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Fabrication of Engineered Vascular Flaps Using 3D Printing Technologies
Published on: May 19, 2022
Clopidogrel-loaded vascular grafts prepared using digital light processing 3D printing
Masoud Adhami1, Camila J Picco1, Usanee Detamornrat1
1School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, Northern Ireland, UK.
Insights
Biodegradable 3D-printed vascular grafts loaded with clopidogrel (CLOP) show sustained drug release for 27 days, reducing platelet deposition and promoting cell growth for improved cardiovascular treatments.
Area of Science:
- Biomaterials Science
- Cardiovascular Engineering
- 3D Printing Technology
Background:
- Cardiovascular diseases are a leading cause of mortality worldwide, necessitating effective vascular replacement or bypass strategies.
- While endovascular techniques have advanced, vascular bypass grafting remains crucial for long-term revascularization, driving demand for biocompatible synthetic grafts.
- Existing synthetic grafts face challenges in meeting the complex mechanical and biological requirements for vascular repair.
Purpose of the Study:
- To develop and characterize biodegradable clopidogrel (CLOP)-loaded vascular grafts using digital light processing (DLP) 3D printing.
- To evaluate the mechanical properties, drug release kinetics, hemocompatibility, and cellular interactions of the fabricated grafts.
- To assess the efficacy of CLOP-loaded grafts in reducing platelet deposition and promoting cell viability and growth.
Main Methods:
- Fabrication of vascular grafts using DLP 3D printing with a blend of polylactic acid-polyurethane acrylate (PLA-PUA) and low molecular weight polycaprolactone (L-PCL).
- Incorporation of clopidogrel (CLOP) at varying concentrations into the graft material.
- Comprehensive characterization including mechanical testing, drug release studies, haemolysis assays, and cell culture experiments (attachment, viability, growth).
Main Results:
- 3D-printed vascular grafts demonstrated sustained clopidogrel release for up to 27 days, particularly with 20% (w/w) CLOP loading.
- CLOP-loaded grafts significantly reduced platelet deposition compared to unloaded controls.
- All tested 3D-printed materials exhibited low haemolysis (<5%) and supported cellular attachment, viability, and proliferation, with enhanced cell growth observed in drug-loaded grafts.
Conclusions:
- DLP 3D printing enables the fabrication of customized, biodegradable vascular grafts with tailored mechanical and biological properties.
- The developed CLOP-loaded vascular grafts offer promising hemocompatibility and sustained drug delivery, potentially reducing thrombotic events.
- These 3D-printed grafts provide a supportive scaffold for cell integration, indicating their potential for advanced cardiovascular applications.
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.
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