Development of drug loaded cardiovascular prosthesis for thrombosis prevention using 3D printing

Juan Domínguez-Robles,Tingjun Shen,Victoria A Cornelius,Francesca Corduas,Elena Mancuso,Ryan F Donnelly,Andriana Margariti,Dimitrios A Lamprou,Eneko Larrañeta

doi:10.1016/j.msec.2021.112375

Juan Domínguez-Robles, Tingjun Shen + Show 7 more

Open Access

https://doi.org/10.1016/j.msec.2021.112375

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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.

Highlights

Cardiovascular disease (CVD) is a general term used for conditions affecting the heart or blood vessels
3D printing was used to prepare vascular grafts using the higher DIP concentration (20% w/w) as preliminary work on DIP loaded materials suggested that higher DIP loadings ranging between 15 and 20% pro vided the best antiplatelet effect [21]
This can be corroborated by microscopy (Fig. 2B–F) which shows the drug compound (DIP) was dissolved within the PCL matrix, as the vascular grafts and their cross sections were completely homogeneous, showing no visible DIP aggregates

Summary

Introduction

Cardiovascular disease (CVD) is a general term used for conditions affecting the heart or blood vessels. The main types of CVDs include ischemic heart disease, heart failure, peripheral arterial disease and stroke [1]. CVDs remain the leading causes of death globally and represent a main contributor to reduced quality of life [2,3]. Quick restoration of tissue perfusion is a key factor to prevent heart failures in people suffering from coronary heart disease and for supporting the repair of ischemic limbs. Revascularization techniques include angio plasty, placement of a stent, or surgical bypass grafting [6]. For the latter technique, autologous vessels remain the best clinical option, but the process of harvesting vessels is invasive, and they are often unsuitable [7,8,9]. Synthetic vascular grafts made from biocompatible materials are still needed [1,6]

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