The stent manufacturing process differs for stents based on several factors. To ensure the appropriate manufacturing method is chosen, the final application of the stent is taken into consideration. Other factors determining the stent manufacturing process include stent material, form, fabrication, geometry, and additions.
For a material to be utilized in the manufacturing of a stent, it must exhibit exceptional corrosion resistance, have excellent biocompatibility, create minimal artifacts during MRI and be radiopaque. Two groups of materials are utilized to manufacture stents, metals, and polymers. Metals would include Nitinol, stainless steel, MP35N, Cobalt-Chromium, and other metallic alloys, while polymers would include nylon, polyurethane, and other polymer types. Before specific metals or polymers are chosen, it is first determined whether the stent should be balloon-expandable or self-expanding. Materials used for both balloon-expandable and self-expanding stents must have specific properties to have a fully functioning stent.
The ultimate material for balloon-expandable stents would have low yield stress and high elastic modulus. Low yield and high elastic modulus would ensure the stent can expand to the shape needed, make it deformable at manageable balloon pressures, and have minimal recoil when the balloon is deflated. Balloon-expandable stents are manufactured in small diameter sizes and expanded when inserted into the vessel. The most common material used for any stents is stainless steel. It is a highly corrosion-resistant material. Varieties of stainless steel can be easily deformable. The fully annealed form of stainless steel (316L) is a great candidate for balloon-expandable stents due to its deformability. Other materials with similar properties include tantalum, platinum alloys, niobium alloys, cobalt alloys, and polymers. Properties making them excellent materials for balloon-expandable stents are their radiopacity, higher strength, improved corrosion resistance, and better MR compatibility.
Self-expanding stents are manufactured in large diameters and are compressed during the delivery process, allowing them to expand back to their original size when inserted into the vessel. Therefore, the material used for self-expanding stents is chosen for its elastic properties. The materials should have low elastic modulus and high yield stress. The highest utilized material for self-expanding stents is Nitinol, a Nickel-Titanium alloy. Nitinol is known for its super-elasticity. The recovery of elastic deformations is up to 10% with Nitinol. Due to the limited elastic range of other materials, design options are limited. However, in its full-hard condition, stainless steel has enough elasticity for some self-expanding stent designs, along with special cobalt alloys.
Stent forms, also known as raw material forms, describe what form the stent material is at the start of the manufacturing process. They can be made from sheet, tubing, or wire, which may be round or flat. Most expanding stents are made from wire or tubing, with a few exceptions. After the pattern has been created for laser cut or chemically etched sheets, they must be rolled up to a tubular configuration. Some laser cut or chemically etched sheets have to be welded, or a unique mechanical locking feature holds the tubular configuration.
There are five commonly used stent fabrication processes: etching, micro-electro discharge machining, electroforming, die-casting, and laser cutting and welding. The method used mainly depends on the raw material form.
Photolithography is the process of transferring shapes from a template onto a surface using light; the etching method is based on this. A plain sheet is first prepared with a coat of photoresist, a light-sensitive material. The chosen mask pattern is then projected onto the sheet. The desired pattern can then be developed and etched after the exposure.
The micro-electro discharge machining process, also known as Micro-EDM, is a thermoelectric process used to remove metal by electric discharge. Electric discharge sparks are generated between the closely spaced electrodes. The electric discharge is used as the cutting tool to erode the unwanted material from the parent metal through the process of melting and vaporization, producing the final desired product.
Electroforming is the process of metal buildup on a mandrel through electrodeposition to create the final object. Before the electrodeposition may begin, the mandrel goes through the etching process. Etching allows the exposure of the appropriate pattern on the mandrel when going through the electrodeposition process. After the mandrel and metal are placed into the electrolytic solution containing salts of the metal being electroformed, a direct current is passed through, starting the electrodeposition process. The process is continued until the desired thickness is achieved. The final step is harvesting the metal deposit removing the product from the mandrel.
The die-casting process uses molten metal and molds to create the final product. A mold or cast is made of the desired item, which is then filled with melted metal. To ensure proper distribution of the metal in the mold and prevent porosity, the molds are rotated to fill the fine details the mold may have. Molds created for the die-casting process may be of the desired sent design or of tubes or sheets used in the other manufacturing methods, making this process one that can be used alone or alongside another mentioned here.
The most common and vastly used stent manufacturing method is laser cutting. Excess material is removed from the parent tube or rod using a high energy density laser, creating the desired stent design and shape. The type of laser used may depend on specifics when cutting stents. Standard lasers used in the stent manufacturing process are flashlamp-pumped Nd:YAG lasers, fiber lasers, disk lasers, excimer lasers, and ultrashort pulse lasers. Cutting techniques also vary based on the laser being used. Due to the different heat temperatures introduced to the stent, dry or wet cutting processes may be used based on the pulses and interaction time of the laser to the metal. The stent material also has a role in which type of laser is used. Long pulse lasers are not ideal when cutting polymer stents due to the low melting point of polymer material.
Stents manufactured by braiding or knitting thin metals wires go through the laser welding process. Laser welding is used to join the wires together to form the desired geometry of the stent. Depending on the stent, there may be a wide variety of individual welds needed to manufacture each stent, varying from 10 to 100 welds per stent.
Stent geometries are categorized into five categories: coil, helical spiral, woven, individual rings, and sequential rings. These five categories are the high-level categories, with the following sub-categories.
The coil design is the most common in non-vascular applications. The unique design allows for extreme flexibility, assisting in easy retrieval and removal of the stent after implantation. However, this vastly decreases the strength of the stent.
Helical spiral designs have minimal internal connections points, promoting the stent’s flexibility and lack of longitudinal support. The flexibility and minimal connection points increase the elongation and compression needed during the stent implantation.
Braided and knitted stents fall into the woven category of stent geometries. These are constructed from multiple strands of wires. While the braiding and knitting design present exceptional coverage, they tend to shorten significantly during the expansion of the stent. The strength of the braided structure highly depends on the axial fixation of its ends.
Individual rings are typically used in supporting grafts or other prostheses. They may be attached to the graft material during manufacturing or individually sutured onto it after manufacturing. These single “Z” shaped rings are typically not used alone as stents but rather as a support for other types of stents.
Sequential rings are stents compromised of struts, expandable Z-shaped structural elements, joined by connecting bridges, hinges, or nodes. The sequential rings category can further refine the structural elements, connections, and resulting cells’ nature. The two main sub-categories for sequential rings are closed and open cell. Closed-cell design is when all internal inflection points are connected by bridging elements. Open-cell design is the opposite, where some or all internal inflection points are not connected using bridges.
There is a range of modifications additions that can be made in the stent manufacturing process. These include covering, radiopaque markers, radiopaque coating, biocompatibility coatings, and drug-eluting coating.
Also known as grafts, coverings are made of impermeable fabric, either polytetrafluoroethylene or polyester. The covering creates a barrier between the diseased arterial wall and stent and provides a smooth flow conduit. A physical barrier to restenosis is also created with coverings. The type of covered stent used is determined by the stent application, as vessel diameters, lesion lengths, and anatomic location vary for each case. Coverings can cover the stent or sewn directly onto the stent frame.
Radiopaque markers and radiopaque coating are also known as radiopacity enhancements. The basic materials used to make stents typically have a low visibility fluoroscopically. To increase visibility, markers can be attached to stents. Depending on the base material of the stent, a specific type of marker may be used. Gold, platinum, or tantalum are typically used for the markers. These markers can be sleeves that are crimped around a strut, rivets coined into tabs at the end of the stent, or integrated into a strut or welded-on tabs. Electroplating is also used to enhance visibility in X-rays.
The primary purpose of biocompatibility coatings is to prevent the rejection of the stent and protect the host and stent, prolonging the stent’s lifespan. Stents need to withstand certain factors in the body, such as proteins, glucose, and the adhesion of cells. Materials for biocompatibility coatings include tantalum coating, carbon coating, silicon carbide, and phosphorylcholine.
Drug-eluting coatings are used to prevent future complications after stent implantation. First-generation drug-eluting stents used paclitaxel and sirolimus. Paclitaxel is an anti-cancer chemotherapy drug. It is used to prevent cell proliferation and neointimal hyperplasia. Sirolimus is an immunosuppressive drug used together with other medicines to prevent the rejection of the stent. After further research of the drug properties, it was determined that sirolimus was a natural antibiotic with powerful immunosuppressive and high anti-restenotic properties. The success of sirolimus led to the -limus family of drugs in the new generation of drug-eluting stents. These drugs include everolimus, zotarolimus, umirolimus, novolimus and amphilimus. Each differs in structure, potency, molecular weight, and lipophilicity. Even with the different types of drugs that can be used for drug-eluting stents, immunosuppressants and cancer-fighting drugs, the objective is to prevent restenosis and future complications.
The stent manufacturing process and components are constantly being innovated. The role of different stent materials, geometries, and other aspects continue to be studied to incessantly improve the performance and broaden the uses for medical stent components. The continuous improvements on stent additions and modifications are also studied to further advance stent performance and uses. A radiopaque marker technology developed by ProPlate®, Vizi-Band®, is an excellent example of further studies to improve radiopaque enhancements for stent and braid applications.