Skip to main content
SpringerLink
Log in

Aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds: potential small-diameter vascular grafts for thrombosis prevention

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for by-pass procedures. The development of bioresorbable vascular scaffolds with localized and sustained intra-luminal antithrombotic drug release could be considered a desirable improvement towards a valuable solution for this relevant clinical need. For this aim, we present the fabrication and characterization of aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds as a vascular drug-delivery graft. Three different drug concentrations were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was clearly observed for all the collected scaffolds, aspirin content was directly implied in the final microstructure leading to a bimodal fiber diameter distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical response highlighted a direct relationship for modulus and stress at break with the aspirin content, while the elongation at break was not remarkably different for the investigated cases. The temporal drug release was strongly dependent from the amount of loaded aspirin, reaching a steady state release after about 50 h. Finally, the adhesion assay confirmed the capability of the electrospun scaffolds to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers. Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate to develop a novel bioresorbable drug-releasing graft for small-diameter vessel replacements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. European cardiovascular disease statistics. European Heart Network; 2008.

  2. Yusuf S, Ounpuu S, Anand S. The global epidemic of atherosclerotic cardiovascular disease. Med Princ Pract. 2002;11(Suppl 2):3–8.

    Article  Google Scholar 

  3. Hashi CK, Derugin N, Janairo RR, Lee R, Schultz D, Lotz J, Li S. Antithrombogenic modification of small-diameter microfibrous vascular grafts. Arterioscler Thromb Vasc Biol. 2010;30:1621–7.

    Article  CAS  Google Scholar 

  4. Pektok E, Nottelet B, Tille JC, Gurny R, Kalangos A, Moeller M, Walpoth BH. Degradation and healing characteristics of small-diameter poly(ε-caprolactone) vascular grafts in the rat systemic arterial circulation. Circulation. 2008;118:2563–70.

    Article  CAS  Google Scholar 

  5. Nottelet B, Pektok E, Mandracchia D, Tille JC, Walpoth B, Gurny R, Möller M. Factorial design optimization and in vivo feasibility of poly(ε-caprolactone)-micro- and nanofiber-based small diameter vascular grafts. J Biomed Mater Res A. 2009;89:865–75.

    CAS  Google Scholar 

  6. Innocente F, Mandracchia D, Pektok E, Nottelet B, Tille JC, de Valence S, Faggian G, Mazzucco A, Kalangos A, Gurny R, Moeller M, Walpoth BH. Paclitaxel-eluting biodegradable synthetic vascular prostheses, a step towards reduction of neointima formation? Circulation. 2009;120(suppl 11):S37–45.

    Article  CAS  Google Scholar 

  7. Sarkar S, Sales KM, Hamilton G, Seifalian AM. Addressing thrombogenicity in vascular graft construction. J Biomed Mater Res B. 2007;82:100–8.

    Google Scholar 

  8. Jämstorp E, Bodin A, Gatenholm P, Jeppsson A, Strømme M. Release of antithrombotic drugs from alginate gel beads. Curr Drug Deliv. 2010;7:297–302.

    Article  Google Scholar 

  9. Field TS, Benavente OR. Current status of antiplatelet agents to prevent stroke. Curr Neurol Neurosci Rep. 2011;11:6–14.

    Article  CAS  Google Scholar 

  10. CAPRIE steering committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–39.

    Article  Google Scholar 

  11. Badruddin A, Gorelick PB. Antiplatelet therapy for prevention of recurrent stroke. Curr Treat Options Neurol. 2009;11:452–9.

    Article  Google Scholar 

  12. Kral M, Herzig R, Sanak D, Skoloudik D, Vlachova I, Bartkova A, Hlustik P, Kovacik M, Kanovsky P. Oral antiplatelet therapy in stroke prevention. Minireview. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154:203–10.

    Article  CAS  Google Scholar 

  13. Guslandi M. Gastric toxicity of antiplatelet therapy with low-dose aspirin. Drugs. 1997;53:1–5.

    Article  CAS  Google Scholar 

  14. Sztriha LK, Sas K, Vecsei L. Aspirin resistance in stroke: 2004. J Neurol Sci. 2005;229:163–9.

    Article  Google Scholar 

  15. Hall JD, Rittgers SE, Schmidt SP. Effect of controlled local acetylsalicylic acid release on in vitro platelet adhesion to vascular grafts. J Biomater Appl. 1994;8:361–84.

    Article  CAS  Google Scholar 

  16. Guyton AC. Textbook of medical physiology. 7th ed. Philadelphia: W.B. Saunders Co.; 1986.

    Google Scholar 

  17. Wulf K, Teske M, Löbler M, Luderer F, Schmitz KP, Sternberg K. Surface functionalization of poly(ε-caprolactone) improves its biocompatibility as scaffold material for bioartificial vessel prostheses. J Biomed Mater Res B. 2011;98:89–100.

    Google Scholar 

  18. Allen BT, Sparks RE, Welch MJ, Mason NS, Mathias CJ, Clark RE. Reduction of platelet deposition on vascular grafts using an antiplatelet graft coating technique. J Surg Res. 1984;36:80–8.

    Article  CAS  Google Scholar 

  19. Tang Y, Singh J. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems. Int J Pharm. 2008;357:119–25.

    Article  CAS  Google Scholar 

  20. Cortizo MS, Alessandrini JL, Etcheverr SB, Cortizo AM. A vanadium/aspirin complex controlled release using a poly (β-propiolactone) film. Effects on osteosarcoma cells. J Biomater Sci Polym Ed 2001;12:945–59.

    Google Scholar 

  21. Yoon H, Kim G. A three-dimensional polycaprolactone scaffold combined with a drug delivery system consisting of electrospun nanofibers. J Pharm Sci. 2011;100:424–30.

    Article  CAS  Google Scholar 

  22. Del Gaudio C, Grigioni M, Bianco A, De Angelis G. Electrospun bioresorbable heart valve scaffold for tissue engineering. Int J Artif Organs. 2008;31:68–75.

    Google Scholar 

  23. Liu SJ, Chiang FJ, Hsiao CY, Kau YC, Liu KS. Fabrication of balloon-expandable self-lock drug-eluting polycaprolactone stents using micro-injection molding and spray coating techniques. Ann Biomed Eng. 2010;38:3185–94.

    Article  Google Scholar 

  24. Woodruff MA, Hutmacher DW. The return of a forgotten polymer—polycaprolactone in the 21st century. Prog Polym Sci. 2010;35:217–56.

    Article  Google Scholar 

  25. Lee SJ, Yoo JJ, Lim GJ, Atala A, Stitzel J. In vitro evaluation of electrospun nanofiber scaffolds for vascular graft application. J Biomed Mater Res A. 2007;83:999–1008.

    Google Scholar 

  26. McClure MJ, Sell SA, Ayres CE, Simpson DG, Bowlin GL. Electrospinning-aligned and random polydioxanone-polycaprolactone-silk fibroin-blended scaffolds: geometry for a vascular matrix. Biomed Mater. 2009;4:055010.

    Article  CAS  Google Scholar 

  27. Bakar SK, Niazi S. Stability of aspirin in different media. J Pharm Sci. 1983;72:1024–6.

    Article  CAS  Google Scholar 

  28. Wan LS, Xu ZK. Polymer surfaces structured with random or aligned electrospun nanofibers to promote the adhesion of blood platelets. J Biomed Mater Res A. 2009;89:168–75.

    Google Scholar 

  29. Yarin AL, Kataphinan W, Reneker DH. Branching in electrospinning of nanofibers. J Appl Phys. 2005;98:064501.

    Article  Google Scholar 

  30. Gentsch R, Boysen B, Lankenau A, Börner HG. Single-step electrospinning of bimodal fiber meshes for ease of cellular infiltration. Macromol Rapid Commun. 2010;31:59–64.

    Article  CAS  Google Scholar 

  31. Li WJ, Cooper JA Jr, Mauck RL, Tuan RS. Fabrication and characterization of six electrospun poly(α-hydroxy ester)-based fibrous scaffolds for tissue engineering applications. Acta Biomater. 2006;2:377–85.

    Article  Google Scholar 

  32. Kim JH, Kim SH, Kim HK, Akaike T, Kim SC. Adhesion and growth of endothelial cell on amphiphilic PU/PS IPN surface: effect of amphiphilic balance and immobilized collagen. J Biomed Mater Res A. 2002;62:613–21.

    Article  CAS  Google Scholar 

  33. Amornsakchai T, Cansfield DLM, Jawad SA, Pollard G, Ward IM. The relation between filament diameter and fracture strength for ultra-high-modulus polyethylene fibres. J Mater Sci. 1993;28:1689–98.

    Article  CAS  Google Scholar 

  34. Del Gaudio C, Fioravanzo L, Folin M, Marchi F, Ercolani E, Bianco A. Electrospun tubular scaffolds: on the effectiveness of blending poly(ε-caprolactone) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate). J Biomed Mater Res B. 2012;100B:1883–98.

    Google Scholar 

  35. Stankus JJ, Soletti L, Fujimoto K, Hong Y, Vorp DA, Wagner WR. Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials. 2007;28:2738–46.

    Article  CAS  Google Scholar 

  36. Donovan DL, Schmidt SP, Townshend SP, Njus GO, Sharp WV. Material and structural characterization of human saphenous vein. J Vasc Surg. 1990;12:531–7.

    CAS  Google Scholar 

  37. Lam CXF, Savalani MM, Teoh S, Hutmacher DW. Dynamics of in vitro polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions. Biomed Mater. 2008;3:1–15.

    Article  Google Scholar 

  38. Ritger PL, Peppas NA. A simple equation for description of solute release I. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. J Control Release. 1987;5:23–36.

    Article  CAS  Google Scholar 

  39. Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2001;48:139–57.

    Article  CAS  Google Scholar 

  40. Szentivanyi A, Chakradeo T, Zernetsch H, Glasmacher B. Electrospun cellular microenvironments: understanding controlled release and scaffold structure. Adv Drug Deliv Rev. 2011;63:209–20.

    Article  CAS  Google Scholar 

  41. Lao LL, Peppas NA, Boey FY, Venkatraman SS. Modeling of drug release from bulk-degrading polymers. Int J Pharm. 2011; 418:28–41.

    Article  CAS  Google Scholar 

  42. Hong Y, Ye SH, Nieponice A, Soletti L, Vorp DA, Wagner WR. A small diameter, fibrous vascular conduit generated from a poly(ester urethane)urea and phospholipid polymer blend. Biomaterials. 2009;30:2457–67.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank the Cord Blood Bank, Department of Hematology, University Hospital Careggi, Florence, for kindly providing the cord blood samples. CDG acknowledges the Italian Interuniversity Consortium on Materials Science and Technology (INSTM) for the financial support of the scientific activity, Co-funded Grant “Progettazione, realizzazione e caratterizzazione funzionale di scaffold polimerici elettrofilati per l’ingegneria del tessuto cardiovascolare”.

Author information

Authors and Affiliations

  1. Department of Industrial Engineering, University of Rome “Tor Vergata”, INSTM Research Unit Roma Tor Vergata, Via del Politecnico 1, 00133, Rome, Italy

    Costantino Del Gaudio, Enrico Ercolani & Alessandra Bianco

  2. Department of Chemical Science and Technology, University of Rome “Tor Vergata”, Via della Ricerca Scientifica, 00133, Rome, Italy

    Pierluca Galloni & Federico Santilli

  3. BIOAIRLab, European Center of Thoracic Research (CERT), University Hospital Careggi, Florence, Italy

    Silvia Baiguera & Leonardo Polizzi

Authors
  1. Costantino Del Gaudio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Enrico Ercolani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pierluca Galloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Federico Santilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvia Baiguera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Leonardo Polizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alessandra Bianco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Costantino Del Gaudio or Alessandra Bianco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Del Gaudio, C., Ercolani, E., Galloni, P. et al. Aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds: potential small-diameter vascular grafts for thrombosis prevention. J Mater Sci: Mater Med 24, 523–532 (2013). https://doi.org/10.1007/s10856-012-4803-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-012-4803-3

Keywords

Search

Navigation