Prostheses, i.e., prosthetic devices, are used to repair or replace damaged or diseased organs, tissues and other structures in humans and animals. Prostheses must be generally biocompatible since they are typically implanted for extended periods of time. For example, prostheses can include artificial hearts, artificial heart valves, ligament repair material, vessel repair, surgical patches constructed of mammalian tissue and the like.
Prostheses can be constructed from natural materials such as tissue, synthetic materials or a combination thereof. For example, synthetic prostheses such as mechanical heart valve prostheses are manufactured from biocompatible metals and other materials such as graphite and polyester. Although mechanical heart valves have the advantage of proven durability through decades of use, they are associated with a high incidence of blood clotting on or around the prosthetic valve. Blood clotting can lead to acute or subacute closure of the valve or associated blood vessel. For this reason, patients with implanted mechanical heart valves remain on anticoagulants for as long as the valve remains implanted. Anticoagulants impart a 3-5% annual risk of significant bleeding and cannot be taken safely by certain individuals.
Besides mechanical heart valves, heart valve prostheses can be constructed with tissue leaflets or polymer leaflets. Thrombosis and subsequent calcification are concerns associated with polymer heart valves. Calcification of these valves can lead to failure.
Prosthetic tissue heart valves can be derived from, for example, porcine heart valves or manufactured from other biological material such as bovine pericardium. Biological materials in prosthetic heart valves generally have profile and surface characteristics that generally provide laminar, nonturbulent blood flow. Therefore, intravascular clotting is less likely to occur than with mechanical heart valves. Unfortunately, prosthetic tissue heart valves are limited by a tendency to fail beginning about seven years following implantation. Valve degeneration is particularly rapid in young patients and during pregnancy.
Calcification, i.e., the deposition of calcium salts, especially calcium phosphate (hydroxyapatite), appears to be a major cause of degeneration. Efforts to address the calcification problem have included treating glutaraldehyde-fixed valve prostheses with compounds to reduce calcium nucleation. Other approaches include use of alternative tissue fixation techniques since evidence suggests that glutaraldehyde fixation can contribute to calcification and mechanical degradation. In addition, since nonviable cells can be sites for calcium deposition, various processes have been developed to remove nonviable cells while leaving the extracellular matrix intact. Intact tissue with viable cells has natural protection against calcification.
Another major disadvantage of tissue based prostheses is the failure of such devices to be self-maintaining. Long term durability is affected by the ability of viable cells to populate the implanted tissue and to carry out maintenance functions. The importance of viable cells has been studied in the context of homograft transplants, i.e., transplants from one member of a species to another member of the same species. Proper homograft preservation can maximize the number of viable cells remaining in the tissue as determined by matrix protein synthesis. Preservation techniques that do not promote cell survival, such as long term storage at 4° C., are associated with reduced in vivo durability and increased reoperation rates.