Clopidogrel-loaded vascular grafts prepared using digital light processing 3D printing

Drug Deliv Transl Res. 2024 Jun;14(6):1693-1707. doi: 10.1007/s13346-023-01484-8. Epub 2023 Dec 5.

Abstract

The leading cause of death worldwide and a significant factor in decreased quality of life are the cardiovascular diseases. Endovascular operations like angioplasty, stent placement, or atherectomy are often used in vascular surgery to either dilate a narrowed blood artery or remove a blockage. As an alternative, a vascular transplant may be utilised to replace or bypass a dysfunctional or blocked blood vessel. Despite the advancements in endovascular surgery and its popularisation over the past few decades, vascular bypass grafting remains prevalent and is considered the best option for patients in need of long-term revascularisation treatments. Consequently, the demand for synthetic vascular grafts composed of biocompatible materials persists. To address this need, biodegradable clopidogrel (CLOP)-loaded vascular grafts have been fabricated using the digital light processing (DLP) 3D printing technique. A mixture of polylactic acid-polyurethane acrylate (PLA-PUA), low molecular weight polycaprolactone (L-PCL), and CLOP was used to achieve the required mechanical and biological properties for vascular grafts. The 3D printing technology provides precise detail in terms of shape and size, which lead to the fabrication of customised vascular grafts. The fabricated vascular grafts were fully characterised using different techniques, and finally, the drug release was evaluated. Results suggested that the performed 3D-printed small-diameter vascular grafts containing the highest CLOP cargo (20% w/w) were able to provide a sustained drug release for up to 27 days. Furthermore, all the CLOP-loaded 3D-printed materials resulted in a substantial reduction of the platelet deposition across their surface compared to the blank materials containing no drug. Haemolysis percentage for all the 3D-printed samples was lower than 5%. Moreover, 3D-printed materials were able to provide a supportive environment for cellular attachment, viability, and growth. A substantial increase in cell growth was detected between the blank and drug-loaded grafts.

Keywords: 3D printing; Clopidogrel; Digital light processing; Vascular grafts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessel Prosthesis*
  • Clopidogrel* / administration & dosage
  • Clopidogrel* / chemistry
  • Drug Liberation
  • Humans
  • Platelet Aggregation Inhibitors* / administration & dosage
  • Platelet Aggregation Inhibitors* / chemistry
  • Platelet Aggregation Inhibitors* / pharmacology
  • Polyesters* / chemistry
  • Polyurethanes / chemistry
  • Printing, Three-Dimensional*

Substances

  • Clopidogrel
  • Polyesters
  • Platelet Aggregation Inhibitors
  • polycaprolactone
  • poly(lactide)
  • Polyurethanes