With trending minimally invasive preference in treating a myriad of diseases, intraluminal stent technologies are rightfully gaining attention. Some of the world’s biggest medical device companies (Boston Scientific, Medtronics, Abbot, Cook, etc) also hold the largest portfolios of stents. When stents have been applied to human disease from head to toe, most conversations revolve around vascular stents, since it is the most common application. However, stents have been produced for other body parts, including the airways, the gut, the biliary system, and technically any anatomy that has a tubular structure. However, given the ability of 3D printing (a.k.a. additive manufacturing technologies) to provide personalizable medical devices with much more complex designs, 3D printed stents have been the latest focus of many device researchers and entrepreneurs around the world. The additional driving force behind commercializing 3D printed stents also includes the current unit economics of 3D printing technology. The intrinsic limitation of build size, advancements in microfabrication techniques, and a growing portfolio of bioresorbable and biocompatible materials. Of course, the same set of “potential” advantages is also where technological advancements are needed to reach the final destination. In this article, we intend to break down the medical stent industry, summarizing the current status and future development of this exciting device.
A. A brief history of stents
In a parallel universe to the world of 3D printing, the first clinical use of stents in medicine also happened in the 1980s, when Jacques Puel and Ulrich Sigwart first implanted a coronary stent into a patient in Toulouse, France. An occluded or stenotic coronary artery is the common cause of heart attacks and associated mortality. The stent was used as a scaffold to prevent the vessel from closing, either from atherosclerotic plague build-up over the years or from restenosis after traditional coronary artery surgery secondary to abnormal scarring. Shortly thereafter, in 1987, Julio Palmaz, who also invented a balloon-expandable stent, and Richard Schatz implanted a similar coronary stent into a patient in Germany. The first FDA-approved stent in the USA was created by Richard Schatz and coworkers. Named the Palmaz-Schatz (Johnson & Johnson) in late 1980s.
Since then, stent technology has revolutionalized medicine and ignited a trend toward minimally invasive treatments concurrent with many other emerging technologies to decrease mortality and morbidity, hospital stay, and associated costs with treating increasingly prevalent cardiovascular diseases. Medical specialties that have experienced simultaneous exponential professional growth over the last three decades after the invention of stents include interventional cardiologists, interventional radiologists, and cardiothoracic surgeons. In fact, nowadays, almost most cardiothoracic surgical trainees are trained in performing these nonsurgical minimally invasive transcatheter vascular procedures.
Since its initial invention, continuous innovation took place with stent technologies to include more functionalities and characteristics. Various stent coating was used to modify blood-biomaterial interactions after the adaption of bare-metal stents.
Next, the drug-eluting stent (DES) was introduced in 2003. A typical drug-eluting stent has a surface coating of high molecular polymer that contains drugs that prevent smooth muscle proliferation, a common reason for post-stenting restenosis. While contemporary DES has better outcomes than original bare-metal stents, there are still significant risks of failure or complication (like thrombosis) due to persistent local inflammation, loss of normal vessel geometry, and subsequent change in fluid dynamics.
The first commercialized bioresorbable stent was launched in 2012 by Abbot. The idea is a stent that not only can provide structural support to reperfuse a stenotic vessel, but also can be absorbed by the body over time. Both polymer and metal have been used for this type of stent. However, in 2017, FDA issued an official warning for their use due to apparently significantly increased risk for major cardiac events and complications compared to other options (e.g. DES).
Clearly, while new stents provide new promises, many innovations in stent design, material science, and manufacturing techniques are still needed to achieve the clinical outcomes humanity (and the market) has hoped for.
B. Current Status of Stent design
The basic concept of stent design
The basic concept of stenting involves placing a mesh inside the diseased blood vessel to keep it open and allow blood flow. This can be done via two different approaches: permanent and temporary. Permanent stents remain permanently in place, while temporary ones are stents that can be removed after the acute phase of the illness has passed (e.g. ureteral stent) or be absorbed by the body over time (for example Abbott’s Absorb coronary artery stents).
Stent design is a very active area of research. One of the most significant drawbacks of stents is restenosis, which requires more frequent follow-up angioplasties than conventional therapies. Moreover, some patients may not tolerate the presence of foreign materials within their bodies indefinitely. Therefore, new stent designs aim at improving these outcomes.
Factors to consider in stent design:
1. Material properties – What material should be used? Are there any limitations on its use? Is it toxic or non-biodegradable?
2. Mechanical properties – How does the stent expand? Does it need to withstand high pressures? Should it be flexible enough to navigate through tortuous vessels? One innovation in this space is a self-expanding (as opposed to balloon expending) stent. The stent is usually made of shape memory alloy wires that contract upon heating. This allows transcatheter deployment of stents more precisely and safer with a smaller system.
3. Biocompatibility – Will the stent interfere with the healing process? Can it be safely degraded?
4. Cost – How much will it cost to manufacture the stent?
5. Patient safety – Is the stent safe for long-term implantation?
6. Clinical outcomes – How effective is the stent compared to alternative treatment options?
What makes a good stent design?
Good stent design includes [Ref, Andronescu, et al]:
- “Ability to be crimped on the balloon catheter;
- Good expandability ratio;
- Sufficient radial hoop strength and negligible recoil;
- Sufficient flexibility;
- Adequate radiopacity/magnetic resonance imaging (MRI) compatibility;
- High thromboresistivity
- Absence of restenosis after implantation;
- Drug delivery capacity;
- Optimal biological properties to avoid crustation, biofilm formation, inflammation, and failure.”
C. Types of stents
There are many different kinds of stents as well as ways to categorize them since their invention. For now, there are two ways to categorize stents 1) Based on anatomy and 2) Based on materials. Other major categories of stents include drug-eluting stents (DES), biodegradable stents, and self-expanding stents as we have described above.
1. Types of stents based on anatomy
- Airway stents – This includes not just tracheal stents but also stents for the nasal passage, for example in cleft palate patients post repair.
- Cardiovascular stents – Since the human body is a host of vascular and lymphatic systems, these include not only arterial, and venous stents, but also some heart valves that can be delivered using transcatheter approaches. The mechanical property requirements for different types of vessels can be very different. For example, while stents used for coronary artery typically maintain their final shape after deployment, stents used for vessels in the limbs in the case of the peripheral vascular disease need to be able to have “shape memory” due to constant movements in these vessels. This plays a determining role in the design and material used for the stent.
- Esophageal stents and other gastrointestinal stents – Typically, these are used where there is obstructive tumor or stricture secondary to scarring.
- Biliary stent – It is for treating blocked bile duct secondary to stones or cancer.
2. Types of stents based on materials
- Drug eluted stent
- Nitinol stent
- Cobalt chromium stent
- Titanium alloy stent
- Stainless steel stent
- Covered stent
- Polymer stent
D. How are stents traditionally made
Laser cutting has been the traditional stent manufacturing technique. However, one significant concern with laser cutting of both polymer and metal is the heat-affected zone left by the laser. For metal stents, this issue is often taken care of by additional surface finishing like acid pickling or electropolishing to remove this layer and create an oxidized layer that is more corrosion resistant as well as more biocompatible. However, the thermal damage from laser cutting is harder to control with polymeric stents. In fact, additive manufacturing or electrospinning are preferred choices to manufacture polymeric stents. [Ref]
Additionally, the cost of laser cutting to create personalized stents with less standard shape and size is prohibitive.
Here is a video showing how laser cutting stent works:
E. Why do we need a 3D printed stent?
The upward trend of interest in developing 3D printed stents is evident by a simple search in Pubmed. One major driving force is the ability of 3D printing to create personalized medical devices. While some traditionally manufactured stents can be one-size-fit-all, or fit for the majority of the population, some disease treatments require a customized solution. The cost of a traditional stent manufacturing setup is prohibitive in creating more personalized and unique stents of a variety of sizes, geometries, and even materials.
Aside from size, the ability to create complex geometry such as a bifurcated stent is unsatisfying using the traditional laser cutting technique. Instead of having to match up two different stents to create a bifurcated stent, 3D printing can create one bifurcated device in one print.
Another increasing attractive reason to use additive manufacturing is the potential to create point-of-care delivery of medical devices. Hospitals or hospital-based manufacturing hubs could create personalized devices for their patients without the concerns of expensive inventory, supply chain challenges, and potentially cutting overhead costs.
Figure 1. The number of publications under the keyword “3D printed stents” over time.
F. What has been done so far to 3D print stents?
1. Which stents are already 3D printed?
Deformity of the airway can be due to a variety of reasons, including trauma, radiation, congenital malacia, the mass effect from the adjacent mediastinal tumor, or even lung transplant or repeated past failed stents. The sequala could be deadly hypoxia and/or pneumonia, due to obstruction of airflow and accumulation of mucus. Tracheobronchial stents have been available since the 1980s, with a typical configuration of two hollow tubes connected into a Y shape to fit the carina. Similar to vascular stents, a variety of metal, a nonmetal (esp. silicone), and hybrid materials have been used. In addition to high cost, difficulty in stent placement, migration, obstruction secondary to granulation tissue, erosion, and stent fracture (esp. metal stent), the traditional tracheobronchial stent is very limited and often the last option, hence the need for innovation.
Tracheal stents could potentially be the first commercialized human stents given recent clinical progress. Led by large academic institutions like the Cleveland Clinic and Mayo Clinic, 3D printed stents created were used to treat a variety of diseases, ranging from pediatric tracheobronchomalacia to complex tracheal stenosis, under FDA “compassionate use” (Expanded Access) approval. Many of the treated patients had failed conventional off-the-shelf stents or otherwise had no alternative treatment option. Typically, these are silicone-based stents created based on 3D printed molds according to the patient’s CT imaging data.
In 2021, as part of QuirofAM, the CIM center, the GEMAT research group, and Tractivus in Barcelona, have co-developed a 3D printer that can directly 3D print medical grade silicone to manufacture medical devices, without altering medical silicone used. The group suggests that their new silicone 3D printer can be modified to be used in cleanrooms and their process meeting quality standards like ISO 13485. While it is still to see the fully published research on this, the group claims that the tracheal silicone stent created using this technology could be superior in functionality than other conventionally manufactured silicone stents in terms of reduction in stent migration.
“Esophageal cancer is the seventh most common cancer in the world, and the sixth highest cause of cancer deaths worldwide. Unless diagnosed early, prognosis remains poor with a five-year survival rate of around 20 percent.” [Ref] In 2021, University of South Australia researchers developed the first drug eluted 3D printed esophageal stent for the treatment of esophageal cancer. This stent is customized to fit the patient’s specific geometries and maintains the patency of a diseased esophagus. The polyurethane 3D-printed stent is also loaded with 5-fluorouracil (5-FU), a common chemotherapy drug, with the ability to have a sustained drug release profile of over 110 days in vitro. While esophageal stent for treating esophageal cancer in itself is a common practice, the issue of tumor overgrowth in a traditionally stented esophagus remains to be a challenge. This type of drug eluted customized stent could allow more effective local chemotherapy delivery in addition to expanding stenotic diseased esophagus.
Endovascular Aortic Aneurysm Repair (EVAR) :
While not 3D printing the stent itself, being able to modify existing stents to fit individual patients’ unique anatomies potentially allow to enlarge the number of candidates eligible for EVAR. Studies have shown a small number of successful cases using 3D printed masks to fenestrate the stent-grafts in FEVAR (Fenestrated Endovascular Repair). [Ref]
Arterial Vascular Nitinol (Self-expandable) stent
In 2022, researchers at Australia’s national science agency, CSIRO, created the first 3D printed self-expanding nitinol stents made via powder bed fusion. (Note: Nitinol is an alloy of nickel and titanium.)
CSIRO’s nitinol stent demonstrates comparable flexibility and corrosion resistance in simulated body fluids as commercial stents of similar dimensions.
2. What materials have been used to create 3D printed stents?
A variety of polymer and metallic materials have been investigated for the suitability of stents. Major materials used so far include PCL, poly(ε-caprolactone), based materials, silicone, nitinol, and polyurethane. (See Table 1)
3. Which 3D printing processes have been used to 3D print stents?
While all 3D printing processes can be potentially used to 3D print stents, extrusion-based and powder bed fusion 3D printing processes seem to dominate the space at the moment. (See Table 1)
4. What are some of the challenges facing 3D printed stents?
A. Lack of 3D printable materials.
For example, the CSIRO nitinol stent project faced challenges in sourcing 3D printable nitinol powder for the powder bed fusion process to make the stents. Eventually, CSIRO was able to purchase custom-made nitinol powder according to ASTM standards for biomedical materials. It is very likely that more custom-made 3D printable materials will be needed for future 3D printed stents or medical devices in general.
B. Limited mechanical properties and durability testing
With few exceptions, most 3D printed stents are still in the research and development stage. Overall, there is a lack of data to ensure 3D printed stents are at least as equal as existing stents.
C. Sterility/Quality Control/Regulation
As with other new 3D printed medical devices, there is in general a lack of standardized quality control in massively producing these stents while meeting rigorous manufacturing and FDA standards (or other regulatory bodies). Sterility in complex 3D printed medical devices with various materials that can only survive in specific sterilization environments will also pose a challenge for implantable devices.
G. Who is commercializing 3D printing stents?
There are a handful of research institutions working on commercializing 3D printed stents and related technologies. These include but are not limited to:
CSIRO (The Commonwealth Scientific and Industrial Research Organisation)
Unfortunately, true commercial success is yet to be realized. Currently, only VisionAir 3D Stent Architect, a spin-out startup from Cleveland Clinic is a known startup focusing on 3D printed tracheal stents.
- 3D printing advances in the development of stents https://pubmed.ncbi.nlm.nih.gov/34624441/
- 3D printing: An appealing route for customized drug delivery systems https://www.sciencedirect.com/science/article/abs/pii/S037851732030716X?via%3Dihub
- A review on additive manufacturing in bioresorbable stent manufacture https://aip.scitation.org/doi/abs/10.1063/5.0051941
- Recent Advances in Manufacturing Innovative Stents https://pubmed.ncbi.nlm.nih.gov/32294908/
- Three-dimensional printed 5-fluorouracil eluting polyurethane stents for the treatment of
oesophageal cancers https://pubs.rsc.org/en/content/articlelanding/2020/bm/d0bm01355b
- Trends in use of 3D printing in vascular surgery: a survey https://pubmed.ncbi.nlm.nih.gov/31560185/
- 3D Printing and Personalized Airway Stents https://link.springer.com/article/10.1007/s41030-016-0026-y
Dr. Jenny Chen is trained as a neuroradiologist, and founder/CEO of 3DHEALS. Her main interests include next-generation education, 3D printing in the healthcare sector, automated biology, and artificial intelligence. She is an angel investor who invests in Pitch3D companies.
Rance Tino attained a Bachelor of Engineering (Biomedical Engineering)(Honours) at the Royal Melbourne Institute of Technology (RMIT) in 2017. Since graduation, Rance has continued the academic pathway at RMIT and have recently completed his PhD with the Victoria Comprehensive Cancer Centre (VCCC), Peter MacCallum Physical Sciences department in developing customisable Radiotherapy Phantoms using 3D printing (Additive Manufacturing) for end-to-end testing of personalised lung treatment plans.
References for Table I:
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2. Lim, C., et al., Rapid prototyping and tooling of custom-made tracheobronchial stents. The International Journal of Advanced Manufacturing Technology, 2002. 20(1): p. 44-49.
3. Meyer, W., et al., Soft polymers for building up small and smallest blood supplying systems by stereolithography. Journal of functional biomaterials, 2012. 3(2): p. 257-268.
4. Zarek, M., et al., 4D printing of shape memory‐based personalized endoluminal medical devices. Macromolecular rapid communications, 2017. 38(2): p. 1600628.
5. Kuang, X., et al., 3D printing of highly stretchable, shape-memory, and self-healing elastomer toward novel 4D printing. ACS applied materials & interfaces, 2018. 10(8): p. 7381-7388.
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8. Wu, Z., et al., Radial compressive property and the proof-of-concept study for realizing self-expansion of 3D printing polylactic acid vascular stents with negative Poisson’s ratio structure. Materials, 2018. 11(8): p. 1357.
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