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.[1][2]
In medicine, a
stent is any device which is inserted into a
blood vessel or other anatomical internal duct to expand it to prevent or alleviate a blockage. Traditionally, such devices are fabricated from metal mesh and remain in the body permanently or until removed through further surgical intervention. A bioresorbable stent (also called bioresorbable scaffold, biodegradable stent or naturally-dissolving stent) serves the same purpose, but is manufactured from a material that may dissolve or be absorbed in the body.[3]
Background
The use of metal
drug-eluting stents presents some potential drawbacks. These include a predisposition to late stent
thrombosis, prevention of late vessel adaptive or expansive remodeling, hindrance of surgical revascularization, and impairment of imaging with multislice
CT.[4][5]
To overcome some of these potential drawbacks, several companies are pursuing the development of bioresorbable scaffolds or bioabsorbable stents. Like metal stents, placement of a bioresorbable stent will restore blood flow and support the vessel through the healing process. However, in the case of a bioresorbable stent, the stent will gradually resorb and be benignly cleared from the body, enabling a natural reconstruction of the arterial wall and restoration of vascular function.[6]
Studies have shown that the most critical period of vessel healing is largely complete by approximately three to nine months.[6][7][8] Therefore, the goal of a bioresorbable or "temporary" stent is to fully support the vessel during this critical period, and then resorb from the body when it is no longer needed.
Base materials
Bioabsorbable scaffolds, or naturally dissolving stents, that have been investigated include base materials that are either metals or polymers. While polymer-based scaffolds had a strong presence at first, they have meanwhile lost some appeal due to safety concerns and focus is now moved towards metallic magnesium-based scaffolds.[9]
Iron stents were shown using an in vivo evaluation method based on the murine abdominal aorta to generate an iron oxide-filled cavity in the vascular wall.[11] This behavior significantly narrowed the lumen and generated a potential site for rupture of the endothelium after stent degradation.[citation needed]
Magnesium-based scaffolds have been approved for use in several countries around the world. The only commercially available magnesium-based scaffold consists of a magnesium alloy, approximately 95% of which resorbs within one year of implantation.[12][13][14] Thousands of commercially available magnesium-based scaffolds have been implanted. Promising clinical results suggest that magnesium-based scaffolds seem to be a viable option in delivering against the drawbacks of permanent stents.[15][16][17][18] While degrading harmlessly, it has been shown to possess a functional degradation time of about 30 days in vivo. This is much short of the three-to-six month window desired for bioabsorbable stents. Thus, much attention has been given to drastically reducing the rate of magnesium corrosion by alloying, coating, etc.[19] Many novel methods have surfaced to minimize the penetration rate and hydrogen evolution rate (or, in layman's terms, the
corrosion rate). One of the most successful has involved the creation of
bioabsorbable metallic glasses via rapid solidification. Other, alternative solutions have included the development of magnesium–
rare-earth (Mg-RE) alloys, which benefit from the low
cytotoxicity of RE elements.
Coatings and sophisticated materials processing routes are currently being developed to further decrease the corrosion rate. However a number of issues remain limiting the further development of Mg biomaterials in general.[20]
Recently,
zinc was shown to exhibit outstanding physiological corrosion behavior, meeting a benchmark penetration rate of 20 micrometers per year.[21] Although, Pure Zn has poor mechanical behavior, with a tensile strength of around 100–150 MPa and an elongation of 0.3–2%, which is far from reaching the strength required as an orthopedic implant or stent material.[22] this material is relatively new, so further work is required to prove that zinc is a feasible base material for a stent.[citation needed]
Polymer-based
Polymer-based stents have been approved for use in some countries around the world. These are based on poly(L-lactide) (
PLLA), chosen because it is able to maintain a radially strong scaffold that breaks down over time into lactic acid, a naturally occurring molecule that the body can use for metabolism. Other polymers in development include tyrosine poly carbonate and salicylic acid.[23]
An example of a naturally dissolving stent is the 'Absorb' stent 'produced by
Abbott[24] that has several design components and features: base scaffold: a poly(L-lactide) polymer similar to that in dissolvable stitches is shaped into a tube made up of zigzag hoops linked together by bridges; drug-eluting layer': a mixture of poly-D, L-lactide (PDLLA) and everolimus; 'markers': a pair of radio-opaque platinum markers at the ends that allow the device to be visualized during angiography; 'delivery system': a balloon delivery system.[citation needed]
Recently however, Polymer-based scaffolds, in particular Poly-L-Lactide Acid (PLLA) scaffolds, have raised serious concerns on the scaffold performance particularly in terms of safety which led to the commercial discontinuation of the main representative Absorb.[25][26]
Clinical research
Clinical research has shown that resorbable scaffolds, or naturally dissolving stents, offer comparable efficacy and safety profile to drug-eluting stents. Specifically, the Magmaris resorbable magnesium scaffold[27] has reported a favorable safety profile with low target lesion failure and scaffold thrombosis rates. These clinical results are comparable to thin-strutted drug-eluting stents in similar patient populations.[28][29][30][31]
The Absorb naturally dissolving stent has also been investigated in single-arm trials and in randomized trials comparing it to a
drug-eluting stent. Early and late major adverse cardiac events, revascularizations, and scaffold thromboses have been uncommon and similar to the Xience DES, a market leader in the drug eluting stent category.[32][33][34][35][36] Studies in real-world patients are ongoing.[36]
Imaging studies show that the Absorb naturally dissolving stent begins to dissolve from six to 12 months and is fully dissolved between two and three years after it is placed in the artery.[34] Two small platinum markers remain to mark the location of the original PCI. The artery is able to dilate and contract, called vasomotion, similar to a healthy blood vessel at two years.[33]
History
In the US, the first fully absorbable stent was approved by FDA in 2016.[1]
^Serruys PW, Ormiston JA, Onuma Y, et al. (14 March 2009). "A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods". Lancet. 373 (9667): 897–910.
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^Ormiston JA, Serruys PW, Regar E, et al. (15 March 2008). "A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial". Lancet. 371 (9616): 899–907.
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^Biodegradable Metal Stents: A Focused Review on
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^Pierson D, Edick J, Tauscher A, Pokorney E, Bowen PK, Gelbaugh JA, Stinson J, Getty H, Lee CH, Drelich J, Goldman J (January 2012). "A simplified in vivo approach for evaluating the bioabsorbable behavior of candidate stent materials". J Biomed Mater Res B. 100B (1): 58–67.
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^Haude M, Erbel R, Erne (2016). "Safety and performance of the Drug-Eluting Absorbable Metal Scaffold (DREAMS) in patients with de novo coronary lesions: 3-year results of the prospective, multicenter, first-in-man BIOSOLVE-I trial". EuroIntervention. 12 (2): e160-6.
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^Haude M (September 22, 2018). "Imaging and Clinical Results with the latest Magmaris Magnesium-Based Scaffold". Presented at TCT.
^Haude M, Ince H, Abizaid A (May 23, 2018). "Long-term clinical data and multimodality imaging analysis of the BIOSOLVE-II study with the drug-eluting absorbable metal scaffold in the treatment of subjects with de novo lesions in native coronary arteries – BIOSOLVE-II". Presented at EuroPCR.
^Haude M, Erbel R, Erne (2016). "Safety and performance of the Drug-Eluting Absorbable Metal Scaffold (DREAMS) in patients with de novo coronary lesions: 3-year results of the prospective, multicenter, first-in-man BIOSOLVE-I trial". EuroIntervention. 12 (2): e160-6.
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^Li N, Zheng Y (2013). Novel magnesium alloys developed for biomedical application: a review.
ISBN978-3-319-02123-2. {{
cite book}}: |journal= ignored (
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^Kong L, Heydari Z, Lami GH, Saberi A, Baltatu MS, Vizureanu P. A comprehensive review of the current research status of biodegradable zinc alloys and composites for biomedical applications. Materials. 2023 Jul 3;16(13):4797.
https://www.mdpi.com/1996-1944/16/13/4797
^Meredith I, Verheye S, Weissmann N, et al. (2013). "Six-month IVUS and two-year clinical outcomes in the EVOLVE FHU trial: a randomised evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting stent". EuroIntervention. 9 (3): 308–15.
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^Haude M, Ince H, Abizaid A, et al. (May 23, 2018). "Long-term clinical data and multimodality imaging analysis of the BIOSOLVE-II study with the drug-eluting absorbable metal scaffold in the treatment of subjects with de novo lesions in native coronary arteries – BIOSOLVE-II". Presented at EuroPCR.
^Ormiston JA, Serruys PW, Regar E, et al. (2008). "A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial". Lancet. 371 (9616): 899–907.
doi:
10.1016/S0140-6736(08)60415-8.
PMID18342684.
S2CID22926070. 18342684.
^
abSerruys PW, Ormiston JA, Onuma Y, et al. (2009). "A bioabsorbable everolimus-eluting coronary stent system (ABSORB): 2-year outcomes and results from multiple imaging methods". Lancet. 373 (9667): 897–910.
doi:
10.1016/S0140-6736(09)60325-1.
PMID19286089.
S2CID20650067.
^
abSerruys PW, Onuma Y, Garcia-Garcia HM, et al. (2014). "Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months". EuroIntervention. 9 (11): 1271–1284.
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^Serruys PW, Chevalier B, Dudek D, et al. (2015). "A bioresorbable everolimus-eluting scaffold versus a metallic everolimus-eluting stent for ischaemic heart disease caused by de-novo native coronary artery lesions (ABSORB II): an interim 1-year analysis of clinical and procedural secondary outcomes from a randomised controlled trial". Lancet. 385 (9962): 43–54.
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^
abSmits P, Ziekenhuis M, Absorb Extend: an interim report on the 36-month clinical outcomes from the first 250 patients enrolled. Presented at Transcatheter Cardiovascular Therapeutics (TCT) conference 2014 in Washington, DC, September 2014