3D-printed Bioresorbable Stent Coated with Dipyridamole-Loaded Nanofiber for Restenosis Prevention and Endothelialization
Intimal hyperplasia and restenosis caused by excessive proliferation of smooth muscle cells (SMC) are the main factors for the failure of stent implantation. Drug-eluting stents carried with antiproliferative drugs have emerged as a successful approach to alleviate early neointimal development. However, these agents have been reported to have an undesirable effect on re-endothelialization. In this study, we proposed an integrated bioresorbable stent coated with dipyridamole (DP)- loaded poly(D,L-lactide) (PDLLA) nanofibers. Three-dimensional (3D) bioresorbable stents were fabricated by printing on a rotation mandrel using polycaprolactone (PCL), and the stents were further coated with PDLLA/DP nanofibers. The in vitro degradation and drug release evaluation illustrated the potential for long-term release of DP. Stents coated with PDLLA/DP nanofibers showed excellent hemocompatibility. The cell viability, proliferation, and morphology analysis results revealed that stents coated with PDLLA/DP nanofibers could prevent the proliferation of SMC and have no adverse effects on endothelial cells. The in vivo implantation of stents coated with PDLLA/DP nanofibers showed initial patency and continuous endothelialization and alleviated neointimal formation. The attractive in vitro and in vivo performance indicated its potential for restenosis prevention and endothelialization.
1. Wiebe J, Nef HM, Hamm CW, 2014, Current Status of Bioresorbable Scaffolds in the Treatment of Coronary Artery Disease. J Am Coll Cardiol, 64:2541–51. https://doi.org/10.1016/j.jacc.2014.09.041
2. Wessely R, 2010, New Drug-eluting Stent Concepts. Nat Rev Cardiol, 7:194–203. https://doi.org/10.1038/nrcardio.2010.14
3. Ang H Y, Bulluck H, Wong P, et al., 2017, Bioresorbable Stents: Current and Upcoming Bioresorbable Technologies. Int J Cardiol, 228:931–9. https://doi.org/10.1016/j.ijcard.2016.11.258
4. Joner M, Finn AV, Farb A, et al., 2006, Pathology of Drug-Eluting Stents in Humans. Delayed Healing and Late Thrombotic Risk. J Am Coll Cardiol, 48:193–202. https://doi.org/10.1016/j.jacc.2006.03.042
5. Capranzano P, Dangas G, 2012, Late Stent Thrombosis: The Last Remaining Obstacle in Coronary Interventional Therapy. Curr Cardiol Rep, 14:408–17. https://doi.org/10.1007/s11886-012-0283-9
6. Inoue T, Croce K, Morooka T, et al., 2011, Vascular Inflammation and Repair: Implications for Reendothelialization, Restenosis, and Stent Thrombosis. JACC: Cardiovasc Interv, 4:1057–66. https://doi.org/10.1016/j.jcin.2011.05.025
7. Jinnouchi H, Torii S, Sakamoto A, et al., 2019, Fully bioresorbable vascular scaffolds: lessons learned and future directions. Nat Rev Cardiol, 16:286–304. https://doi.org/10.1038/s41569-018-0124-7
8. Onuma Y, Ormiston J, Serruys PW, 2011, Bioresorbable Scaffold Technologies. Circ J, 75:509–20. https://doi.org/10.1253/circj.CJ-10-1135
9. Iqbal J, Onuma Y, Ormiston J, et al., 2014, Bioresorbable Scaffolds: Rationale, Current Status, Challenges, and Future. Eur Heart J, 35:765–76. https://doi.org/10.1093/eurheartj/eht542
10. Toong DW, Ng JC, Huang Y, et al., 2020, Bioresorbable Metals in Cardiovascular Stents: Material Insights and Progress. Materialia, 12:100727. https://doi.org/10.1016/j.mtla.2020.100727
11. Wang C, Zhang L, Fang Y, et al., 2021, Design, Characterization, and 3D Printing of Cardiovascular Stents with Zero Poisson’s Ratio in Longitudinal Deformation. Engineering, 7:979–90. https://doi.org/10.1016/j.eng.2020.02.013
12. Zhuplatov SB, Masaki T, Blumenthal DK, et al., 2006, Mechanism of Dipyridamole’s Action in Inhibition of Venous and Arterial Smooth Muscle Cell Proliferation. Basic Clin Pharmacol Toxicol, 99:431–9. https://doi.org/10.1111/j.1742-7843.2006.pto_516.x
13. Mattfeldt T, Mall G, 1983, Dipyridamole-induced Capillary Endothelial Cell Proliferation in the Rat Heart a Morphometric Investigation. Cardiovasc Res, 17:229–37. https://doi.org/10.1093/cvr/17.4.229
14. Lamichhane S, Gallo A, Mani G, 2014, A Polymer-free Paclitaxel Eluting Coronary Stent: Effects of Solvents, Drug Concentrations and Coating Methods. Ann Biomed Eng, 42:1170–84. https://doi.org/10.1007/s10439-014-1003-y
15. Chen MC, Liang HF, Chiu YL, et al., 2005, A Novel Drug eluting Stent Spray-coated with Multi-layers of Collagen and Sirolimus. J Control Release, 108:178–89. https://doi.org/10.1016/j.jconrel.2005.07.022
16. Huang Y, Subbu SS, Boey FY, et al., 2010, In vitro and In vivo Performance of a Dual Drug-eluting Stent (DDES). Biomaterials, 31:4382–91. https://doi.org/10.1016/j.biomaterials.2010.01.147
17. Oh Band Lee CH, 2013, Advanced Cardiovascular Stent Coated with Nanofiber. Mol Pharm, 10:4432–42. https://doi.org/10.1021/mp400231p
18. Tan GZ, Zhou Y, 2019, Electrospinning of Biomimetic Fibrous Scaffolds for Tissue Engineering: A Review. Int J Polym Mater Polym Biomater, 69:947–60. https://doi.org/10.1080/00914037.2019.1636248
19. Oh B, Lee CH, 2013, Nanofiber for Cardiovascular Tissue Engineering. Expert Opin Drug Deliv, 10:1565–82.
20. Hu X, Liu S, Zhou G, et al., 2014, Electrospinning of Polymeric Nanofibers for Drug Delivery Applications. J Control Release, 185:12–21. https://doi.org/10.1016/j.jconrel.2014.04.018
21. Punnakitikashem P, Truong D, Menon JU, et al., 2014, Electrospun Biodegradable Elastic Polyurethane Scaffolds with Dipyridamole Release for Small Diameter Vascular Grafts. Acta Biomater, 10:4618–28. https://doi.org/10.1016/j.actbio.2014.07.031
22. Liu P, Liu Y, Li P, et al., 2018, Rosuvastatin-and Heparin-Loaded Poly (l -lactide- co-caprolactone) Nanofiber Aneurysm Stent Promotes Endothelialization via Vascular Endothelial Growth Factor Type A Modulation. ACS Appl Mater Interf, 10:41012-41018. https://doi.org/10.1021/acsami.8b11714
23. Wang C, Xu Y, Xia J, et al., 2021, Multi-scale Hierarchical Scaffolds with Aligned Micro-fibers for Promoting Cell Alignment. Biomed Mater (Bristol), 16:ac0a90. https://doi.org/10.1088/1748-605X/ac0a90
24. Lin S, Ran X, Yan X, et al., 2019, Corrosion Behavior and Biocompatibility Evaluation of a Novel Zinc-based Alloy Stent in Rabbit Carotid Artery Model. J Biomed Mater Res Part B Appl Biomater, 107:1814–1823. https://doi.org/10.1002/jbm.b.34274
25. Im SH, Kim CY, Jung Y, et al., 2017, Biodegradable Vascular Stents with High Tensile and Compressive Strength: A Novel Strategy for Applying Monofilaments Via Solid state Drawing and Shaped-annealing Processes. Biomater Sci, 5:422–31. https://doi.org/10.1039/c7bm00011a
26. Xue J, Wu T, Dai Y, et al., 2019, Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem Rev, 119:5298–415. https://doi.org/10.1021/acs.chemrev.8b00593
27. Fong H, Chunand I, Reneker DH, 1999, Beaded Nanofibers Formed during Electrospinning. Polymer, 40:4585–92.
28. Qin Y, Liu R, Zhao Y, et al., 2016, Preparation of Dipyridamole/Polyurethane Core-shell Nanofibers by Coaxial Electrospinning for Controlled-release Antiplatelet Application. J Nanosci Nanotechnol, 16:6860–6. https://doi.org/10.1166/jnn.2016.11386
29. Repanas A, Wolkers WF, Gryshkov OP, et al., 2015, Pcl/Peg Electrospun Fibers as Drug Carriers for the Controlled Delivery of Dipyridamole. J In Silico In vitro Pharmacol, 1:1–10. https://doi.org/10.21767/2469-6692.10003
30. Ruggeri ZM, Mendolicchio GL, 2007, Adhesion Mechanisms in Platelet Function. Circ Res, 100:1673–85. https://doi.org/10.1161/01.RES.0000267878.97021.ab
31. Li W, Zhou J, Xu Y, 2015, Study of the In vitro Cytotoxicity Testing of Medical Devices. Biomed Rep, 3:617–20. https://doi.org/10.3892/br.2015.481
32. 10993-5:2009 I, Biological Evaluation of Medical Devices Part 5: Tests for In vitro Cytotoxicity. Technical Committee.
33. Wu X, Wu S, Kawashima H, et al., 2021, Current Perspectives on Bioresorbable Scaffolds in Coronary Intervention and other Fields. Expert Rev Med Dev, 18:351–65. https://doi.org/10.1080/17434440.2021.1904894
34. Woodruff MA, Hutmacher DW, 2010, The Return of a Forgotten Polymer Polycaprolactone in the 21st Century. Prog Polym Sci (Oxford), 35:1217–56. https://doi.org/10.1016/j.progpolymsci.2010.04.002
35. Kim K, Yu M, Zong X, et al., 2003, Control of Degradation Rate and Hydrophilicity in Electrospun Non-woven Poly (D,L-lactide) Nanofiber Scaffolds for Biomedical Applications. Biomaterials, 24:4977–85. https://doi.org/10.1016/S0142-9612(03)00407-1
36. Ulery BD, Nair LS, Laurencin CT, 2011, Biomedical Applications of Biodegradable Polymers. J Polym Sci Part B Polym Phys, 49:832–64. https://doi.org/10.1002/polb.22259
37. Repanas A, Glasmacher B, 2015, Dipyridamole Embedded in Polycaprolactone Fibers Prepared by Coaxial Electrospinning as a Novel Drug Delivery System. J Drug Deliv Sci Technol, 29:132–42. https://doi.org/10.1016/j.jddst.2015.07.001
38. Qiu T, Jiang W, Yan P, et al., 2020, Development of 3D-Printed Sulfated Chitosan Modified Bioresorbable Stents for Coronary Artery Disease. Front Bioeng Biotechnol, 8:462. https://doi.org/10.3389/fbioe.2020.00462
39. Lei D, Luo B, Guo Y, et al., 2019, 4-Axis Printing Microfibrous Tubular Scaffold and Tracheal Cartilage Application. Sci China Mater, 62:1910–20. https://doi.org/10.1007/s40843-019-9498-5
40. Martinez-Lemus LA, 2012, The Dynamic Structure of Arterioles. Basic Clin Pharmacol Toxicol, 110:5–11. https://doi.org/10.1111/j.1742-7843.2011.00813.x