Tunable Elastomers with an Antithrombotic Component for Cardiovascular Applications

Abstract

This study reports the development of a novel family of biodegradable polyurethanes for use as tissue engineered cardiovascular scaffolds or blood-contacting medical devices. Covalent incorporation of the antiplatelet agent dipyridamole into biodegradable polycaprolactone-based polyurethanes yields biocompatible materials with improved thromboresistance and tunable mechanical strength and elasticity. Altering the ratio of the dipyridamole to the diisocyanate linking unit and the polycaprolactone macromer enables control over both the drug content and the polymer cross-link density. Covalent cross-linking in the materials achieves significant elasticity and a tunable range of elastic moduli similar to that of native cardiovascular tissues. Interestingly, the cross-link density of the polyurethanes is inversely related to the elastic modulus, an effect attributed to decreasing crystallinity in the more cross-linked polymers. In vitro characterization shows that the antiplatelet agent is homogeneously distributed in the materials and is released slowly throughout the polymer degradation process. The drug-containing polyurethanes support endothelial cell and vascular smooth muscle cell proliferation, while demonstrating reduced levels of platelet adhesion and activation, supporting their candidacy as promising substrates for cardiovascular tissue engineering.

Use of 3D Printing for the Development of Biodegradable Antiplatelet Materials for Cardiovascular Applications

“…These applications include the production of vascular grafts, stents or even cardiac valves [ 1 , 2 , 3 , 4 ]. Conventional polymers used for this purpose are polytetrafluoroethylene (PTFE) and poly(ethylene terephthalate) (PET) [ 5 , 6 , 7 ]. These non-biodegradable polymers have shown excellent properties to be used as vascular grafts with diameters larger than 6 mm [ 5 ].…”

“…Conventional polymers used for this purpose are polytetrafluoroethylene (PTFE) and poly(ethylene terephthalate) (PET) [ 5 , 6 , 7 ]. These non-biodegradable polymers have shown excellent properties to be used as vascular grafts with diameters larger than 6 mm [ 5 ]. However, higher rates of occlusion were reported for small diameter vascular grafts prepared using these types of polymers [ 5 ].…”

“…These non-biodegradable polymers have shown excellent properties to be used as vascular grafts with diameters larger than 6 mm [ 5 ]. However, higher rates of occlusion were reported for small diameter vascular grafts prepared using these types of polymers [ 5 ]. In order to solve some of the limitations presented by polymeric materials, drugs can be added to obtain polymeric devices with enhanced properties.…”

“…In order to solve some of the limitations presented by polymeric materials, drugs can be added to obtain polymeric devices with enhanced properties. Drugs such as antibiotics, anticancer drugs or anticoagulant agents, among many others, were combined with polymers for this purpose [ 1 , 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The combination of antibiotics and polymers has been extensively studied for the development of anti-infective materials [ 16 , 17 , 18 ].…”

Synthetic and Bone tissue engineering graft substitutes: What is the future?

“…Elastomers are polymers that possess viscoelasticity, allowing them to withstand more repetitive strain and cyclic stress com- pared to other materials [52] . Elastomer grafts provide a surface for cell adhesion, cell integration, and proliferation within graft tissue, ultimately allowing substitution of graft with host vascular tissue.…”