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Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing
Juan Domínguez-Robles1, Tingjun Shen1, Victoria A Cornelius2
1School of Pharmacy, Queen's University Belfast, Lisburn Road 97, Belfast BT9 7BL, UK.
Insights
3D printed vascular grafts loaded with dipyridamole (DIP) offer a promising solution for cardiovascular disease. These biodegradable grafts demonstrate sustained drug release, reduced platelet deposition, and excellent cytocompatibility, improving patient outcomes.
Area of Science:
- Biomaterials Science
- Cardiovascular Engineering
- Drug Delivery Systems
Background:
- Cardiovascular disease (CVD) is a leading global cause of mortality, necessitating improved tissue perfusion strategies.
- Current revascularization techniques face limitations, particularly the scarcity of suitable autologous vessels for bypass grafting.
- There is a critical need for synthetic vascular grafts with enhanced antithrombotic and endothelialization properties.
Purpose of the Study:
- To develop and characterize 3D printed biodegradable vascular grafts incorporating dipyridamole (DIP).
- To evaluate the drug release kinetics, antiplatelet efficacy, and cytocompatibility of these novel grafts.
Main Methods:
- Polycaprolactone (PCL) and DIP were blended without solvents and 3D printed into vascular grafts.
- A mixture of high and low molecular weight PCL was used to optimize DIP integration.
- Graft characterization involved multiple techniques, including drug release, antiplatelet assays, and cytocompatibility testing.
Main Results:
- DIP was successfully integrated within the PCL matrix, exhibiting sustained and linear drug release over 30 days without initial burst release.
- DIP-loaded grafts significantly reduced platelet deposition compared to PCL-only grafts.
- Hemolysis percentages were below 4% for both PCL and PCL with 20% DIP grafts, indicating good hemocompatibility. Grafts supported cellular attachment, viability, and growth.
Conclusions:
- 3D printed DIP-loaded PCL vascular grafts represent a viable alternative to autologous vessels.
- These grafts demonstrate excellent antithrombotic properties and biocompatibility, crucial for preventing graft failure.
- The developed technology offers customizable vascular graft fabrication with controlled drug delivery for improved cardiovascular treatments.
Abstract:
Cardiovascular disease (CVD) is a general term for conditions which are the leading cause of death in the world. Quick restoration of tissue perfusion is a key factor to combat these diseases and improve the quality and duration of patients' life. Revascularization techniques include angioplasty, placement of a stent, or surgical bypass grafting. For the latter technique, autologous vessels remain the best clinical option; however, many patients lack suitable autogenous due to previous operations and they are often unsuitable. Therefore, synthetic vascular grafts providing antithrombosis, neointimal hyperplasia inhibition and fast endothelialization are still needed. To address these limitations, 3D printed dipyridamole (DIP) loaded biodegradable vascular grafts were developed. Polycaprolactone (PCL) and DIP were successfully mixed without solvents and then vascular grafts were 3D printed. A mixture of high and low molecular weight PCL was used to better ensure the integration of DIP, which would offer the biological functions required above. Moreover, 3D printing technology provides the ability to fabricate structures of precise geometries from a 3D model, enabling to customize the vascular grafts' shape or size. The produced vascular grafts were fully characterized through multiple techniques and the last step was to evaluate their drug release, antiplatelet effect and cytocompatibility. The results suggested that DIP was properly mixed and integrated within the PCL matrix. Moreover, these materials can provide a sustained and linear drug release without any obvious burst release, or any faster initial release rates for 30 days. Compared to PCL alone, a clear reduced platelet deposition in all the DIP-loaded vascular grafts was evidenced. The hemolysis percentage of both materials PCL alone and PCL containing 20% DIP were lower than 4%. Moreover, PCL and 20% DIP loaded grafts were able to provide a supportive environment for cellular attachment, viability, and growth.