| Summary: |
There is a clear lack of biomaterials with suitable hemocompatibility to apply as blood contacting devices (BCD). Materials currently available to develop BCD in long-term applications (silicone, polypropylene, polyethylene, terephthalate, Polyvinylchloride, etc.) are associated with several complications such as hemolysis, thrombosis, infection and fibrous tissue formation. These failure causes have high impact on the quality of life and survival of patients and in economy due to associated costs. Every year, just in USA and Europe, there are 1.8 million patients that need arterial prostheses, reflecting an annual cost of more than 25 billion euros. To date, there is not a vascular graft with capacity to replace efficiently small diameter vessels (ID<6mm), with available grafts being associated with unacceptable patency rates (<25% at 3 years) due to above mentioned complications. Thus, there is an urgent need to develop new biomaterials that match the performance of native small diameter vessels. This project aims to develop novel biomaterials with appropriate hemocompatible properties to apply in the design of blood contacting devices. More specifically, we aim to explore materials that are described to have good hemo/biocompatibility, but which are not applied as BCD due to weak mechanical properties. As such, we propose the incorporation of graphene-based materials (GBMs) to tune the mechanical properties of such biomaterials for application as small-diameter vascular grafts. Two approaches will be followed, making use of different biomaterials. In the first approach, GBMs will be incorporated in hydrogels. The mechanical properties, hemocompatibility, biocompatibility and antimicrobial activity of GBMs/hydrogels will be assessed and the ones with appropriate features will be selected to optimize the fabrication of 3D tubular small diameter vascular grafts using two different technologies, namely co-axial extrusion and 3D printing. Depending on the capacity  |
Summary
There is a clear lack of biomaterials with suitable hemocompatibility to apply as blood contacting devices (BCD). Materials currently available to develop BCD in long-term applications (silicone, polypropylene, polyethylene, terephthalate, Polyvinylchloride, etc.) are associated with several complications such as hemolysis, thrombosis, infection and fibrous tissue formation. These failure causes have high impact on the quality of life and survival of patients and in economy due to associated costs. Every year, just in USA and Europe, there are 1.8 million patients that need arterial prostheses, reflecting an annual cost of more than 25 billion euros. To date, there is not a vascular graft with capacity to replace efficiently small diameter vessels (ID<6mm), with available grafts being associated with unacceptable patency rates (<25% at 3 years) due to above mentioned complications. Thus, there is an urgent need to develop new biomaterials that match the performance of native small diameter vessels. This project aims to develop novel biomaterials with appropriate hemocompatible properties to apply in the design of blood contacting devices. More specifically, we aim to explore materials that are described to have good hemo/biocompatibility, but which are not applied as BCD due to weak mechanical properties. As such, we propose the incorporation of graphene-based materials (GBMs) to tune the mechanical properties of such biomaterials for application as small-diameter vascular grafts. Two approaches will be followed, making use of different biomaterials. In the first approach, GBMs will be incorporated in hydrogels. The mechanical properties, hemocompatibility, biocompatibility and antimicrobial activity of GBMs/hydrogels will be assessed and the ones with appropriate features will be selected to optimize the fabrication of 3D tubular small diameter vascular grafts using two different technologies, namely co-axial extrusion and 3D printing. Depending on the capacity of these new composites to either adhere or repel protein adsorption and cell adhesion and proliferation, they will be used to pursue a non-fouling or tissue engineering strategy.
In the second approach, GBMs will be incorporated in decellularized matrix of blood vessels from human placenta to improve their mechanical properties in order to generate a cell-free matrix with capacity to replace a native blood vessel and induce endothelization pos-implantation. Also, and since it is expected that GBMs are exposed in the lumen of the decellularized vessel, GBMs functionalization with anticoagulant and pro-endothelization factors will be performed to further improve graft performance.
Developed vascular grafts with most promising characteristics will be implanted in vivo in a rat model to evaluate the patency and the host response to the new biomaterials.
The biomaterials developed during this project are expected to stand as a breakthrough in the design of small diameter vascular grafts. |