherosclerosis is responsible for a high rate of mortality and an even higher rate of long term physical impairment of subjects affected by this disease.
A method of treating atherosclerosis is to insert bypass grafts around an artery blocked by plaques. The most common vascular graft material is saphenous vein or mammary artery from the patients. Such graft material is referred to as an autograft. Vein and artery autografts are flexible, viable, non-thrombogenic and compatible. However, while the mammary artery seldom develops atherosclerosis, it may not always be the proper size or length, and saphenous vein may have varicose degenerative alterations that can lead to aneurysm formation when transplanted to a high pressure arterial site. Furthermore, the non-thrombogenic surface of endothelial cells of saphenous veins is often damaged during graft preparation.
Similarly, the use of dialdehyde starch tanned bovine xenografts has been generally abandoned due to a high incidence of aneurysm formation and poor resistance to infection.
For these reasons and because autologous grafts not always available, attempts have been made to produce synthetic vascular prostheses. The first synthetic vascular prosthesis was made of Vinyon-N and was implanted into a patient in the late 1940's. The patient died 30 minutes after the operation. Replacements have been made with nylon, then later with TEFLON which is polytetrafluoroethylene manufactured by DUPONT and DACRON which is a long-chainpolyester made from ethyleneglycol and tesephthalic acid manufactured by DUPONT. Nylon was found to lose most of its tensile strength after a brief period of implantation leading to aneurysmal dilation and graft rupture. Although both DACRON and TEFLON fabric grafts perform reasonably satisfactorily in high flow, low resistance conditions such as in the aorta, iliac and proximal femoral arteries, neither of these two materials is satisfactory for small caliber arterial reconstructions. Such grafts are compounded by graft failures from stenosis at the anastomic sites and excessive intimal hyperplasia. These complications are associated with graft thrombogenicity, poor healing and lack of compliance.
In the early 1970's, non textile vascular grafts prepared from expanded polytetrafluoroethylene (ePTFE) were introduced. ePTFE is the most chemically inert of all polymeric materials and is not degraded or changed in the chemical environment of the body and is extremely easy to suture. However, poor healing characteristics and lack of compliance are major causes for its lack of performance.
Indeed, the major problem with all synthetic vascular prostheses is that they are foreign bodies, so that blood coagulation can occur on their luminal surfaces causing occlusion in prostheses. One innovation designed to improve the patency of the synthetic vascular graft is to coat the lumen of the vascular graft with endothelial cells. While flow through the graft is improved and thrombogenesis reduced, graft failure can still occur due to occlusion by overgrowth of endothelial cells. In an attempt to control the growth, gene therapy has been used. This refinement addresses the overgrowth, but retrovirally transduced cells on the graft are not able to withstand the shear stresses encountered by flow of blood and are sheared off. Also, the procedure for obtaining endothelial cells from the patient is invasive and the cells are hard to propagate in vitro.
Tissue-polymer prostheses are available which incorporate a combination of tissue and synthetic material in the form of an integral composite. In one form, silicone mandrels covered with DACRON mesh are implanted beneath the cutaneous trunci muscles of sheep where they become encapsulated with ovine collagen (Koch et al, 1997). The tubes are then excised and trimmed of excess fat and connective tissue is then fixed with glutaraldehyde. The silicone mandrel is then removed leaving the fibre-reinforced tube which, after sterilization, is stored in ethanol (Edwards and Roberts, 1992). Although this prosthetic device has been successfully used, it does suffer the disadvantage of lacking elastin, an important component to prevent aneurysmal and dilatory changes from stretching both the collagen and mesh components. Further-more, the prosthetic device uses glutaraldehyde and this has the propensity to induce non-specific calcification of the implanted device.
In summary, despite considerable experimental and clinical research, none of the biological and synthetic grafts produced thus far is an ideal substitute for a blood vessel such as an artery, arterio-venous shunt or an access fistula. Limited availability, graft deterioration and complications such as thrombosis, aneurysm formation and excessive subintimal hyperplasia at the anastomotic sites are major problems.
There is a need, therefore, to develop tissue for use in vascular grafting which exhibits the biocompatibility of a recipient's own tissue but which is created artificially obviating the need to sacrifice existing, i.e. indigenous, tissue from the recipient. In accordance with the present invention, the inventors have identified a means of producing living graft issue for use as vascular tissue but which is derived from non-vascular tissue.
SUMMARY OF THE INVENTION
The present invention is predicated in part on the surprising observation that granulation tissue produced in a cavity of a live body in response to foreign material is useful as grafting material. The granulation tissue comprises non-thrombogenic, mesothelial (endothelial-like) cells overlying several layers of myofibroblasts which, in a preferred embodiment, is highly contractile, strong and responds to agonists and antagonists in a manner similar to smooth muscle in blood vessels. After grafting, elastic fibres are produced by the myofibroblasts.
Accordingly, one aspect of the present invention provides isolated tissue suitable for use in a vascular graft said tissue comprising granulation tissue produced on a molding support, and wherein the tissue is removed from the molding support prior to use.
Although this aspect of th

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