Platelet deposition on stainless steel, spiral, and braided polylactide stents

Summary

Platelets play a key role in (sub)acute thrombotic occlusion after stenting. We examined the possible differences between biodegradable polylactide (PLA) and stainless steel (SS) stents in platelet attachment and morphology after whole blood perfusion. PLA stents of different configurations (spiral/braided) and polycaprolactone-polylactide (PCL-PLA)-coatings, or SS stents were implanted into a PVC tube (Ø 3.2 mm), with or without precoating of the tube with type-I collagen. PPACK (30 µM)-anticoagulated blood with 3H-serotonin prelabeled platelets was perfused (flow rate: 30 ml/min, 90 s) over the stents. Platelet deposition was assessed by scintillation counting and morphology by scanning electron microscopy (SEM). To examine coagulation activation, plasma prothrombin fragments (F1+2) were measured before and after the perfusion. Protein deposition on PLA/SS stents was assessed at augmented shear forces mimicking coronary flow (rate: 60 ml/min, 60 s) under minimal anticoagulation (PPACK 1 µM). More platelets deposited on PLA stents than on SS stents under all study conditions (p <0.03). Under anticoagulation (PPACK 30 µM) the generation of F1+2 remained unaltered. Under higher flow rate and limited anticoagulation SS stents accumulated 3.27 ± 0.75 µg and PLA stents 5.25 ± 1.74 µg of protein (Mean ± SD, p <0.95). Among all biodegradable stents, the braided PLA stent coated with PCL-PLA-heparin accumulated the fewest platelets (p <0.02). In SEM, signs of platelet activation on braided heparin-coated PLA stents, when compared with uncoated braided PLA/SS stents, appeared modest. In conclusion, PCL-PLAheparin coating of biodegradable stents may enhance their hemocompatibility, expressed by less platelet deposition. Nevertheless, materials, design, and coating techniques of biodegradable stents must be further developed.

Keywords

Stent - vascular - thrombosis - heparin - polylactide

• References

• 1 Holmes Jr DR. et al. ACC expert consensus document on coronary artery stents. J Am Coll Cardiol 1998; 32: 1471-82.
• 2 The SoS Investigators. Coronary artery bypass surgery versus percutaneous coronary intervention with stent implantation in patients with multivessel coronary artery disease (the Stent or Surgery trial): a randomized controlled trial. Lancet 2002; 360: 965-70.
• 3 De Feyter PJ, Serruys PW, Unger F. et al. Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina. Circulation 2002; 105: 2367-72.
• 4 Bahapulle MN, Eisenberg MJ. Coated stents for the prevention of restenosis: part II. Circulation 2002; 106: 2859-66.
• 5 Grube E, Silber S, Hauptmann KE. et al. TAXUS I Sixand twelve-month results from a randomized, double-blind trial on a slowrelease paclitaxel-eluting stent for de novo coronary lesions. Circulation 2003; 107: 38-42.
• 6 Degertekin M, Serruys PW, Foley DP. et al. Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation Long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound followup. Circulation 2002; 106: 1610-13.
• 7 Gawaz M, Neumann FJ, Ott I. et al. Role of activation-dependent platelet membrane glycoproteins in development of subacute occlusive coronare stent thrombosis. Coron Artery Dis 1997; 08: 121-8.
• 8 Orford JL. et al. Frequency and correlates of coronary stent thrombosis in the modern era Analysis of a single center registry. J Am Coll Cardiol 2002; 40: 1567-72.
• 9 Shih CC, Shih CM, Chen YL. et al. Growth inhibition of cultured smooth muscle cells by corrosion products of 316 L stainless steel wire. J Biomed Mater Res 2001; 57: 200-7.
• 10 Hårdhammar PA, van Beusekom HMM, Emanuelsson HU. et al. Reduction in thrombotic events with heparin-coated PalmazSchatz stents in normal porcine coronary arteries. Circulation 1996; 93: 423-30.
• 11 De Scheerder I. et al. Experimental study of thrombogenicity and foreign body reaction induced by heparin-coated coronary stents. Circulation 1997; 95: 1549-53.
• 12 Blezer R. et al. Heparin coating of tantalum coronary stents reduces surface thrombin generation but not factor IXa generation. Blood Coagul Fibrinolysis 1998; 09: 435-40.
• 13 Vrolix MMC. et al. the MENTOR trial investigators Heparin-coated Wiktor stents in human coronary arteries (MENTOR trial). Am J Cardiol 2000; 86: 385-9.
• 14 Wohrle J, Al-Khayer E, Grotzinger U. et al. Comparison of the heparin coated vs the uncoated Jostent-no influence on restenosis or clinical outcome. Eur Heart J 2001; 22: 1766-8.
• 15 Haude M, Konorza FM, Kalnins Y. et al. heparin-COAted STents in small coronary arteries (COAST) trial investigators Heparin-coated stent placement for the treatment of stenoses in small coronary arteries of symptomatic patients. Circulation 2003; 107: 1265-70.
• 16 Matsumoto Y, Shimokawa H, Morishige K. et al. Reduction in neointimal formation with a stent coated with multiple layers of releasable heparin in porcine coronary arteries. J Cardiovasc Pharmacol 2002; 39: 513-22.
• 17 Peter K, Schwarz M, Conradt C. et al. Heparin inhibits ligand binding to the leucocyte integrin Mac-1 (CD11b/CD18). Circulation 1999; 100: 1533-9.
• 18 Athanasiou KA. et al. Orthopaedic applications of PLAPGA biodegradable polymers. Arthroscopy 1998; 14: 726-37.
• 19 Peltoniemi H. Biocompatibility and fixation properties of absorbable miniplates and screws in growing calvarium. Doctoral thesis. University of Helsinki; Finland: 2000
• 20 Zidar J, Lincoff A, Stack R. Biodegradable stents. In: Topol L) Textbook of Interventional Radiology. 2 nd edn, 1994. Saunders; Philadelphia: 787-802.
• 21 Hietala EM, Salminen US, Ståhls A. et al. Biodegradation of the copolymeric polylactide stent Long-term follow-up in a rabbit aorta model. J Vasc Res 2001; 38: 361-9.
• 22 Korpela A, Aarnio P, Sariola H, Törmälä P, Harjula A. Bioabsorbable self-reinforced poly-l-lactide, metallic, and silicone stents in the management of experimental tracheal stenosis. Chest 1999; 115: 490-5.
• 23 Parviainen M, Sand J, Harmoinen A. et al. A new biodegradable stent for the pancreatico-jejunal anstomosis after pancreaticoduodenal resection: in vitro examination and pilot experiences in humans. Pancreas 2000; 21: 14-21.
• 24 Petas A, Talja M, Tammela TL. et al. The biodegradable self-reinforced poly-DL-lactic acid spiral stent compared with suprapubic catheter in the treatment of post-operative urinary retention after visual laser ablation of the prostate. Br J Urol 1997; 80: 439-43.
• 25 van der Giessen WJ. et al. Marked inflammatory sequelae to implantation of biodegradable polymers in porcine coronary artery. Circulation 1996; 94: 1690-7.
• 26 Lincoff AM, Furst JG, Ellis SG. et al. Sustained local delivery of dexametasone by a novel intravascular stent to prevent restenosis in the porcine coronary injury model. J Am Coll Cardiol 1997; 29: 808-16.
• 27 Su SH, Chao RY, Landau CL. et al. Expandable bioresorbable endovascular stent Fabrication and properties. Ann Biomed Eng 2003; 31: 667-77.
• 28 Yamawaki T, Shimokawa H, Kozai T. et al. Intramural delivery of a specific tyrosine kinase inhibitor with biodegradable stent suppresses the restenotic changes of the coronary artery in pigs in vivo . J Am Coll Cardiol 1998; 32: 780-6.
• 29 Tamai H, Igaki K, Kyo E. et al. Initial and 6month results of biodegradable poly-l-lactic acid stents in humans. Circulation 2000; 102: 399-404.
• 30 Seifert B, Groth TH, Herrmann K. et al. Immobilization of heparin on polylactide for application to degradable biomaterials in contact with blood. J Biomater Sci Polymer Edn 1995; 07: 277-87.
• 31 Mustonen P, Lassila R. Epinephrine augments platelet recruitment to immobilized collagen in flowing blood - evidence for a von Willebrand factor -mediated mechanism. Thromb Haemost 1996; 75: 175-81.
• 32 Hietala EM, Maasilta P, Välimaa T. et al. Platelet responses and coagulation acivation on polylactide and heparin-polycaprolactoneL-lactide coated polylactide. J Biomed Mater Res 2003; 67A: 78591.
• 33 Gurbel PA, Callahan KP, Malinin AI. et al. Could stent design affect platelet activation? Results of the Platelet Activation in Stenting (PAST) study. J Invasive Cardiol 2002; 14: 584-9.
• 34 Siljander P, Carpen O, Lassila R. Plateletderived microparticles associate with fibrin during thrombosis. Blood 1996; 87: 4651-63.
• 35 Heemskerk JW, Siljander PR, Bevers EM. et al. Receptors and signaling mechanisms in the procoagulant response of platelets. Platelets 2000; 11: 301-6.
• 36 Nguyen K, Su S-H, Sheng A. et al. In vitro hemocompatibility studies of drug-loaded poly-(L-lactic acid) fibers. Biomaterials 2003; 24: 5191-201.
• 37 Alt E, Hähnel I. et al. Inhibition of neointima formation after experimental coronary artery stenting: a new biodegradable stent coating releasing hirudin and the prostacyclin analogue iloprost. Circulation 2000; 101: 1453-8.
• 38 Herrmann R, Schmidmaier G, Märkl B. et al. Antithrombogenic coating of stents using a biodegradable drug delivery technology. Thromb Haemost 1999; 82: 51-7.
• 39 Schwartz RS, Holder DJ, Holmes DR. et al. Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor: results in a porcine model. Circulation 1996; 93: 1542-8.
• 40 Unterberg C. et al. Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty. J Am Coll Cardiol 1995; 26: 1747-54.
• 41 Tsuchikane E, Fukuhara A, Kabayashi T. et al. Impact of ciclostazol on restenosis after percutaneous balloon angioplasty. Circulation 1999; 100: 21-6.
• 42 De Scheerder I. et al. Experimental study of thrombogenecity and foreign body reaction induced by heparin-coated coronary stents. Circulation 1997; 95: 1549-53.
• 43 The ERASER investigators. Acute platelet inhibition with abciximab does not reduce instent restenosis (ERASER study). Circulation 1999; 100: 799-806.
• 44 Kauhanen P, Kovanen PT, Lassila R. Coimmobilized native macromolecular heparin proteoglycans strongly inhibit platelet-collagen interactions in flowing blood. Arterioscler Thromb Vasc Biol 2000; 20: e113-e119.
• 45 Olsson E, Asko-Seljavaara S, Lassila R. Topically administered macromolecular heparin proteoglycans inhibit thrombus growth in microvascular anastomoses. Thromb Haemost 2002; 87: 245-51.
• 46 Azrin MA, Mitchel JF, Fram DB. et al. Angioplasty/Atherectomy: Decreased platelet deposition and smooth muscle cell proliferation after intramural heparin delivery with hydrogel-coated balloons. Circulation 1994; 90: 433-41.
• 47 Andersson J, Sanchez J, Ekdahl K. et al. Optimal heparin surface consentration and antithrombin binding capacity as evaluated with human non-anticoagulated blood in vitro . J Biomed Mater Res 2003; 67A: 458-66.
• 48 Blezer R. et al. Activation of blood coagulation at heparin-coated surfaces. J Biomater Res 1997; 37: 108-13.
• 49 Van Delden CJ, Engbers GHM, Feijen J. The effect of protein absorption on the anticoagulant activity of surface immobilized heparin. J Biometr Sci Polymer Edn 1996; 07: 727-40.
• 50 Mehran R, Aymong ED, Ashby DT. et al. Safety of an asperin-alone regimen after intracoronary stenting with a heparin-coated stent Final results of the HOPE. (HEPACOAT and an antithrombotic regimen of aspirin alone) study. Circulation 2003; 108: 1078-83.