Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ (in its original position or place) tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system. Research has not yet reached the stage of clinical trials.
Procedure
Scaffolds Various biomaterials, whether they are biological, synthetic, or a combination of both, can be used to create scaffolds, which when implanted in a human body can promote host tissue regeneration. First, cells from the patient in which the scaffold will be implanted in are harvested. These cells are expanded and seeded into the created scaffold, which is then inserted inside the human body. The human body serves as a bioreactor, which allows the formation of an extracellular matrix (ECM) along with fibrous proteins around the scaffold to provide the necessary environment for the heart and circulatory system. The initial implantation of the foreign scaffold triggers various signaling pathways guided by the foreign body response for cell recruitment from neighboring tissues. The new nanofiber network surrounding the scaffold mimics the native ECM of the host body. Once cells begin to populate the cell, the scaffold is designed to gradually degrade, leaving behind a constructed heart valve made of the host body's own cells that is fully capable of cell repopulation and withstanding environmental changes within the body. The scaffold designed for tissue engineering is one of the most crucial components because it guides tissue construction, viability, and functionality long after implantation and degradation.
Biological
Biological scaffolds can be created from human donor tissue or from animals; however, animal tissue is often more popular since it is more widely accessible and more plentiful. Xenograft, from a donor of a different species from the recipient, heart valves can be from either pigs, cows, or sheep. If either human or animal tissue is used, the first step in creating useful scaffolds is decellularization, which means to remove the cellular contents all the while preserving the ECM matrix, which is advantageous compared to manufacturing synthetic scaffolds from scratch. Many decellularization methods have been used such as the use of nonionic and ionic detergents that disrupt cellular material interactions or the use of enzymes to cleave peptide bonds, RNA, and DNA.
Fabricated There are also current approaches that are manufacturing scaffolds and coupling them with biological cues. Fabricated scaffolds can also be manufactured using either biological, synthetic, or a combination of both materials from scratch to mimic the native heart valve observed using imaging techniques. Since the scaffold is created from raw materials, there is much more flexibility in controlling the scaffold's properties and can be more tailored. Some types of fabricated scaffolds include solid 3-D porous scaffolds that have a large pore network that permits the flow through of cellular debris, allowing further tissue and vascular growth. 3-D porous scaffolds can be manufactured through 3-D printing or various polymers, ranging from polyglycolic acid (PGA) and polylactic acid (PLA) to more natural polymers such as collagen. Fibrous scaffolds have the potential to closely match the structure of ECM through its use of fibers, which have a high growth factor. Techniques to produce fibrous scaffolds include electrospinning, in which a liquid solution of polymers is stretched from an applied high electric voltage to produce thin fibers. Conversely to the 3-D porous scaffolds, fibrous scaffolds have a very small pore size that prevents the pervasion of cells within the scaffold. Hydrogel scaffolds are created by cross-linking hydrophilic polymers through various reaction such as free radical polymerization or conjugate addition reaction. Hydrogels are beneficial because they have a high water content, which allows the ease of nutrients and small materials to pass through.
Biocompatibility The biocompatibility of surgically implanted foreign biomaterial refers to the interactions between the biomaterial and the host body tissue. Cell line as well as cell type such as fibroblasts can largely impact tissue responses towards implanted foreign devices by changing cell morphology. Thus the cell source as well as protein adsorption, which is dependent on biomaterial surface property, play a crucial role in tissue response and cell infiltration at the scaffold site.
Methodology
Inflammatory response
Acute inflammation Implantation of any foreign device or material through the means of surgery results in at least some degree of tissue trauma. Therefore, especially when removing a native heart valve either partially or completely, the tissue trauma will trigger a cascade of inflammatory responses and elicit acute inflammation. During the initial phase of acute inflammation, vasodilation occurs to increase blood flow to the wound site along with the release of growth factors, cytokines, and other immune cells. Furthermore, cells release reactive oxygen species and cytokines, which cause secondary damage to surrounding tissue. These chemical factors then proceed to promote the recruitment of other immune responsive cells such as monocytes or white blood cells, which help foster the formation of a blood clot and protein-rich matrix.
… excerpt ends here. Continue reading the full article.
