Development of a sirolimus-eluting poly (l-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention
-
Niels Grabow
, Carsten M. Bünger
, Sabine Kischkel , J. Hinrich Timmermann , Thomas Reske , David P. Martin , Simon F. Williams , Wolfgang Schareck , Katrin Sternberg und Klaus-Peter Schmitz
Abstract
Fully absorbable drug-eluting stent platforms are currently entering the clinical arena for the interventional treatment of coronary artery disease. This new technology also holds potential for application in peripheral vascular settings. Our study reports on the development of a sirolimus- (SIR) eluting absorbable polymer stent made from a blend of poly(l-lactide) and poly(4-hydroxybutyrate) (PLLA/P4HB) for peripheral vascular intervention. Stent prototypes were laser-cut from PLLA/P4HB tubes (I.D.=2.2 mm, t=250 µm), spray-coated with different PLLA/P4HB/SIR solutions, and bench-tested to determine expansion properties, fatigue, trackability and in vitro drug release kinetics. The stent prototypes were expanded with a 5.0×20 mm balloon catheter, and exhibited a recoil of 3.6% upon balloon deflation. Stent collapse pressure of 0.4 bar (300 mm Hg) was measured under external pressure load. Sustained scaffolding properties were observed in vitro over 14 weeks of radial fatigue loading (50±25 mm Hg at 1.2 Hz). Trackability was demonstrated in bench tests with an 8 French contralateral introducer sheath. SIR release kinetics were adjusted over a broad range by varying the PLLA/P4HB ratio of the coating matrix. The newly developed absorbable SIR-eluting PLLA/P4HB stent successfully fulfilled the requirements for peripheral vascular intervention under in vitro conditions.
Partial financial support was provided from the European Regional Development Fund (ERDF) and the European Social Fund (ESF) within the joint research program between business and academia in Mecklenburg-Vorpommern, as well as from the German Ministry for Education (BMBF) for the collaborative research project “REMEDIS – Höhere Lebensqualität durch neuartige Mikroimplantate” within the program “Spitzenforschung und Innovation in den Neuen Ländern”.
Dipl.-Ing. Peter Behrens and Dr.-Ing. Wolfram Schmidt, Institute for Biomedical Engineering, University of Rostock, are gratefully acknowledged for sharing their expertise in stent testing.
References
[1] Biamino G, Schmidt A, Scheinert D. Treatment of SFA lesions with PLLA biodegradable stents: results of the PERSEUS study. J Endovasc Ther 2005; 12(Suppl. I): I–5.Suche in Google Scholar
[2] Bosiers M, Peeters P, D’Archambeau O, et al. AMS INSIGHT – absorbable metal stent implantation for treatment of below-the-knee critical limb ischemia: 6-month analysis. Cardiovasc Intervent Radiol 2009; 32: 424–435.10.1007/s00270-008-9472-8Suche in Google Scholar
[3] Brown DA, Lee EW, Loh CT, Kee ST. A new wave in treatment of vascular occlusive disease: biodegradable stents – clinical experience and scientific principles. J Vasc Interv Radiol 2009; 20: 315–324.10.1016/j.jvir.2008.11.007Suche in Google Scholar
[4] Bünger CM, Grabow N, Kröger C, et al. Iliac anastomotic stenting with a sirolimus-eluting biodegradable poly-L-lactide stent: a preliminary study after 6 weeks. J Endovasc Ther 2006; 13: 630–639.10.1583/06-1899R.1Suche in Google Scholar
[5] Bünger CM, Grabow N, Sternberg K, et al. Sirolimus-eluting biodegradable poly-l-lactide stent for peripheral vascular application: a preliminary study in porcine carotid arteries. J Surg Res 2007; 139: 77–82.10.1016/j.jss.2006.07.035Suche in Google Scholar
[6] Chichkov B, Momma C, Nolte S, von Alvensleben F, Tunnermann A. Femtosecond, picosecond and nanosecond laser ablation of solids. Appl Phys A 1996; 63: 109–115.10.1007/BF01567637Suche in Google Scholar
[7] Colombo A, Hall P, Nakamura S, et al. Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. Circulation 1995; 91: 1676–1688.10.1161/01.CIR.91.6.1676Suche in Google Scholar
[8] Dudek D, Onuma Y, Ormiston JA, Thuesen L, Miquel-Hebert K, Serruys PW. Four-year clinical follow-up of the ABSORB everolimus-eluting bioresorbable vascular scaffold in patients with de novo coronary artery disease: the ABSORB trial. EuroIntervention 2012; 7: 1060–1061.10.4244/EIJV7I9A168Suche in Google Scholar
[9] Erbel R, Di Mario C, Bartunek J, et al. Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial. Lancet 2007; 369: 1869–1875.10.1016/S0140-6736(07)60853-8Suche in Google Scholar
[10] Grabow N, Bunger C, Sternberg K, Mews S, Schmohl K, Schmitz KP. Mechanical properties of a biodegradable balloon-expandable stent from poly(L-lactide) for peripheral vascular applications. ASME J Med Devices 2007; 1: 84–88.10.1115/1.2355683Suche in Google Scholar
[11] Grabow N, Bünger CM, Schultze C, et al. A biodegradable slotted tube stent based on poly(L-lactide) and poly(4-hydroxybutyrate) for rapid balloon-expansion. Ann Biomed Eng 2007; 35: 2031–2038.10.1007/s10439-007-9376-9Suche in Google Scholar PubMed
[12] Grabow N, Schmitt L, Pfensig S, et al. Spray-coating process development, manufacture, quality assessment and drug release behavior of peripheral drug-eluting stents. Biomed Tech (Berl) 2012 Sep 6. DOI:10.1515/bmt-2012-4298.10.1515/bmt-2012-4298Suche in Google Scholar
[13] Holmes DR Jr., Moses JW, Schofer J, Morice MC, Schampaert E, Leon MB. Cause of death with bare metal and sirolimus-eluting stents. Eur Heart J 2006; 27: 2815–2822.10.1093/eurheartj/ehl385Suche in Google Scholar PubMed
[14] Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006; 48: 193–202.10.1016/j.jacc.2006.03.042Suche in Google Scholar PubMed
[15] Onuma Y, Serruys PW. Bioresorbable scaffold: the advent of a new era in percutaneous coronary and peripheral revascularization? Circulation 2011; 123: 779–797.10.1161/CIRCULATIONAHA.110.971606Suche in Google Scholar PubMed
[16] Ormiston JA, Webster MW, Armstrong G. First-in-human implantation of a fully bioabsorbable drug-eluting stent: the BVS poly-L-lactic acid everolimus-eluting coronary stent. Catheter Cardiovasc Interv 2006; 69: 128–131.10.1002/ccd.20895Suche in Google Scholar PubMed
[17] Schmidt W, Schmitz KP. Devices. In: Lanzer P, editor. Mastering of endovascular techniques – A guide to excellence. Philadelphia: Lippincott Williams & Wilkins 2006: 114–135.Suche in Google Scholar
[18] Schmidt W, Andresen R, Behrens P, Schmitz KP. Characteristic mechanical properties of balloon-expandable peripheral stent systems. Rofo-Fortschr Rontg 2002; 174: 1430–1437.10.1055/s-2002-35345Suche in Google Scholar PubMed
[19] Schmidt W, Schmitz KP, Behrens P, Behrend D, Lootz D. Is a standardized measurement of the elastic recoil of coronary stents under vascular conditions necessary and meaningful? Prog Biomed Res 2000; 5: 204–210.Suche in Google Scholar
[20] Standard Guide for Measuring Securement of Balloon Expandable Vascular Stent Mounted on Delivery System. ASTM F2394–07 (2013).Suche in Google Scholar
[21] Tamai H, Igaki K, Kyo E, et al. Initial and 6-month results of biodegradable poly-l-lactic acid coronary stents in humans. Circulation 2000; 102: 399–404.10.1161/01.CIR.102.4.399Suche in Google Scholar
[22] Tan LP, Venkatraman SS, Joso JF, Boey FY. Collapse pressures of bilayered biodegradable stents. J Biomed Mater Res B Appl Biomater 2006; 79: 102–107.10.1002/jbm.b.30518Suche in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
Artikel in diesem Heft
- Masthead
- Masthead
- Special issue articles
- Editorial
- Bioresorbable implants
- Review
- Biological heart valves
- Laser microstructured biodegradable scaffolds
- In vivo degradation of magnesium alloy LA63 scaffolds for temporary stabilization of biological myocardial grafts in a swine model
- Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications
- Development of a sirolimus-eluting poly (l-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention
- Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration
- Heart valve engineering: decellularized allograft matrices in clinical practice
- Research Articles
- Effect of microthread design of dental implants on stress and strain patterns: a three-dimensional finite element analysis
- Construction and in vitro test of a new electrode for dentin resistance measurement
- Effects of anthropometric variables and electrode placement on the SEMG activity of the biceps brachii muscle during submaximal isometric contraction in arm wrestling
Artikel in diesem Heft
- Masthead
- Masthead
- Special issue articles
- Editorial
- Bioresorbable implants
- Review
- Biological heart valves
- Laser microstructured biodegradable scaffolds
- In vivo degradation of magnesium alloy LA63 scaffolds for temporary stabilization of biological myocardial grafts in a swine model
- Implant-associated local drug delivery systems based on biodegradable polymers: customized designs for different medical applications
- Development of a sirolimus-eluting poly (l-lactide)/poly(4-hydroxybutyrate) absorbable stent for peripheral vascular intervention
- Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration
- Heart valve engineering: decellularized allograft matrices in clinical practice
- Research Articles
- Effect of microthread design of dental implants on stress and strain patterns: a three-dimensional finite element analysis
- Construction and in vitro test of a new electrode for dentin resistance measurement
- Effects of anthropometric variables and electrode placement on the SEMG activity of the biceps brachii muscle during submaximal isometric contraction in arm wrestling