Polymer Based Scaffolds in Tissue Engineered Heart Valves

Peter Fong, Toshiharu Shin’oka, Reynold I. Lopez-Soler, Christopher Breuer. "Polymer Based Scaffolds in Tissue Engineered Heart Valves", Progress in Pediatric Cardiology, 2006. 193-9.

Summary:
The purpose heart valve is to control the blood flow to and from the heart. When the valve experiences restricted opening or leakage, a heart valve replacement may be necessary. The U.S. saw roughly 87,000 heart valve replacement surgeries in 2000; however, these replacements have shown to fail within 10 years in 50% of patients. This article gives an overview of the development of polymer based scaffolds in heart valve replacements devices.

A scaffold serves as a matrix on which neotissue can develop on the heart valve. A biological matrix, made up of xenografts or allografts, are seeded with endogenous cells to induce growth of neotissue. This type of matrix has greater biocompatibility, reduced immune response to implantation, and preservation of the structure of the heart valve compared to a synthetic matrix; however, studies have shown that this method can pose problems including calcification and tissue breakdown at the implant. The use of a synthetic matrix allows for the mechanical properties of the neotissue to be customized based on the design of the scaffold, since the properties of the tissue are determined after the development of the extracellular matrix. The structure can be altered by weaving of fibers or controlling the pore size to enhance cell adhesion. The polymers used in the synthetic matrix are also easily obtained 'off the shelf'. Another benefit is that the synthetic matrix can also provide temporary function to the structural tissues while the noetissue is developing.

The design of the synthetic scaffold has been refined over the years. The original scaffold was made of polygloycolic acid and polylactic acid copolymer. These materials were selected based on biocompatibility, bioresorbability, and the ease at which cells can attach and grow on their surfaces. Under this design, the device was stiffer and more rigid than their natural counterpart. The device was made more pliant through the introduction nonporous polyhydroxyoctanoate to the leaflets and between layers of polyglycolic acid in the conduit. However, the polyhydroxyoctanoate degrades at slower rates than rest of the scaffold, which could induce an immune response. Researchers have also worked with poly-4-hydroxybutyrate, a flexible thermoplastic, which serves as a coating on the scaffold, but only allows for partial endothelial cell coverage on the leaflets and presents some leakage in the valve.

There are two types of cells that make up the heart valve; the endothelial cells cover the surface of the valve wall, and the interstitial tissue made up of myofibroblasts that "construct, repair, and remodel the highly specialized and functionally designed extracellular matrix". There has been a lot of research to determine the best cell type to use in the heart valve replacement, none of which have been proven to be the perfect solution. Autologous endothelial and myofibroblast cells can be readily cultured and avoids the risk of immuno rejection, but require a substantial amount of time to grow. Harvesting stem cells is another possibility for the device. A promising study conducted by Perry et al. involved the use of ovine bone marrow derived from mesenchymal cells to seed a polymer scaffold in vitro. The results showed that cells had developed around the leaflet of the heart valve after 3 weeks of conditioning.
The environment in which the cells on matrix device grow affects the extracellular matrix and structure of the tissue. As a result, researchers have developed two implantation approaches. The "black box approach" involves implantation of the device in vivo, which causes the body to signals tissue repair and remodeling. The "bioreactor" approach induces stimulation of cell adhesion and enhance the biomechanical properties of the tissue in vitro.

While some there has been some clinical success in heart valve implantation in patients, many complications have arisen in other patients. Synthetic scaffolds have not been clinically used, but the techniques utilized in their development have been applied to natural biological scaffolds to improve upon the current designs.

Significance:
Heart valve dysfunction can be caused by infection, coronary artery disease, heart attack, or heart damage is a very serious issue affects that millions of Americans. The article outlined the different studies that have been conducted on the topic of heart valve replacement, but the results have been inconclusive. Although the synthetic scaffolds composed of polymeric materials have not very effective, they exhibit properties that could benefit patients. The paper suggests that applying the principles behind the synthetic scaffolds to autograft heart valves have great potential for success. Understanding cell adhesion to certain surfaces and the effects of cellular environments on mechanical responses of the device will allow for the development of a design that can closely replicate a natural heart valve.