Phosphorylcholine (abbreviated ChoP) is the hydrophilic polar head group of some phospholipids, which is composed of a negatively charged phosphate bonded to a small, positively charged choline group. Phosphorylcholine is part of the platelet-activating factor; the phospholipid phosphatidylcholine and sphingomyelin, the only phospholipid of the membrane that is not built with a glycerol backbone. [1] Treatment of cell membranes, like those of RBCs, by certain enzymes, like some phospholipase A2, renders the phosphorylcholine moiety exposed to the external aqueous phase, and thus accessible for recognition by the immune system. [2] Antibodies against phosphorylcholine are naturally occurring autoantibodies that are created by CD5+/B-1 B cells and are referred to as non-pathogenic autoantibodies. [3]
In interventional cardiology, phosphorylcholine is used as a synthetic polymer-based coating, applied to drug-eluting stents, to prevent the occurrence of coronary artery restenosis. [4] The first application of this approach for use of stents evolved from efforts by Hayward, Chapman et al., who showed that the phosphorylcholine component of the outer surface of the erythrocyte bilayer was non-thrombogenicity. [5] Until 2002, over 120,000 phosphorylcholine-coated stents have been implanted in patients with no apparent deleterious effect in the long term compared to bare metal stent technologies. [6]
Drug-eluting stents (DES) are used by interventional cardiologists, operating on patients with coronary artery disease. The stent is inserted into the artery via a balloon angioplasty. This will dilate the diameter of the coronary artery and keep it fixed in this phase so that more blood flows through the artery without the risk of blood clots (atherosclerosis). [7]
Phosphorylcholine is used as the polymer-based coating of a DES because its molecular design improves surface biocompatibility and lowers the risk of causing inflammation or thrombosis. Polymer coatings of stents that deliver the anti-proliferative drug Zotarolimus to the arterial vessel wall are components of these medical devices. For targeted local delivery of Zotarolimus to the artery, the drug is incorporated into a methacrylate-based copolymer that includes a synthetic form of phosphorylcholine. This use of biomimicry, or the practice of using polymers that occur naturally in biology, provides a coating with minimal thrombus deposition and no adverse clinical effect on late healing of the arterial vessel wall. Not only is the coating non-thrombogenic, but it also exhibits other features that should be present when applying such a material to a medical device for long-term implantation. These include durability, neutrality to the chemistry of the incorporated drug and ability for sterilization using standard methods which do not affect drug structure or efficiency[ citation needed ]
Angioplasty, also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atherosclerosis.
In medicine, a stent is a tube usually constructed of a metallic alloy or a polymer. It is inserted into the lumen of an anatomic vessel or duct to keep the passageway open. Stenting refers to the placement of a stent. The word "stent" is also used as a verb to describe the placement of such a device, particularly when a disease such as atherosclerosis has pathologically narrowed a structure such as an artery.
A coronary catheterization is a minimally invasive procedure to access the coronary circulation and blood filled chambers of the heart using a catheter. It is performed for both diagnostic and interventional (treatment) purposes.
Restenosis is the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage, and subsequently become re-narrowed. This is usually restenosis of an artery, or other blood vessel, or possibly a vessel within an organ.
Coronary thrombosis is defined as the formation of a blood clot inside a blood vessel of the heart. This blood clot may then restrict blood flow within the heart, leading to heart tissue damage, or a myocardial infarction, also known as a heart attack.
Percutaneous coronary intervention (PCI) is a minimally invasive non-surgical procedure used to treat narrowing of the coronary arteries of the heart found in coronary artery disease. The procedure is used to place and deploy coronary stents, a permanent wire-meshed tube, to open narrowed coronary arteries. PCI is considered 'non-surgical' as it uses a small hole in a peripheral artery (leg/arm) to gain access to the arterial system, an equivalent surgical procedure would involve the opening of the chest wall to gain access to the heart area. The term 'coronary angioplasty with stent' is synonymous with PCI. The procedure visualises the blood vessels via fluoroscopic imaging and contrast dyes. PCI is performed by an interventional cardiologists in a catheterization laboratory setting.
A drug-eluting stent (DES) is a tube made of a mesh-like material used to treat narrowed arteries in medical procedures both mechanically and pharmacologically. DES is inserted into a narrowed artery using a balloon. Once the balloon inside the stent is inflated, the stent expands, pushing against the artery wall, keeping the artery open, thereby improving blood flow. The mesh design allows cells to grow through and around it, securing it in place.
A foreign body reaction (FBR) is a typical tissue response to a foreign body within biological tissue. It usually includes the formation of a foreign body granuloma. Tissue-encapsulation of an implant is an example, as is inflammation around a splinter. Foreign body granuloma formation consists of protein adsorption, macrophages, multinucleated foreign body giant cells, fibroblasts, and angiogenesis. It has also been proposed that the mechanical property of the interface between an implant and its surrounding tissues is critical for the host response.
The history of invasive and interventional cardiology is complex, with multiple groups working independently on similar technologies. Invasive and interventional cardiology is currently closely associated with cardiologists, though the development and most of its early research and procedures were performed by diagnostic and interventional radiologists.
A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in patients suffering from coronary heart disease. The vast majority of stents used in modern interventional cardiology are drug-eluting stents (DES). They are used in a medical procedure called percutaneous coronary intervention (PCI). Coronary stents are divided into two broad types: drug-eluting and bare metal stents. As of 2023, drug-eluting stents were used in more than 90% of all PCI procedures. Stents reduce angina and have been shown to improve survival and decrease adverse events after a patient has suffered a heart attack—medically termed an acute myocardial infarction.
Zotarolimus is an immunosuppressant. It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a carrier. Zotarolimus, or ABT-578, was originally used on Abbott's coronary stent platforms to reduce early inflammation and restenosis; however, Zotarolimus failed Abbott's primary endpoint to bring their stent/drug delivery system to market. The drug was sold/distributed to Medtronic for use on their stent platforms, which is the same drug they use today. Coronary stents reduce early complications and improve late clinical outcomes in patients needing interventional cardiology. The first human coronary stent implantation was first performed in 1986 by Puel et al. However, there are complications associated with stent use, development of thrombosis which impedes the efficiency of coronary stents, haemorrhagic and restenosis complications are problems associated with stents.
Nitinol biocompatibility is an important factor in biomedical applications. Nitinol (NiTi), which is formed by alloying nickel and titanium, is a shape-memory alloy with superelastic properties more similar to that of bone, when compared to stainless steel, another commonly used biomaterial. Biomedical applications that utilize nitinol include stents, heart valve tools, bone anchors, staples, septal defect devices and implants. It is a commonly used biomaterial especially in the development of stent technology.
A bare-metal stent is a stent made of thin, uncoated (bare) metal wire that has been formed into a mesh-like tube. The first stents licensed for use in cardiac arteries were bare metal – often 316L stainless steel. More recent "second generation" bare-metal stents have been made of cobalt chromium alloy. While plastic stents were first used to treat gastrointestinal conditions of the esophagus, gastroduodenum, biliary ducts, and colon, bare-metal stent advancements led to their use for these conditions starting in the 1990s.
Julio Palmaz is a doctor of vascular radiology at University of Texas Health Science Center at San Antonio. He studied at the National University of La Plata in Argentina, earning his medical degree in 1971. He then practiced vascular radiology at the San Martin University Hospital in La Plata before moving to the University of Texas Health and Science Center at San Antonio. He is known for inventing the balloon-expandable stent, for which he received a patent filed in 1985. It was recognized in Intellectual Property International Magazine as one of "Ten Patents that Changed the World" in the last century. His early stent research artifacts are now part of the medical collection of the Smithsonian Institution in Washington, DC. He continues to innovate on his initial designs, developing new endovascular devices.
A bioresorbable stent is a tube-like device (stent) that is used to open and widen clogged heart arteries and then dissolves or is absorbed by the body. It is made from a material that can release a drug to prevent scar tissue growth. It can also restore normal vessel function and avoid long-term complications of metal stents.
Biomaterials are materials that are used in contact with biological systems. Biocompatibility and applicability of surface modification with current uses of metallic, polymeric and ceramic biomaterials allow alteration of properties to enhance performance in a biological environment while retaining bulk properties of the desired device.
Biomaterials exhibit various degrees of compatibility with the harsh environment within a living organism. They need to be nonreactive chemically and physically with the body, as well as integrate when deposited into tissue. The extent of compatibility varies based on the application and material required. Often modifications to the surface of a biomaterial system are required to maximize performance. The surface can be modified in many ways, including plasma modification and applying coatings to the substrate. Surface modifications can be used to affect surface energy, adhesion, biocompatibility, chemical inertness, lubricity, sterility, asepsis, thrombogenicity, susceptibility to corrosion, degradation, and hydrophilicity.
Neointimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in the thickening of arterial walls and decreased arterial lumen space. Neointimal hyperplasia is the major cause of restenosis after percutaneous coronary interventions such as stenting or angioplasty. The term neointima is used because the cells in the hyperplastic regions of the vascular wall have histological characteristics of both intima and normal artery cells.
A dual therapy stent is a coronary artery stent that combines the technology of an antibody-coated stent and a drug-eluting stent. Currently, second-generation drug-eluting stents require long-term use of dual-antiplatelet therapy, which increases the risk of major bleeding occurrences in patients. Compared to drug-eluting stents, dual therapy stents have improved vessel regeneration and cell proliferation capabilities. As a result, dual therapy stents were developed to reduce the long-term need for dual-antiplatelet therapy.
Drug eluting implants encompass a wide range of bioactive implants that can be placed in or near a tissue to provide a controlled, sustained or on demand release of drug while overcoming barriers associated with traditional oral and intravenous drug administration, such as limited bioavailability, metabolism, and toxicity. These implants can be used to treat location-specific and surrounding illness and commonly use 3D printing technologies to achieve individualized implants for patients.